The role of viruses in human infectious pathology

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Introduction

Viral infections represent one of the major threats to public health worldwide. They have a significant impact on human life expectancy and quality of life, and also impose a serious economic burden on nations. On a global scale, the pathogens of two main groups are of primary importance to humanity: anthroponoses and zoonoses with pandemic spread (influenza and acute respiratory viral infections (ARVI), coronaviruses, acute intestinal infections, human immunodeficiency virus (HIV), parenteral hepatitis, parvovirus, papillomavirus, herpesvirus, and poliovirus infections) and zoonoses, of which the most damaging are vector-borne "mosquito" fevers (dengue, yellow fever, chikungunya, Zika, West Nile), as well as numerous infections transmitted by ticks, mosquitoes, and midges. Zoonotic hemorrhagic fevers transmitted by direct contact, such as Ebola, Marburg, and Nipah fevers, New and Old World arenavirus fevers, and poxviruses, remain extremely relevant. According to rough estimates, more than 7 billion people worldwide are infected with viral infections annually – that is, virtually the entire global population – with the majority of cases involving various forms of acute respiratory infections (6 billion), seasonal influenza and acute respiratory viral infections (1–5 billion people per year), tropical fevers (about 450 million infections), new cases of parenteral hepatitis (3 million), and HIV (1.5 million infections). In addition, herpes, papilloma, and polioviruses – along with the associated cancers and other systemic diseases – are widespread. Annual mortality from viral infections of all types reaches 10–15 million people, excluding long-term health consequences, related complications, and reductions in life expectancy and quality of life. These statistics must be supplemented by the millions of patients dying from cancers, central nervous system (CNS) diseases, cardiovascular diseases, and diseases of the liver and gastrointestinal (GI) tract, triggered by various viral infections that act as a trigger for the pathological process or exacerbation of its chronic course^{1, 2}.

Viral infections cause enormous economic damage, both in the form of direct treatment costs and as a result of lost workdays, reduced productivity, and other factors. According to research by the World Bank (2020), the direct and indirect economic losses from just a few viral infections (influenza, HIV, hepatitis, dengue, etc.) can range from $500 billion to $1 trillion annually. The emergence of new epidemic and pandemic pathogens, such as new strains of influenza or the SARS-CoV-2 coronavirus, causes even greater damage. According to United Nations estimates, the COVID-19 pandemic has caused global losses to the world economy estimated at $8.8 trillion, and long-term losses could reach $16 trillion (10–15% of global GDP) [1].

All organisms serve as hosts for viruses. The global viral pan-genome contains approximately 10¹⁰ genes [2]. It is now firmly established that viruses are ubiquitous across all three domains of the biosphere: archaea, bacteria, and eukaryotes. Moreover, the coevolution of viruses with their hosts has continued for over 3.9 billion years since the emergence of the last universal common ancestor (LUCA) of archaea and bacteria, long before the appearance of the eukaryotic cell. All major biogeochemical processes were carried out by prokaryotes – archaea and bacteria [2–4]. LUCA presumably already possessed a virome including the ancestors of modern tailed phages and viruses with a major capsid protein featuring a single or double β-barrel fold [5]. Thus, the emergence of viruses occurred prior to the existence of LUCA and eukaryogenesis, which took place approximately 1.8 billion years ago [5, 6].

The first eukaryotic cells arose through endosymbiosis between archaea (Asgardarchaeota kingdom) and eubacteria from the α-proteobacteria group — the ancestors of mitochondria. The prokaryotic viruses that existed at that time became the ancestors of eukaryotic viruses. As new eukaryotic taxa emerged, their representatives became hosts to various viruses (Figure) [2, 3, 7–10]. With the evolution of the biosphere over hundreds of millions of years, viruses became involved in interpopulation interactions with eukaryotes – protozoa, algae, fungi, plants, invertebrates, and vertebrates, including primates (Paleocene – 70 million years ago – the golden age of mammals), specifically with hominids (Pliocene – 6–2.5 million years ago), hominins (Pleistocene – 5–1 million years ago), and Homo sapiens (300–50 thousand years ago). It was only in the last 10,000 years, as a result of animal domestication, the colonization of rodent populations in human dwellings, and the formation of civilizations, that conditions arose for the interaction between human and animal viral gene pools. These processes were accompanied (and continue to be accompanied today) by the emergence of zoonotic outbreaks, followed by the transition of a number of pathogens from the category of zoonotic to that of zoanthroponotic and anthroponotic [7].

 

Figure. The domains of the biosphere and their approximate time of origin.

Рисунок. Домены биосферы с указанием приблизительного времени их появления.

 

Over the past century, the state of the biosphere has undergone significant changes due to human activity. The total mass of anthropogenic origin currently exceeds the total global biomass of all organisms at any given moment [11]. Viruses can have a significant impact on global processes within the biosphere and beyond by affecting humanity and its economic and other activities. For example, observations using spacecraft have shown a noticeable decrease in nighttime temperatures on the Moon's surface during the COVID-19 pandemic, which the authors attribute to a decrease in Earth's albedo due to reduced anthropogenic emissions that enhance cloud formation [12].

Thus, viruses are one of the oldest components of the biosphere's biogeochemical and genetic machinery, involved in the interaction and regulation of other components, primarily prokaryotic and eukaryotic organisms. The global virome (or virosphere, domain Viraea) is a controlling hub that, despite having minimal biomass of its own, influences far more significant flows of matter and energy. The virosphere, through constant changes in its population gene pools, not only demonstrates adaptation to environmental conditions but also contributes to the variability of other domains of the biosphere, participating in the formation of its biological diversity [7].

The spectrum of known viral pathogens causing human infections encompasses at least 500 different viruses, taxonomically classified into more than 180 genera. Virus taxonomy/megataxonomy has continued to evolve in recent years, and many taxonomic ranks continue to be revised in light of new research [2, 3]. The Table lists virtually all known human pathogens, indicating the corresponding nosology and presenting their current taxonomic status.

 

Table. Taxonomic classification of human viruses and their contribution to infectious disease pathogenesis

Таблица. Таксономическое положение вирусов, инфицирующих человека, и их роль в инфекционной патологии

