Vol 64, No 5 (2019)


We should be prepared to smallpox re-emergence

Shchelkunov S.N., Shchelkunova G.A.


The review contains a brief analysis of the results of investigations conducted during 40 years after smallpox eradication and directed to study genomic organization and evolution of variola virus (VARV) and development of modern diagnostics, vaccines and chemotherapies of smallpox and other zoonotic orthopoxviral infections of humans. Taking into account that smallpox vaccination in several cases had adverse side effects, WHO recommended ceasing this vaccination after 1980 in all countries of the world. The result of this decision is that the mankind lost the collective immunity not only to smallpox, but also to other zoonotic orthopoxvirus infections. The ever more frequently recorded human cases of zoonotic orthopoxvirus infections force to renew consideration of the problem of possible smallpox reemergence resulting from natural evolution of these viruses. Analysis of the available archive data on smallpox epidemics, the history of ancient civilizations, and the newest data on the evolutionary relationship of orthopoxviruses has allowed us to hypothesize that VARV could have repeatedly reemerged via evolutionary changes in a zoonotic ancestor virus and then disappeared because of insufficient population size of isolated ancient civilizations. Only the historically last smallpox pandemic continued for a long time and was contained and stopped in the 20th century thanks to the joint efforts of medics and scientists from many countries under the aegis of WHO. Thus, there is no fundamental prohibition on potential reemergence of smallpox or a similar human disease in future in the course of natural evolution of the currently existing zoonotic orthopoxviruses. Correspondingly, it is of the utmost importance to develop and widely adopt state-of-the-art methods for efficient and rapid species-specific diagnosis of all orthopoxvirus species pathogenic for humans, VARV included. It is also most important to develop new safe methods for prevention and therapy of human orthopoxvirus infections.

Problems of Virology. 2019;64(5):206-214
pages 206-214 views

The role of Epstein-Barr viral infection and hepatitis B and C in liver pathology

Solomay T.V., Semenenko T.A., Ivanova M.Y.


A review of scientific literature data on clinical and epidemiological characterization of viral hepatitis B, C and Epstein-Barr viral infection is presented. Scopus, Web of Science, MedLine, The Cochrane Library, PubMed, CyberLeninka, RSCI databases were used to find the necessary literature. It was shown that Epstein-Barr virus along with hepatitis B and C viruses plays a significant role in the development of virus-mediated autoimmune liver diseases, as well as other organs (intestine, heart, kidneys, thyroid gland, etc.). The similarity of these nosologies is also evident in the nature of the course of the disease: the presence of a primary infection in a manifest or latent form, with possible subsequent chronization of the process and its periodic reactivation. Wide distribution of pathogens in the human population determines the possibility of mixed infections with Epstein-Barr virus and hepatitis B and C viruses, however, this problem has not been adequately described in the scientific literature. The review suggests that the role of Epstein-Barr virus in the development of liver diseases and extrahepatic pathology should not be ignored, and the combination of this pathogen with hepatitis B and C viruses required further in-depth studies.

Problems of Virology. 2019;64(5):215-220
pages 215-220 views


Results