1	2	3	4	5	6	7	8	9	10	11
Realm (Надцарство)	Kingdom (Царство)	Phylum (Тип)	Class (Класс)	Order (Отряд)	Family (Семейство)	Subfamily (Подсемейство)	Genus (Род)	Species (Вид)	Virus names used in clinical practice (Названия вирусов, используемые в клинической практике)	Infection, pathology (Инфекция, патология)
Duplodnaviria	Heunggongvirae	Peploviricota	Herviviricetes	Herpesvirales	Orthoherpesviridae	Alphaherpesvirinae	Simplexvirus	S. humanalpha1	Human herpesvirus 1 (HHV-1)	Oral herpes (HSV-1) and genital herpes (HSV-2). A centuries-long pantropic pandemic with a global prevalence ranging from 40% to 100% of the population. These viruses exhibit systemic, lymphoproliferative, and neuropathogenic properties and act as immunosuppressive agents. They establish lifelong persistence and, upon reactivation, can lead to pronounced productive clinical manifestations, including meningoencephalitis, keratitis, hepatitis, and pancreatitis. Due to their immunosuppressive effects, they may contribute to immune system dysregulation and are potentially involved in aging processes. Associations have also been suggested with Alzheimer's disease
								S. humanalpha2	Human herpesvirus 1 (HHV-1)
							Varicellovirus	V. humanalpha3	Varicella-zoster virus (VZV, HHV-3)	Global distribution (pandemic). Varicella (primary infection acquired exogenously via the respiratory route) and herpes zoster (resulting from endogenous reactivation). Clinical manifestations include exanthema and, in some cases, encephalitis
						Betaherpesvirinae	Cytomegalovirus	C. humanbeta5	Human cytomegalovirus (HCMV), Human herpesvirus 5 (HHV-5)	Cytomegalovirus infection is characterized by broad tissue tropism and a wide spectrum of clinical manifestations involving multiple organs and systems. These include hepatomegaly, splenomegaly, lymphadenopathy (CMV-associated mononucleosis, CMV hepatitis), as well as congenital abnormalities when infection occurs during pregnancy. Global distribution (pandemic)
							Roseolovirus	R. humanbeta6a	Human herpesvirus type 6A (HHV-6A)	Neonatal exanthema. Mononucleosis-like syndrome.
								R. humanbeta6B	Human herpesvirus type 6B (HHV-6B)	Chronic fatigue syndrome with persistent lymphadenopathy
								R. humanbeta7	Human herpesvirus type 7 (HHV-7)	Chronic fatigue syndrome associated with disturbances in both mental and somatic status, including low-grade fever, sleep disturbances, fatigue, lymphadenopathy, and muscle weakness
						Gammaherpesvirinae	Lymphocryptovirus	L. humangamma4	Epstein–Barr virus (EBV, HHV-4)	Epstein–Barr virus infection is associated with infectious mononucleosis, nasopharyngeal carcinoma, Burkitt lymphoma, and multiple sclerosis
							Rhadinovirus	Rh. humangamma8	Kaposi's sarcoma-associated herpesvirus (HHV-8)	Kaposi sarcoma
Floreoviria	Shotokuvirae	Commensaviricota	Cardeaviricetes	Sanitavirales	Anelloviridae		Alphatorquevirus	A. homin1–31	Torque teno virus (TTV)	Global prevalence, with infection rates reaching up to 90% of the population. The virus can be isolated from plasma, saliva, and feces. Potential associations have been suggested with liver diseases, respiratory disorders, hematological conditions, and malignancies
							Betatorquevirus	B. homini1–38	Torque teno mini virus (TTMV)
							Gammatorquevirus	G. homidi1–15	Torque teno midi virus (TTMDV)
		Cossaviricota	Papovaviricetes	Sepolyvirales	Polyomaviridae		Alphapolyomavirus	A. quintihominis	Polyomavirus 5 (MCPyV)	Global distribution (centuries-long pandemic). Associated with progressive multifocal leukoencephalopathy, hemorrhagic cystitis, brain tumors, and renal involvement, particularly in immunocompromised patients following organ transplantation (BK and JC viruses). These viruses establish lifelong persistence in the tonsils, lower urinary tract, and bone marrow
								A. octihominis	Polyomavirus 8 (TSPyV)
								A. nonihominis	Polyomavirus 9 (HPyV9)
								A. terdecihominis	Polyomavirus 13 (NJPyV)
							Betapolyomavirus	B. hominis	BK polyomavirus (BKPyV)
								B. secuhominis	JC polyomavirus (JCPyV)
								B. tertihominis	Polyomavirus 3 (KIPyV)
								B. quartihominis	Polyomavirus 4 (WUPyV)
							Deltapolyomavirus	D. sextihominis	Polyomavirus 6 (HPyV6)
								D. septihominis	Polyomavirus 7 (HPyV7)
								D. decihominis	Polyomavirus 10 (MWPyV)
								D. undecihominis	Polyomavirus 11 (STLPyV)
				Zurhausenvirales	Papillomaviridae	Firstpapillomavirinae	Alphapapillomavirus	Alphapapillomavirus 1–11, 13, 14	Human papillomavirus types 2, 3, 6, 7, 10, 11, 13, 16, 18, 26–35, 39, 40, 42–45, 51–54, 56–59, 61, 62, 66–74, 77, 78, 81–87, 89, 90, 91, 94, 97, 102, 106, 114, 117, 125, 160	Global distribution (centuries-long pandemic). Chronic epidermal lesions, oropharyngeal carcinoma and other malignancies, condylomatosis, cervical cancer, cutaneous warts, conjunctival papillomas, and other manifestations
							Betapapillomavirus	Betapapillomavirus 1–5	Human papillomavirus types 5, 8, 9, 12, 14, 15, 17, 19–25, 36–38, 47, 49, 75, 76, 80, 92, 93, 96, 98–100, 104, 105, 107, 110, 111, 113, 115, 118, 120, 122, 124, 143, 145, 150–152, 159, 174
							Gammapapillomavirus	Gammapapillomavirus 1–27	Human papillomavirus types 4, 48, 50, 60, 65, 88, 95, 101, 103, 108, 109, 112, 116, 119, 121, 123, 126–142, 144, 146–149, 153–158, 161–173, 175, 178–180, 184, 187, 197, 199–202, 205
Floreoviria	Shotokuvirae	Cossaviricota					Mupapillomavirus	Mupapillomavirus 1–3	Human papillomavirus types 1, 63, 204
							Nupapillomavirus	Nupapillomavirus 1	Human papillomavirus type 41
			Quintoviricetes	Piccovirales	Parvoviridae	Parvovirinae	Bocaparvovirus	B. primate1	Human bocavirus 1 and 3 (HBoV1, HBoV3)	Seasonal acute respiratory infection (~ 1% annually), gastroenteritis, global distribution (~ 5% of all acute respiratory infections; ~ 0.6% of the total population)
								B. primate2	Human bocavirus 2c and 4 (HBoV2c, HBoV4)
							Erythroparvovirus	E. primate1	Human parvovirus B19 (B19V)	Pediatric exanthematous diseases, arthropathy, chronic hemolytic anemia, non-immune hydrops fetalis, arthralgia, and arthritis
							Protoparvovirus	P. primate1	Bufavirus 1a (BuV1a)	A recently identified and insufficiently studied human virus, detected in stool samples, predominantly in children with diarrhea
								P. primate3	Cutavirus (CuV)	A novel, poorly characterized human virus identified in biopsies of cutaneous T-cell lymphomas; also detected in children with diarrhea, as well as in blood and stool samples of asymptomatic individuals
							Tetraparvovirus	T. primate1	Human parvovirus 4 (PARV4)	Detected in the blood of patients with HIV and hepatitis C virus infection, injection drug users, and individuals with hemophilia. Clinical manifestations remain poorly defined but may include fever, night sweats, headache, and diarrhea
		Cressdnaviricota	Arfiviricetes	Cirlivirales	Circoviridae		Circovirus	C. human	Human circovirus 1 (HumCV1)	Viruses pathogenic for pigs and birds, with potential zoonotic transmission to humans
							Cyclovirus	C. manukha	Human associated cyclovirus 3	Cycloviruses have been detected in human feces, cerebrospinal fluid, blood, and other biological samples. Their pathogenicity in humans remains under investigation
								C. bashri	Human associated cyclovirus 4
								C. homa	Human associated cyclovirus 5
								C. mmadu	Human associated cyclovirus 6
								C. mutum	Human associated cyclovirus 7
								C. nhanloai	Human associated cyclovirus 8
								C. munthu	Human associated cyclovirus 9
								C. humana	Human associated cyclovirus 10
								C. manitan	Human associated cyclovirus 11
								C. manusyan	Human associated cyclovirus 12
				Recrevirales	Redondoviridae		Torbevirus	T. brisa	Human respiratory-associated brisavirus	Viruses identified in the upper and lower respiratory tract, as well as in stool samples. Their pathogenic role is unclear; they may represent components of the normal human virome (possibly associated with amoebae)
								T. viento	Human lung- or gut-associated vientovirus
Varidnaviria	Bamfordvirae	Nucleocytoviricota	Pokkesviricetes	Chitovirales	Poxviridae	Chordopoxvirinae	Molluscipoxvirus	M. molluscum	Molluscum contagiosum virus (MCV)	Cutaneous infection characterized by the appearance of small papules filled with clear fluid. Most commonly observed in children and immunocompromised patients
							Orthopoxvirus	O. variola	Variola virus (VARV)	Smallpox caused devastating global epidemics, with total mortality estimated at over 500 million people
								O. vaccinia	Vaccinia virus (VACV)	Vaccinia virus produces a mild infection in humans while conferring durable immunity against related orthopoxviruses
								O. monkeypox	Monkeypox virus (MPXV)	Monkeypox is associated with epidemic outbreaks worldwide
								O. cowpox	Cowpox virus (CPXV)	Cowpox occurs sporadically
								O. camelpox	Camelpox virus (CMLV)	Rare cases of human infection have been reported in individuals in contact with animals (e.g., camels); the infection is typically mild
								O. volepox	Rodentpox virus	Occurs sporadically
							Parapoxvirus	P. orf	Orf virus (ORFV)	"Orf" (contagious ecthyma), also referred to as "sheep/goat pox," presents as oropharyngeal dermatitis
								P. pseudocowpox	Pseudocowpox virus (PCPV)	A localized cutaneous infection known as "milker's nodules"
							Yatapoxvirus	Y. tanapox	Tanapox virus (TANV)	Sporadic cases have been reported in Equatorial Africa and in laboratory-associated infections
		Preplasmiviricota	Pharingeaviricetes	Rowavirales	Adenoviridae		Mastadenovirus	M. caesari	Human adenovirus 1, 2, 5, 6	Seasonal acute respiratory infection with global distribution (~ 7.5% of all acute respiratory infections; ~ 0.9% of the total population)
								M. blackbeardi	Human adenovirus 3, 7, 11, 14, 16, 21, 34, 35, 50, 55
								M. dominans	Human adenovirus 8, 9, 10, 13, 15, 17, 19, 20, 22–30, 32, 33, 37–39, 42–49, 51, 53, 54
								M. exoticum	Human adenovirus 4
								M. adami	Human adenovirus 12, 18, 31
								M. faecale	Human adenovirus 40, 41
								M. russelli	Human adenovirus 52
Riboviria	Orthornavirae	Duplornaviricota	Resentoviricetes	Reovirales	Sedoreoviridae		Orbivirus	O. magninsulae	Kemerovo virus (KEMV)	Epidemic outbreaks and sporadic cases in Western Siberia. The principal vector is the tick Ixodes persulcatus
							Rotavirus	R. alphagastroenteritidis	Human rotavirus (HRV)	Seasonal gastroenteritis with global distribution, particularly among children. Accounts for up to 90% of seasonal gastroenteritis cases (20–50% among hospitalized patients). Approximately 18 million cases occur annually, with up to 1 million deaths
							Coltivirus	C. dermacentoris	Colorado tick fever virus (CTFV)	Colorado tick fever (USA, Canada): characterized by febrile illness, occasionally complicated by meningoencephalitis, orchitis, hemorrhagic syndrome, and myocarditis. Primary vector: tick Dermacentor andersoni
								C. ixodis	Eyach virus (EYAV)	Sporadic cases reported in Germany and France, presenting with fever and neurological symptoms
		Kitrinoviricota	Alsuviricetes	Hepelivirales	Hepeviridae	Orthohepevirinae	Paslahepevirus	P. balayani	Hepatitis E virus (HEV)	Hepatitis E: global distribution with seasonal epidemic outbreaks. Mortality among pregnant women reaches 13–20%, compared to approximately 1% in the general population. Transmission occurs primarily via the fecal–oral route, most commonly through contaminated water
					Matonaviridae		Rubivirus	R. rubellae	Rubella virus (RuV)	Rubella: cyclical epidemics among children, accounting for 15–27% of cases in the overall disease structure
				Martellivirales	Togaviridae		Alphavirus	A. chikungunya	Chikungunya virus (CHIKV)	Epidemic outbreaks in temperate regions (e.g., Karelian fever), as well as in subtropical, tropical, subequatorial, and equatorial regions (including Chikungunya, O'nyong-nyong, Venezuelan, Western, and Eastern equine encephalitis, Ross River fever, etc.). Mortality rates range from 0.5% to 75%, depending on the pathogen
								A. sindbis	Sindbis virus (SINV)
								A. western	Western equine encepha-litis virus (WEEV)
								A. eastern	Eastern equine encephali-tis virus (EEEV)
								A. venezuelan	Venezuelan equine en-cephalitis virus (VEEV)
								A. rossriver	Ross River virus (RRV)
								A. semliki	Semliki Forest virus (SFV)
								A. onyong	O'nyong-nyong virus (ONNV)
Riboviria	Orthornavirae	Kitrinoviricota	Flasuviricetes	Amarillovirales	Flaviviridae		Hepacivirus	H. hominis	Hepatitis C virus (HCV)	Hepatitis C: global distribution. Approximately 3% of the world's population is infected (6.6 cases per 100,000 population in Europe). In the Russian Federation, an estimated 2 million individuals are infected. The infection frequently becomes chronic, leading to liver cirrhosis in 20–25% of cases and hepatocellular carcinoma in 3–5% of patients
							Orthoflavivirus	O. encephalitidis	Tick-borne encephalitis virus (TBEV)	Epidemics, epidemic outbreaks, and sporadic cases characterized by febrile illnesses (including yellow fever, dengue, acute hemorrhagic fevers, Zika virus infection, West Nile fever, etc.), as well as encephalitides (tick-borne encephalitis, St. Louis encephalitis, Rocio encephalitis, Murray Valley encephalitis, Japanese encephalitis, Powassan virus infection). Incidence may reach millions of cases, with mortality rates ranging from 10% to 70%, often with long-term neurological sequelae
								O. omskense	Omsk hemorrhagic fever virus (OHFV)
								O. powassanense	Powassan virus (POWV)
								O. denguei	Dengue virus (DENV)
								O. flavi	Yellow fever virus (YFV)
								O. nilense	West Nile virus (WNV)
								O. japonicum	Japanese encephalitis virus (JEV)
								O. murrayense	Murray Valley encephali-tis virus (MVEV)
								O. kyasanurense	Kyasanur Forest disease virus (KFDV)
								O. louisense	Saint Louis encephalitis virus (SLEV)
								O. zikaense	Zika virus (ZIKV)
							Pegivirus	P. hominis	Human pegivirus (HPgV)	Chronic liver infection, typically asymptomatic. Cases of co-infection with other viral hepatitis agents have been reported
		Negarnaviricota	Monjiviricetes	Mononegavirales	Bornaviridae		Orthobornavirus	O. bornaense	Borna disease virus 1 (BoDV-1)	Borna disease: sporadic cases reported in Central Europe, involving the central nervous system (encephalitis), with mortality rates reaching 95–97%
					Filoviridae		Orthoebolavirus	O. sudanense	Sudan ebolavirus	Ebola virus disease: epidemic outbreaks in Africa and Southeast Asia, with imported cases reported in Europe. Mortality ranges from 34% to 90%
								O. zairense	Zaire ebolavirus
								O. restonense	Reston ebolavirus
								O. bundibugyoense	Bundibugyo ebolavirus
							Orthomarburgvirus	O. marburgense	Marburg virus (MARV)	Hemorrhagic fever outbreaks (primarily in Africa, with imported cases in Europe), with mortality around 24%
Riboviria	Orthornavirae	Negarnaviricota	Monjiviricetes	Mononegavirales	Paramyxoviridae	Feraresvirinae	Respirovirus	R. laryngotracheitidis	Human parainfluenza virus 1 (HPIV-1)	Parainfluenza: a seasonal acute respiratory infection with global distribution. In the Russian Federation, it accounts for approximately 17.5% of acute respiratory infections during the epidemic season and about 2.1% among the general population tested. The infection primarily affects the upper respiratory tract, causing rhinitis, pharyngitis, and laryngitis
								R. pneumoniae	Human parainfluenza virus 3 (HPIV-3)
						Orthoparamyxovirinae	Henipavirus	H. nipahense	Nipah virus (NiV)	Paramyxovirus-associated encephalitis (e.g., Nipah virus infection): epidemic outbreaks in Southeast Asia involving pigs and bats as reservoirs. Mortality rates range from 75% to 90%
								H. hendraense	Hendra virus (HeV)	Paramyxovirus-associated encephalitis involving horses and bats (e.g., Hendra virus infection, Australia), with mortality rates of approximately 50%
							Morbillivirus	M. hominis	Measles virus (MeV)	Measles: an acute viral infection primarily affecting children, with global distribution. Clinical features include fever and rash, with complications such as pneumonia, otitis media, sinusitis, and, in approximately 1 per 1,000 cases, encephalitis resulting in severe disability or death
						Rubulavirinae	Orthorubulavirus	O. hominis	Human parainfluenza virus 4 (HPIV-4)	Parainfluenza: seasonal acute respiratory infection with global distribution. In the Russian Federation, it accounts for approximately 17.5% of all acute respiratory infections during the epidemic season and about 2.1% of tested individuals in the general population. The infection predominantly involves the upper respiratory tract, presenting as rhinitis, pharyngitis, and laryngitis
								O. laryngotracheitidis	Human parainfluenza virus 2 (HPIV-2)
								O. parotitidis	Mumps virus (MuV)	Mumps (epidemic parotitis): primarily affects children aged 5–15 years, with worldwide distribution. The disease may occur as sporadic cases or outbreaks throughout the year. Clinical manifestations include sialadenitis, orchitis (in 10–30% of cases), and, in some instances, meningoencephalitis, which may result in permanent hearing loss
					Pneumoviridae		Metapneumovirus	M. hominis	Human metapneumovirus (HMPV)	Seasonal acute respiratory infection with global distribution. In the Russian Federation, accounts for approximately 2.5% of all acute respiratory infections and 0.3% of tested individuals in the general population
Riboviria	Orthornavirae	Negarnaviricota	Monjiviricetes	Mononegavirales			Orthopneumovirus	O. hominis	Respiratory syncytial virus (RSV)	Respiratory syncytial virus (RSV) infection: a seasonal acute respirato-ry infection with global distribution. It primarily affects the lower respiratory tract, causing bronchitis and broncho-pneumonia. High-risk groups include young children, particularly infants in the first year of life (mortality up to 5%). In the Russian Federation, RSV accounts for approximately 2.5% of all acute respiratory infections and 0.3% of tested individuals
					Rhabdoviridae	Alpharhabdovirinae	Lyssavirus	L. rabies	Rabies virus (RABV)	Rabies: sporadic incidence with nearly 100% case fatality once clinical symptoms develop. Global distribution
								L. irkut	Irkut virus (IRKV)	Reported cases of human infection in the Far East of the Russian Federation
							Vesiculovirus	V. indiana	Vesicular stomatitis Indiana virus (VSIV)	Febrile, influenza-like illness characterized by inflammation of the oral mucosa and formation of vesicular lesions. Transmission occurs via arthropod bites or through direct contact with infected animals
								V. chandipura	Chandipura virus (CHPV)	Sporadic cases and epidemic outbreaks in Southeast Asia (e.g., India), presenting with fever, encephalopathy, and encephalitis. Vector: sandflies
								V. piry	Piry virus (PIRYV)	Sporadic cases reported in Brazil, presenting with fever, myalgia, and arthralgia. Vector: sandflies
			Bunyaviricetes	Elliovirales	Hantaviridae		Orthohantavirus	O. hantanense	Hemorrhagic fever with renal syndrome (HFRS) viruses: Puumala virus (PUUV), Hantaan virus (HTNV), Seoul virus (SEOV), Dobrava-Belgrade virus (DOBV), Tula virus (TULV), and other hantaviruses.	Hemorrhagic fever with renal syndrome (HFRS): widespread across Europe, Asia and Africa. In the Russian Federation, 2,700–11,400 cases are reported annually, with more than 95% occurring in the European part of the country, particularly in forested regions. Mortality ranges from approximately 0.4% to 3%
								O. seoulense
								O. puumalaense
								O. dobravaense
								O. andesense	Andes virus (ANDV) and 12 other hantaviruses	Hantavirus cardiopulmonary syndrome (South, Central and North Americas), with a mortality rate of approximately 60%
					Peribunyaviridae		Orthobunyavirus	O. encephalitidis	California encephalitis serogroup viruses, including La Crosse virus (LACV), Khatanga virus (KHATV), Tyaginya virus (TYAV), Inkoo virus (INKV), Jamestown Canyon virus (JCV), and more than 100 other related viruses.	California encephalitis: epidemic outbreaks and sporadic cases in the western United States. In the Russian Federation, viruses of the California serogroup (e.g., Khatanga, Tyaginya, Inkoo viruses) are widely distributed. These infections typically present as febrile illness, occasionally with signs of neuroinfection. Vector: mosquitoes
								O. lacrosseense
								O. khatangaense
								O. tahynaense
								O. jamestownense
								O. bunyamweraense	Bunyamwera serogroup viruses, including Batai virus (BATV), Ngari virus (NRIV), Ilesha virus (ILEV), and other related viruses	Bunyamwera fever, Ilesha fever, and Ngari hemorrhagic fever (Africa). In the Russian Federation, Batai virus is also present. Vector: mosquitoes
								O. bataiense
								O. ileshaense
Riboviria	Orthornavirae	Negarnaviricota	Bunyaviricetes					O. oropoucheense	Oropouche virus (OROV)	Oropouche fever (South and Central America). Vector: biting midges
							Khurdivirus	Kh. volgaense	Khurdun virus (KHURV)	A virus isolated in the Volga delta (Astrakhan region) from the coot (Fulica atra); its pathogenicity for humans remains unknown
				Hareavirales	Arenaviridae		Mammarenavirus	M. lassaense	Lassa virus (LASV)	Lassa fever: epidemic outbreaks in West and Central Africa, affecting 100,000–500,000 individuals annually, with approximately 5,000 deaths. Imported cases have been reported in Europe, the United States, and Japan
								M. lujoense	Lujo virus (LUJV)	Lujo hemorrhagic fever: epidemic outbreaks in Africa with high case fatality rates.
								M. juninense	Junín virus (JUNV)	Argentine hemorrhagic fever: epidemic outbreaks with mortality ranging from 9% to 30%
								M. machupoense	Machupo virus (MACV)	Bolivian hemorrhagic fever: epidemic outbreaks with mortality rates of 15–20%
								M. guanaritoense	Guanarito virus (GTOV)	Venezuelan hemorrhagic fever: epidemic outbreaks, with mortality reaching up to 60% among hospitalized patients; subclinical and mild forms of infection also occur
								M. brazilense	Sabiá virus (SABV)	Arenavirus-associated febrile illness reported in Brazil
								M. chapareense	Chapare virus (CHAPV)	Arenavirus-associated febrile illness reported in Bolivia.
					Nairoviridae		Orthonairovirus	O. haemorrhagiae	Crimean-Congo hemorrhagic fever virus (CCHFV)	Nairovirus infections, including Crimean–Congo hemorrhagic fever (CCHF): Epidemic outbreaks and sporadic cases occur in arid regions of tropical and subtropical zones (Africa, Europe, Asia). The northern boundary of distribution is determined by climatic factors (e.g., cumulative temperature thresholds). Mortality ranges from 16% to 20% in vector-borne transmission (tick Hyalomma marginatum) and may reach up to 50% in cases of contact transmission. n the former USSR countries, additional viruses have been identified, including Issyk-Kul fever virus (Central Asia), Tamdy virus (Uzbekistan, Kyrgyzstan, Turkmenistan, Armenia), and potentially pathogenic viruses such as Artashat (Central Asia) and Sakhalin virus (subarctic coastal regions of European Russia and the Far East)
								O. issykkulense	Issyk-Kul virus (ISKV)
								O. tomdiense	Tamdy virus (TAMV)
								O. artashatense	Artashat virus (ARTV)
								O. sakhalinense	Sakhalin virus (SAKV)
Riboviria	Orthornavirae	Negarnaviricota	Bunyaviricetes	Hareavirales				O. yezoense	Yezo virus (YEZV)	A novel nairovirus associated with ticks Ixodes persulcatus in Siberia, the Russian Far East, Japan, China causing febrile illness
					Phenuiviridae		Phlebovirus	P. siciliaense	Sandfly fever Sicilian virus (SFSV)	Sandfly fevers in southern regions of Europe, Asia, and Africa. Large-scale epidemic outbreaks are caused by more than 70 virus species within this group. Vector: sandflies
								P. toscanaense	Toscana virus (TOSV)
								P. napoliense	Sandfly fever Naples virus (SFNV)
								P. riftense	Rift Valley fever virus (RVFV)	Rift Valley fever: epidemic outbreaks and sporadic cases in Africa and the Arabian Peninsula. Clinical manifestations include febrile illness, hemorrhagic syndrome, and encephalitis. Mortality is approximately 3.5%. Vector: mosquitoes.
							Uukuvirus	U. uukuniemiense	Uukuniemi virus (UUKV)	Antibodies to Uukuniemi virus and Zaliv Terpeniya virus have been detected in humans in Arctic regions. Rukutama virus is considered a potentially pathogenic virus isolated in subarctic coastal areas of the Russian Far East
								U. tyulenyense	Zaliv Terpeniya virus (ZTV)
								U. rukutamaense	Rukutama virus (RUKV)
			Insthoviricetes	Articulavirales	Orthomyxoviridae		Alphainfluenzavirus	A. influenzae	Influenza A virus (IAV)	Influenza: characterized by pandemics and annual epidemics with global distribution. A seasonal acute respiratory infection of zoonotic origin (zoonosis with anthropogenic transmission). Each year, up to 10% of adults and up to 50% of children are affected. High-risk groups include children, adults over 60 years of age, individuals with chronic diseases, and pregnant women. Clinical presentation includes systemic febrile syndrome with catarrhal symptoms such as rhinitis, tracheitis, bronchitis, and pneumonia. During pandemics (e.g., H1N1/pdm09), severe complications may occur, with mortality reaching up to 60% in cases caused by highly pathogenic strains. The overall fatality rate is approximately 0.1%, but it may increase significantly with the emergence of novel pandemic strains
							Betainfluenzavirus	B. influenzae	Influenza B virus (IBV)
							Gammainfluenzavirus	G. influenzae	Influenza C virus (ICV)
							Thogotovirus	Th. dhoriense	Dhori virus (DHOV)	Sporadic cases associated with infection transmitted by ticks of the genus Hyalomma within their geographic range (southern Eurasia and Africa; in the Russian Federation and CIS countries: Astrakhan region, Kyrgyzstan, Azerbaijan, Armenia). The disease often presents encephalitic syndrome and may result in fatal outcomes. Vector: ticks
								Th. bourbonense	Bourbon virus (BRBV)	Reported cases of febrile illness with fatal outcomes in the United States
Riboviria	Orthornavirae	Pisuviricota	Duplopiviricetes	Durnavirales	Picobirnaviridae		Orthopicobirnavirus	O. hominis	Human picobirnavirus	Enteric infections in humans
			Pisoniviricetes	Nidovirales	Coronaviridae	Orthocoronavirinae	Alphacoronavirus	A. chicagoense	Human coronavirus 229E (HCoV-229E)	Seasonal acute respiratory infection with global distribution. In the Russian Federation, accounts for approximately 2.5% of all acute respiratory infections and 0.3% of the total population
								A. amsterdamense	Human coronavirus NL63 (HCoV-NL63)
							Betacoronavirus	B. gravedinis	Human coronavirus OC43 (HCoV-OC43)
								B. hongkongense	Human coronavirus HKU1 (HCoV-HKU1)
								B. pandemicum	Severe acute respiratory syndrome coronavirus (SARS-CoV) and severe acute respiratory syn-drome coronavirus 2 (SARS-CoV-2)	Severe acute respiratory syndrome (SARS-CoV), first identified in China in 2002, with a case fatality rate of 4–11%. Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, emerged in China in 2019 and resulted in a global pandemic. The World Health Organization declared a Public Health Emergency of International Concern. The global fatality rate is approximately 0.9%. In the Russian Federation, approximately 25 million cases were reported between 2020 and 2025, with a mortality rate of 1.8%
								B. cameli	Middle East respiratory syndrome coronavirus (MERS-CoV)	Middle East respiratory syndrome (MERS-CoV), identified in 2012, with a case fatality rate of approximately 34%
				Picornavirales	Caliciviridae		Norovirus	N. norwalkense	Human norovirus	Norovirus gastroenteritis (accounting for 14–17% of all gastroenteritis cases), with global distribution. Occurs as epidemic outbreaks and sporadic cases
							Sapovirus	S. sapporoense	Human sapovirus	Sapovirus gastroenteritis with global distribution
					Picornaviridae	Caphthovirinae	Cardiovirus	C. theileri	Syr Darya fever virus	Syr Darya Valley fever (Kyzylorda region, Kazakhstan; Turkmenistan; foothills of the Sikhote-Alin range in Primorsky Krai). Clinical presentation includes febrile illness and rash, typically with a favorable outcome. Transmission occurs via tick bites. The disease has also been associated with Viliuisk encephalitis, a degenerative neurological syndrome
									Vilyuisk encephalomyelitis virus	Viliuisk encephalitis: a series of epidemic outbreaks recorded in the 1940s–1950s in the Viliuisk River basin (Eastern Siberia)
								C. saffoldi	Saffold virus (SAFV)	Saffold virus-associated gastroenteritis with global distribution, causing severe disease in young children
Riboviria	Orthornavirae	Pisuviricota	Pisoniviricetes			Ensavirinae	Enterovirus	E. alphacoxsackie	Coxsackie A viruses and enteroviruses, including Enterovirus A71 (EV-A71)	Coxsackievirus infections: may be present with meningoencephali-tis, respiratory symptoms, hemorrhagic conjunctivitis, myocarditis, hepatitis, and other manifestations. Also associated with hand, foot, and mouth disease (HFMD). Large outbreaks have been reported in Southeast Asia, particularly among children under 10 years of age. Complications may include meningitis and acute flaccid paralysis, with mortality rates up to 20%. Acute enteroviral uveitis may occur in young children
								E. betacoxsackie	Coxsackie B viruses and echoviruses	Echovirus infections: typically exhibit summer–autumn seasonality and global distribution, with epidemic outbreaks primarily affecting children
								E. coxsackiepol	Poliovirus types 1, 2, and 3; Coxsackie A viruses; non-polio entero-viruses	Poliomyelitis: an acute viral disease predomi-nantly affecting children, involving the central nervous system (primarily the gray matter of the spinal cord). Associated with a mor-tality rate of approxi-mately 10% and residual flaccid paralysis in up to 50% of cases. Had global distribution in the prevaccination era
								E. alpharhino	Rhinovirus A	Rhinovirus infections: account for up to 40–50% of acute respiratory infections, particularly in children. Global distribution
								E. betarhino	Rhinovirus B
								E. cerhino	Rhinovirus C
						Heptrevirinae	Hepatovirus	H. ahepa	Hepatitis A virus (HAV)	Hepatitis A: characterized by epidemic out-breaks and global distribution. Transmission occurs primarily via the fecal–oral route
						Kodimesavirinae	Kobuvirus	K. aichi	Aichi virus (AiV)	Aichi virus-associated gastroenteritis: reported in Southeast Asia, South America, and Europe, primarily affecting children
							Salivirus	S. aklasse	Human klassevirus	Classevirus-associated gastroenteritis in children (Southeast Asia, Australia, Africa, the Americas). Clinical manifestations include diarrhea, fever, vomiting, cough, rhinitis, and rash, typically with a favorable outcome
						Paavivirinae	Parechovirus	P. ahumpari	Human parechovirus (HPeV)	Outbreaks of gastroenteritis, sometimes accompanied by acute respiratory syndrome, neonatal sepsis, and central nervous system involvement. Global distribution
			Stelpaviricetes	Stellavirales	Astroviridae		Mamastrovirus	M. hominis	Human astrovirus (HAstV)	Gastroenteritis outbreaks, particularly among children and immuno-compromised patients. Astroviruses account for approximately 2–9% of acute intestinal infections, but this proportion may reach up to 20%.
Riboviria	Pararnavirae	Artverviricota	Revtraviricetes	Blubervirales	Hepadnaviridae		Orthohepadnavirus	O. hominoidei	Hepatitis B virus (HBV)	Hepatitis B: global distribution. Prior to widespread vaccination, approximately 50 million new cases were reported annually worldwide, with around 2 million deaths: ~ 100,000 due to fulminant hepatitis. ~ 500,000 due to acute infection. ~ 700,000 due to liver cirrhosis. ~ 300,000 due to hepatocellular carcinoma. Transmission occurs primarily via the parenteral route
				Ortervirales	Retroviridae	Orthoretrovirinae	Lentivirus	L. humimdef1	Human immunodeficiency virus 1 (HIV-1)	HIV infection / AIDS: a global pandemic that has been progressively developing since the 1980s. Over time, the infection has evolved from a zoonotic origin into a fully established human-to-human (anthroponotic) transmission. Global distribution, with prevalence reaching 20–25% of the adult population in certain regions of Africa. In the Russian Federation, the number of infected individuals is estimated at 900,000 to 1.25 million
								L. humimdef2	Human immunodeficiency virus 2 (HIV-2)
Ribozyviria					Kolmioviridae		Deltavirus	D. cameroonense, D carense, D. italiense, D. japanense, D. peruense, D. senegalense, D. taiwanense, D togense	Hepatitis D virus genotypes 1–8 (HDV-1 to HDV-8)	Hepatitis D (delta virus infection): Markers of hepatitis D virus infection are detected in 3–21% of HBsAg carriers in different regions of the Russian Federation and in approximately 5% globally. HDV markers are identified in: ~ 70% of patients with fulminant hepatitis B; ~ 60% of patients with chronic hepatitis; ~ 28% of patients with liver cirrhosis
Singelaviria	Helvetiavirae	Dividoviricota	Laserviricetes	Halopanivirales	3 families	Archaeal viruses
Adnaviria	Zilligvirae	Taleaviricota	Tokiviricetes	3 orders	6 families	Archaeal viruses
Pleomoviria	Trapavirae	Calorviricota	Caminiviricetes	Ageovirales	Thalassapleoviridae	Archaeal viruses
		Saleviricota	Huolimaviricetes	Haloruvirales	Nanopleoviridae
Pleomoviria	Trapavirae	Saleviricota	Huolimaviricetes	Haloruvirales	Pleolipoviridae	Archaeal viruses
Efunaviria	Loebvirae	Hofneiviricota	Faserviricetes	Tubulavirales	3 families	Bacteriophages
Volvereviria	Sangervirae	Phixviricota	Microviricetes	7 orders	21 families	Bacteriophages

 

Acute intestinal infections

Acute intestinal infections remain one of the most common infectious diseases worldwide and pose a significant medical and socioeconomic problem. More than 6 billion cases are reported annually³ [13, 14]. Diarrheal diseases remain one of the leading causes of death from infectious diseases. According to global estimates, approximately 1.1–1.5 million people die from diarrheal diseases annually, with a significant proportion of these deaths occurring among children under 5 years of age [15]. The World Health Organization (WHO) reports approximately 1.7 billion cases of diarrheal diseases in children each year, making them one of the leading causes of childhood morbidity [16]. Thus, acute intestinal infections account for a significant proportion of the global burden of infectious diseases and remain a major public health problem, especially in low-income countries with inadequate access to clean water and sanitation⁴ [13]. Among the wide variety of viruses etiologically associated with acute gastroenteritis, five viruses (rotavirus, norovirus, sapovirus, astrovirus, and adenovirus) play a leading role, accounting for 40–56.6% of cases among children hospitalized with diarrhea [13]. Globally in 2021, rotavirus and norovirus were the leading causes of death from diarrhea in all age groups. The prevalence of these viruses varies depending on age groups, the epidemic season, and geographical, environmental, and socioeconomic factors. An analysis of 160 studies from 18 countries between 1980 and 2019 showed that the overall prevalence of rotaviruses, noroviruses, adenoviruses, astroviruses, and sapoviruses was 29.8%, 13.9%, 6.3%, 3.5%, and 3.2% of tested samples, respectively. A number of other viruses capable of replicating in gastrointestinal cells and causing acute intestinal infections are also rare causes of diarrhea or asymptomatic infection: cobuviruses (including the Aichi virus), enteroviruses, adenoviruses (except group F), toroviruses, coronaviruses (including SARS-CoV), parvoviruses (including bocavirus), and others [17]. Most acute intestinal infection pathogens, therefore, belong to RNA-containing viruses of various families, including viruses with a segmented dsRNA genome of the genus Rotavirus (Riboviria: Orthornavirae: Duplornaviricota: Resentoviricetes: Reovirales: Sedoreoviridae), and various representatives of non-enveloped ss (+)RNA families of the order Picornavirales (Riboviria: Orthornavirae: Pisuviricota: Pisoniviricetes): noroviruses and sapoviruses of the family Caliciviridae, and astroviruses of the order Stellavirales (Riboviria: Orthornavirae: Pisuviricota: Stelpaviricetes). Among DNA-containing viruses, of most significance are adenoviruses (Varidnaviria: Bamfordvirae: Preplasmiviricota: Polisuviricotina: Pharingeaviricetes: Rowavirales: Adenoviridae: Mastadenovirus) and small, non-enveloped, single-stranded DNA-containing parvoviruses (Floreoviria: Shotokuvirae: Cossaviricota: Quintoviricetes: Piccovirales: Parvoviridae) (Table). In recent years, using next-generation sequencing (NGS) methods, a number of new RNA viruses of the order Picornavirales and DNA viruses of the family Parvoviridae associated with acute gastroenteritis have been described. Norovirus is the most common cause of acute gastroenteritis in all age groups and causes approximately 700 million cases of gastroenteritis worldwide each year. Rotaviruses remain one of the leading causes of severe diarrhea in children, despite the development and introduction of vaccination in developed countries [18, 19].

In the Russian Federation, according to data from epidemiological studies and reports from Rospotrebnadzor, approximately 700,000–800,000 cases of acute intestinal infections are reported annually. The average incidence rate is approximately 500–600 cases per 100,000 population annually. As is the case worldwide, the majority of etiologically confirmed cases are caused by various strains of rotaviruses and noroviruses⁵.

Influenza and Acute Respiratory Viral Infections

According to the WHO, one in three people worldwide contracts an acute respiratory viral infection (ARVI) and/or the flu each year, with the total number of infected individuals ranging from 1 to 3–5 billion annually. In Russia, 27.3–41.2 million cases are reported each year, 45–60% of which are children. According to the Russian Ministry of Health, in 2004 the economic damage caused by influenza and ARVI amounted to 82.6 billion rubles, accounting for approximately 86% of economic losses from infectious diseases overall [20]. In 2024, this figure, according to the State Report "On the State of Sanitary and Epidemiological Well-being of the Population of the Russian Federation in 2024," reached over 800 billion rubles⁵. The role of influenza infection in exacerbating chronic diseases and causing complications, which are often the cause of death in patients, has been demonstrated. Excess mortality from influenza during epidemics in different age groups ranges from tens to hundreds of thousands of cases, and during a pandemic can reach 1% or more of the total number of cases [21].

All ARVIs are grouped together based on a common airborne transmission mechanism, seasonality, and the development of the primary pathological process in the patient's respiratory tract, which presents with fundamentally similar clinical symptoms. The viruses that cause ARVIs belong to different taxonomic groups and differ in structure and biological characteristics (table). Known human-pathogenic ARVI viruses belong to at least 7 families: RNA-containing viruses of the families Orthomyxoviridae (genera Alphainfluenzavirus, Betainfluenzavirus, Gammainfluenzavirus, Deltainfluenzavirus), Paramyxoviridae (genera Respirovirus, Orthorubulavirus), Coronaviridae (genera Alphacoronavirus and Betacoronavirus), Pneumoviridae (genus Metapneumovirus), Picornaviridae (genus Enterovirus), as well as DNA-containing viruses of the families Adenoviridae (genus Mastadenovirus) and Parvoviridae (genus Bocaparvovirus). Currently, there are more than 200 characterized viruses that cause ARVI; the specific clinical presentation of each is determined by the viruses' tropism for specific segments of the respiratory tract (table). The number of ARVI pathogens is constantly growing. In the first two decades of the 21st century, previously unknown viruses from the families Parvoviridae (HBoV), Picobirnaviridae (genotype 1), and Coronaviridae (SARS-CoV, MERS-CoV, and SARS-CoV-2 viruses) were isolated and identified from patients. The viruses identified contribute to the overall pattern of acute respiratory viral infections (ARVI) but can also cause major epidemics (severe acute respiratory syndrome, Middle East respiratory syndrome) and pandemics (COVID-19) [22, 23].

Replication and reproduction of influenza, parainfluenza, respiratory syncytial virus, rhinoviruses, and seasonal coronaviruses are limited to the respiratory tract, while adenoviruses and enteroviruses replicate in both the respiratory tract and the gastrointestinal tract, often invading the CNS.

Influenza plays a leading role in the etiological structure of ARVI; its annual epidemic causes significant socioeconomic damage to countries at all levels of economic development. In Europe, the United States, and Japan alone, more than 100 million people fall victim to the influenza epidemic. Annually, 20,000–40,000 people die from influenza and its complications in the United States [24]. Economic losses are estimated in the billions of dollars.

Pandemics caused by new variants of influenza viruses or new respiratory infections — resulting from viruses crossing the species barrier from animals — cause particular harm. The 2009 influenza A(H1N1)pdm09 pandemic was caused by a new reassortant of "swine" influenza A virus variants [20]. The influenza A(H1N1)pdm09 virus was initially more virulent than seasonal influenza A strains. The process of influenza A virus reassortment is ongoing, and the M segment of the influenza A(H1N1)pdm09 virus was detected in 2011 in influenza A(H3N2) viruses isolated from infected individuals. Various reassortants of seasonal influenza viruses with swine viruses are periodically detected in humans [25, 26].

Since the beginning of the 21st century, the global epidemic situation has been complicated by cases of human infection with influenza A viruses of zoonotic origin, primarily swine [25, 26] and avian influenza, including subtypes A/H5N1, A/H5N6, A/H3N8, A/H7N4, A/H7N9, A/H9N2, A/H10N3, and A/H10N5. From 2003 to 2025, 964 laboratory-confirmed cases of human infection with the avian influenza A/H5N1 virus were reported, of which 466 (69.3%) were fatal. The highest number of cases was reported in the Western Pacific Region (Australia – 1 case/0 fatalities, Vietnam – 130/65 cases, Indonesia – 200/168 cases, Cambodia – 75/46 cases, China – 57/32 cases, Laos – 3/2 cases). Worldwide, cases have been reported in 25 countries⁶. In recent years, the avian influenza A(H5N1) virus has significantly expanded its range of circulation: whereas it previously caused outbreaks mainly among domestic poultry in Asia and Africa, since 2021 the 2.3.4.4b variant has spread virtually worldwide — to Europe (including Russia), North and South America, the Middle East, and Antarctica — among wild birds and mammals. A particularly significant outbreak occurred among livestock and poultry on poultry farms in the United States in 2024–2025, marking the first time H5N1 was shown to be circulating persistently among cattle and resulting in multiple infections among farm workers. According to the CDC, from March 2024 to May 2025, 70 human cases were confirmed in the United States, including several severe cases and at least one fatality, but no human-to-human transmission was detected [27, 28]. In the Russian Federation, outbreaks of infection among wild and domestic birds caused by the A/H5N1, A/H5N5, A/H5N8 have been detected in recent years in North Ossetia–Alania, Krasnodar Krai, and the Khabarovsk, Astrakhan, Tyumen, Sakhalin, Kaluga, Ivanovo, Oryol, Kursk, Magadan, Belgorod, Chelyabinsk, and Samara regions. In 2020, during an outbreak of influenza A/H5N8 at a poultry farm, 7 employees became infected. In 2022, 54 outbreaks of avian influenza were detected: 5 among wild birds, 42 among domestic birds, and 7 at poultry farms. The current situation increases the risk of new variants of the influenza A virus emerging, which will inevitably lead to the development of new pandemics with unpredictable consequences [20].

Influenza and other ARVIs are most severe in children under one year of age, the elderly, immunocompromised patients, and frequently ill children. According to WHO data, 60% of fatalities are associated with virus-associated diseases: viral or secondary bacterial pneumonia, central nervous system involvement, and the development of sepsis.

In the Russian Federation, surveillance of ARVI is carried out through a network of reference centers overseen by the Influenza Institute in St. Petersburg and the Center for Influenza Ecology and Epidemiology at the D.I. Ivanovsky Institute of Virology of the N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Russian Ministry of Health.

At the beginning of this century, outbreaks of respiratory diseases emerged that were initially zoonotic in nature and caused by a number of coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2) (Riboviria: Orthornavirae: Pisuviricota: Pisoniviricetes: Nidovirales: Cornidovirineae: Coronaviridae), of which the most significant consequences were associated with the COVID-19 pandemic [22]. Pathogens transmitted via the respiratory route exhibited high virulence during the initial phase of entry into the human population (the "stranger encounter" phenomenon). Subsequently, while maintaining and even increasing their high contagiousness, the viruses reduced their virulence, becoming part of the complex of seasonal ARVIs. This is a common outcome of the interaction between the pathogen's and host's population gene pools (evolution) [7]. In the past, other SARS-like viruses likely underwent a similar evolution. The COVID-19 pandemic became the largest global epidemiological event of the 21st century and was characterized by rapid intercontinental spread of the infection, high variability in epidemic waves, and a significant impact on overall mortality rates. According to WHO data, as of January 19, 2026, more than 781,199,368 cases of COVID-19 had been reported worldwide, of which 7,118,889 were fatal (0.91%)2. However, estimates of excess mortality indicate that the actual number of deaths directly or indirectly related to the pandemic is significantly higher and may exceed 14–20 million cases¹. A significant proportion of excess mortality was attributable not only to the direct effects of the infection, but also to "delayed" or indirect deaths linked to the strain on healthcare systems and limited access to routine medical care. The actual number of infected individuals likely far exceeded the reported figures due to testing limitations and underreporting of cases, which complicated the accurate assessment of mortality and the spread of the infection. The COVID-19 pandemic, arising from ongoing evolutionary processes shaping population gene pools [7] in natural ecosystems, demonstrated the need to establish a genomic surveillance system to monitor circulating strains and to track the viral population and its evolution directly within natural reservoirs (the virosphere) prior to their interspecies transmission and "spillover" into the human population. Starting in early 2020, laboratories around the world began conducting mass sequencing of SARS-CoV-2 viral isolates, and the resulting genomic sequences were promptly deposited in international repositories, including the Russian platform for the aggregation of pathogen genomic data, VGARus (Virus Genomic Aggregation of Russia), which provides centralized collection of genomic sequences to address national epidemiological challenges [29].

Human Immunodeficiency Virus and Parenteral Hepatitis

The HIV pandemic, which has a zoonotic origin and began in the 1980s, continues to spread unabated, and attempts to develop vaccines for the prevention of infection have not yet yielded tangible positive results, despite enormous financial investments and the involvement of a large number of first-rate scientific teams engaged in the development. The burden of HIV infection and parenteral viral hepatitis (B and C) remains one of the most significant global public health challenges due to high prevalence, chronic disease progression, the development of severe complications, and significant mortality.

Despite significant differences in the nature of the etiological agent, HIV and the hepatitis B virus belong to the same class – Revtraviricetes (Riboviria: Pararnavirae) – which encompasses all viruses encoding reverse transcriptase. According to the current classification, HIV-1 and HIV-2 belong to the species Lentivirus humimdef1 and Lentivirus humimdef2 (Artverviricota: Ortervirales: Retroviridae: Orthoretrovirinae: Lentivirus) and are retroviruses. The hepatitis B virus belongs to the species Orthohepadnavirus hominoidei (Riboviria: Pararnavirae: Artverviricota: Revtraviricetes: Blubervirales: Hepadnaviridae: Orthohepadnavirus).

The hepatitis C virus is a classic enveloped ss(+)RNA virus and belongs to the species Orthohepacivirus hominis, genus Orthohepacivirus, family Hepaciviridae (Riboviria: Orthornavirae: Kitrinoviricota: Flasuviricetes: Amarillovirales).

These infections share similar routes of transmission, including parenteral, sexual, and vertical transmission, which contributes to their widespread prevalence and the development of co-infections that worsen the prognosis of the disease.

According to current epidemiological estimates, there are approximately 39–40 million people living with HIV worldwide, with about 1.3 million new infections reported annually. Despite expanded access to antiretroviral therapy, annual mortality from HIV/AIDS-related diseases is approximately 600,000–650,000 cases. HIV infection leads to chronic immune deficiency, the development of opportunistic infections and cancer, and requires lifelong treatment, placing a significant burden on healthcare systems [30].

Parenteral viral hepatitis B and C are the leading causes of chronic liver disease, cirrhosis, and hepatocellular carcinoma. Approximately 250–300 million people worldwide are infected with chronic hepatitis B, and approximately 50–60 million with chronic hepatitis C. More than 2 million new cases of hepatitis B and C virus infection occur annually, and the annual mortality rate associated with viral hepatitis is approximately 1.3 million cases, primarily due to liver cirrhosis and hepatocellular carcinoma [31, 32].

Coinfection with HIV and viral hepatitis poses a particular problem, as it is associated with faster progression of liver fibrosis, an increased risk of cirrhosis, and higher rates of liver-related mortality. Viral hepatitis remains one of the leading causes of death among HIV-infected patients receiving antiretroviral therapy [33, 34]. According to global burden of disease studies, HIV infection and parenteral viral hepatitis are among the leading causes of mortality from infectious diseases and account for a significant number of cases of disability and years of life lost [35]. The total mortality from these infections exceeds 1.9 million cases per year. This confirms that HIV infection and parenteral viral hepatitis remain a serious global public health problem and require the further development of prevention, screening, and treatment programs.

Viral transmissible hemorrhagic fevers and zoonotic fevers transmitted by contact

Vector-borne fevers (dengue, yellow fever, chikungunya, Zika, etc.), transmitted by mosquitoes of the genus Aedes (primarily A. albopictus and A. aegypti of the subgenus Stegomyia), are rapidly spreading infectious diseases worldwide. The expansion of the vector's range, urbanization, climate change, and globalization have led to a significant increase in the number of cases of these infections in recent decades: from 500,000 reported cases in 2000 to 14 million in 2024⁷. The vast majority of cases are attributed to dengue fever. According to current estimates, there are approximately 450 million cases of dengue virus infection annually, of which about 100 million are accompanied by clinical manifestations of the disease. However, the number of laboratory-confirmed cases is much lower. According to current estimates, the global economic losses associated with vector-borne infections in tropical and equatorial regions amount to tens of billions of U.S. dollars annually, including costs for treatment, hospitalization, and lost productivity. [36–38]. Under certain conditions, these zoonotic infections can take on the character of anthroponoses, being transmitted via mosquitoes from person to person without the involvement of other vertebrates in an urban epidemiological cycle.

The persistence of natural foci of particularly dangerous zoonotic viral hemorrhagic fevers, such as the filovirus fevers Ebola and Marburg, arenavirus fevers, and the paramyxovirus infections Nipah and Hendra, among others, in equatorial, tropical, and subtropical regions remains a serious public health problem. Despite the relatively small number of cases compared to other infections, the economic and social burden of these diseases is extremely high, due to the severity of the clinical course, the lack of specific prevention and treatment methods, and the need for large-scale anti-epidemic measures, sanitary control, patient isolation, quarantine measures, and restrictions on economic activity. Comprehensive assessments of the 2014–2016 Ebola epidemic indicate that the total economic burden of the epidemic exceeded $50 billion including direct medical costs, productivity losses, reduced economic activity, and indirect mortality from other diseases due to the overburdening of the healthcare system [39, 40]. Furthermore, despite the localized scale of outbreaks, there is a need to establish effective systems for public health surveillance, laboratory diagnostics, training of medical personnel, and the development of vaccines and antiviral drugs [41, 42].

A prime example of a zoonosis with limited circulation evolving into an anthroponosis is the mpox (formerly monkeypox) outbreak that occurred in 2022–2023. For a long time, this infection was considered a zoonotic disease endemic to Central and West African countries, with the potential for local sexual transmission. In 2022–2023, the infection transitioned to sustained human-to-human transmission, spread beyond the African continent, and led to a global outbreak — the largest in history [43]. By 2026, 179,616 laboratory-confirmed cases had been reported worldwide in 145 countries, including countries in Europe, Africa, North and South America, Asia, and Australia⁸ [44, 45]. Economic models show that the cost of combating the mpox outbreak in high-income countries amounted to hundreds of millions of U.S. dollars, while the global costs of vaccination, diagnostics, and epidemiological surveillance related to mpox control are estimated at billions of U.S. dollars [46, 47].

Among infections of this type in the Russian Federation, hantavirus infections are the most significant; they are transmitted through inhalation or ingestion of dried secretions from their primary carriers — certain species of rodents. In terms of the number of reported cases, hemorrhagic fever with renal syndrome (HFRS), caused by hantaviruses, ranks first among all zoonotic viral diseases⁵. The spread of HFRS cases across the country is uneven: in the European part of Russia, the average annual rate is 9.7 cases per 100,000 population, while in the Volga region (for example, the Republic of Bashkortostan) it is 44.5 cases per 100,000 population. HFRS is caused by several species of hantaviruses (Hantaviridae: Orthohantaviridae), with the Puumala virus (Orthohantavirus puumalaense) being the most significant in the European part of Russia [48].

Chronic systemic viral infections

Pandemics of diseases are caused by herpes viruses, papillomaviruses, and polyomaviruses, which have very ancient origins and were present at the dawn of Earth's biosphere. They evolved alongside modern humans as they transitioned from primates to hominids, then to hominins, the genus Homo, and finally Homo sapiens, continuing throughout the development of human society. As a result, more than half of humanity is currently infected at some point in their lives and pays a heavy price for it. There are no signs that the situation will improve. Chronic viral infections caused by herpesviruses (in particular, cytomegalovirus infection and Epstein–Barr virus infection), as well as papillomaviruses and polyomaviruses, represent a significant global burden due to their widespread prevalence and ability to persist latently for life.

Herpesvirus prevalence reaches 60–100% in the human population, with over 90% of adults infected with Epstein–Barr virus [49]. Globally, approximately 3.7 billion people are infected with herpes simplex virus type 1 (HSV-1) and more than 500 million with herpes simplex virus type 2 (HSV-2) [50]. Infection caused by human papillomaviruses is detected in the vast majority of the population, and the prevalence of polyomaviruses also approaches 70–90% among adults [51]. Thus, collectively, we are talking about billions of infected individuals.

The clinical significance of these infections is determined by their role in the development of severe systemic diseases. Epstein–Barr virus is associated with lymphoproliferative disorders and autoimmune diseases (including multiple sclerosis) [49], while cytomegalovirus infection is associated with congenital disorders and complications in immunocompromised patients [51]. Oncogenic types of human papillomavirus are an etiological factor in cervical cancer and a number of anogenital and oropharyngeal tumors [52]. JC polyomavirus causes progressive multifocal leukoencephalopathy, while BK polyomavirus causes graft nephropathy [51].

Thus, chronic viral infections are characterized by high prevalence, multisystemic effects, and a significant contribution to oncological, neurological, and immunopathological morbidity, which determines their importance for global public health.

Bacterial Viruses in Human Infectious Diseases

Bacterial viruses – bacteriophages (phages) – cannot infect human cells and infect only bacterial cells, exhibiting relatively narrow spectra of activity even against these hosts [53]. Moreover, so-called virulent (obligately lytic) bacteriophages have been successfully used for over 100 years as antibacterial agents in phage therapy (PT) [54–56], which has proven not only its efficacy but also its high safety. Furthermore, phages are a dominant component of the gut virome and other parts of the human body, normally causing no pathologies. At the same time, there are numerous examples of the direct and indirect involvement of bacterial viruses in the pathogenesis of human and animal diseases. Nevertheless, in certain pathological conditions, interactions of phage particles from the natural microbiome or those introduced exogenously may exacerbate inflammation as a result of direct interactions between phages and immune system cells. In particular, such phenomena have been described in inflammatory bowel disease (IBD) [57]. While transplanting the viral component from a healthy donor may have a positive therapeutic effect in IBD, transplanting the gut virome from patients with ulcerative colitis into mice exacerbated the symptoms of colitis induced by sodium dextran sulfate [58]. However, most examples of bacteriophage involvement in pathogenesis are associated with so-called temperate bacteriophages (not used for PT). Thus, many bacterial toxins, including the toxin of the diphtheria pathogen, cholera, some botulinum toxins, as well as the Shiga-like toxin of enterohemorrhagic Escherichia coli [59, 60], are encoded not by the main genome of the corresponding bacteria, but by prophages integrated into it. These prophages are not defective and, under certain conditions, can be induced and lead to the formation of viable viral progeny. Prophages can encode other virulence factors, and in some cases, the viral particles themselves can act as such factors. For example, the most virulent strains of Pseudomonas aeruginosa often contain the prophage of the filamentous phage Pf4, which participates in the formation of biofilm structures by facilitating the formation of channels within them; furthermore, particles of this phage can form liquid-crystalline aggregates (tactoids) that reinforce the biofilm matrix or form sheath-like structures around individual cells, protecting the bacteria from various immune system factors and antibiotics. Finally, particles of the Pf4 phage interact with macrophages and, through the expression of certain fragments of their genome within the eukaryotic cell, act on receptors to activate an immune response via an antiviral pathway that is largely ineffective against the phage's bacterial host [61]. These and many other examples show that over billions of years of evolution, the relationship between the viral world and their hosts has gone far beyond the parasite-host paradigm, and currently viruses are directly or indirectly involved in virtually all aspects of their hosts' activities, a phenomenon that is particularly evident in the interactions between bacteria and bacteriophages.

Conclusion

The global virus reservoir harbors a vast potential for pathogens which, due to the continuous evolution of their population gene pools under the influence of the environment, pose a threat of unpredictable outbreaks of emerging and re-emerging infections capable of causing extraordinary epidemic situations (panzootics, pandemics). Certain zoonotic viruses, upon interspecies transmission to humans, have become anthroponotic; others have become zoanthroponotic; and still others remain zoonotic, infecting humans through accidental contact: rabies, viral hemorrhagic fevers (hantaviruses, filoviruses, arenaviruses, etc.), and arboviral infections. Under certain conditions, some zoonotic infections can take on the character of anthroponoses, spreading through contact or, for example, in the urban epidemiological form of dengue, chikungunya, yellow fever, and other tropical fevers.

To ensure biosafety, continuous genomic monitoring of viromes in natural and anthropogenic ecosystems using modern metagenomic methods is necessary. It should be remembered that dormant volcanoes will inevitably erupt, and the emergence of new destructive pandemics and panzootics in the foreseeable future is inevitable. One cannot ignore the possibility of man-made epidemic emergencies that threaten biosafety.

One of the tools for controlling future epidemics and pandemics is the integration of advances in classical virology and molecular biology with the latest innovations in information technology. In the Russian Federation, such a synthesis has been achieved at the Federal State Budgetary Institution Central Research Institute of Epidemiology of Rospotrebnadzor through the creation of the VGARus (Virus Genomic Aggregation of Russia) platform for aggregating pathogen genomic data, which ensures the centralized collection of genomic sequences for epidemiological purposes [29]. According to aggregate data, global databases currently contain over 17 million complete SARS-CoV-2 genomes, reflecting the unprecedented scale of international scientific collaboration and the intensity of genomic surveillance. These datasets are utilized by analytical platforms that provide regular data updates and visualize the spread of viral lineages in near real time. As of December 2025, the VGARus database contains sequencing results for over 440,000 strains and isolates of more than 100 pathogens. The project utilizes cloud technologies, neural networks, and machine learning methods. The SOLAR (System of Laboratory Aggregation Results) platform has been developed and implemented to aggregate laboratory test results, thereby providing the information needed to conduct and monitor anti-epidemic measures. A software system for the operational analysis of the epidemic situation in Russia (EpidSmart) has been developed. The use of supercomputer processing power at the Federal State Budgetary Institution Central Research Institute of Epidemiology of Rospotrebnadzor allows for the analysis of over 1.7 million indicators based on specified parameters within a few hours. The created platform, in combination with domestic developments in the fields of biotechnology, genetic engineering, and molecular diagnostics, ensures the country's biosecurity.

Currently, the number of known viruses that cause human disease exceeds 500 (taxonomically belonging to more than 180 species), and this figure continues to grow as new diagnostic methods are introduced. Viruses, which are ubiquitous across all three domains of the biosphere (archaea, bacteria, eukaryotes), have, as a result of co-evolution with their hosts over the past tens of thousands of years, colonized that part of the biosphere commonly referred to as humanity and, in our time, cause serious harm to human health and are often the cause of death. Emerging and re-emerging viral infections pose a particular threat, posing a biosecurity challenge to both the state and global civilization. All of this necessitates the study of fundamental parameters that determine the interaction between viral populations and humans at various levels, including the molecular level – interaction with receptors (species and tissue tropism, routes of infection and viral spread within the body, pathogenesis); replication forms (lytic, latent, reactivation, malignancy, etc.); the involvement and influence of the cell's internal host components on the virus's life cycle; and interactions with the immune system. The results of these studies will enable the identification of new strategic approaches to prevention (vaccines) and treatment (antiviral drugs and their combinations). There is a clear need to monitor the population gene pool of pathogens in nature, as evolutionary changes in this gene pool lead to the emergence of new variants of the pathogen with altered biological properties, a reduction in the effectiveness of vaccination, or the development of resistance to antiviral drugs.

Viruses are obligate intracellular symbionts of cellular organisms. Their primary form of symbiosis with humans – parasitism – has been discussed above. Recall that parasites are organisms that live at the expense of individuals of another species, being biologically and ecologically closely linked to them in their life cycle, and permanently or temporarily using the host as their habitat [62]. A form of symbiosis in the form of mutualism, where both species benefit, has been established, at least for bacteriophages [2, 65, 63, 64]. Virulent and temperate phages, using humans as a habitat for bacteria inhabiting the gastrointestinal tract, exert a multifaceted influence on all aspects of the macroorganism. A form of symbiosis in the form of commensalism, in which one species benefits at the expense of another without harming it, appears to be characteristic of the archaea and their viruses found in the gastrointestinal tract [65, 66]. At the same time, viruses of bacteria and archaea remain one of the main factors in the mortality of the corresponding microorganisms in nature, and under certain ecological conditions can cause the collapse of local populations of hosts susceptible to them. This is the basis of phage-based antibacterial therapy [67].

Thus, the human virome, as part of the global virome (virosphere), encompasses viruses belonging to all currently known viral superkingdoms (realms), which are widespread among all members of the biosphere – the domains of Archaea, Bacteria, and Eukaryota (table) [2, 3, 7].

Experience in combating new and re-emerging viral infections, taking into account the mistakes and successes of the recent past, must be considered and utilized in planning a system of anti-epidemic measures and in minimizing the consequences of future epidemics and pandemics.

¹ World Health Organization. Global excess deaths associated with COVID-19 2026.

² World Health Organization. WHO Coronavirus (COVID-19) Dashboard 2026.

³ World Health Organization. Diarrheal disease fact sheet 2024. Available at: https://www.who.int/news-room/fact-sheets/detail/diarrhoeal-disease (link available as of: 31.03.2026).

⁴ World Bank. Economic impacts of poor sanitation. 2022. Available at: https://www.worldbank.org (link available as of: 31.03.2026).

⁵ On the State of Sanitary and Epidemiological Welfare of the Population in the Russian Federation in 2024: State Report. Moscow: Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing; 2025.

⁶ Global Human Cases with Influenza A(H5N1), 1997-2026. Available at: https://www.cdc.gov/bird-flu/php/surveillance/chart-epi-curve-ah5n1.html (link available at: 29.04.2026).

⁷ World Health Organization. Dengue and severe dengue. Available at: https://www.who.int/health-topics/dengue-and-severe-dengue#tab=tab_2 (link available at: 31.03.2026).

⁸ World Health Organization. Multi-country outbreak of mpox, External Situation Report, 2025–2026. Available at: https://www.who.int/emergencies/situations/mpox-outbreak (link available on: 31.03.2026).

About the authors

Dmitry K. Lvov

D.I. Ivanovsky Institute of Virology of N.F Gamaleya National Research Center on Epidemiology and Microbiology of Ministry of health of Russian Federation; Central Research Institute of Epidemiology of Rospotrebnadzor

Author for correspondence.
Email: dk_lvov@mail.ru
ORCID iD: 0000-0001-8176-6582

Dr. Sci. (Med.), Professor, Member of the Russian Academy of Sciences, Chief Researcher

Russian Federation, 123098, Moscow; 111123, Moscow

Vasily G. Akimkin

Central Research Institute of Epidemiology of Rospotrebnadzor

Email: crie@pcr.ru
ORCID iD: 0000-0001-8139-0247

Dr. Sci. (Med.), Professor, Member of the Russian Academy of Sciences, Director

Russian Federation, 111123, Moscow

Victor V. Maleev

Central Research Institute of Epidemiology of Rospotrebnadzor

Email: maleyev@cmd.su
ORCID iD: 0000-0001-5748-178X

Dr. Sci. (Med.), PhD, Professor, Member of the Russian Academy of Sciences, Advisor to the Director for Research

Russian Federation, 111123, Moscow

Andrey V. Letarov

Winogradsky Institute of Microbiology, Federal Research Centre "Fundamentals of Biotechnology" of the Russian Academy of Sciences

Email: letarov@gmail.com
ORCID iD: 0000-0002-6991-1983

Dr. Sci. (Bio.), Head of the Laboratory of Microbial Viruses

Russian Federation, 117312, Moscow

Sergey V. Alkhovsky

Central Research Institute of Epidemiology of Rospotrebnadzor; Medical and Biological University of Innovation and Continuing Education of the Federal Medical Biophysical Center named after A.I. Burnazyan FMBA of Russia

Email: salkh@ya.ru
ORCID iD: 0000-0001-6913-5841

Dr. Sci. (Bio.), Corresponding Member of the Russian Academy of Sciences, Advisor to the Director on Scientific Research in the Field of Naturally Occurring and Emerging Infections

Russian Federation, 111123, Moscow; 123098, Moscow

References

Supplementary files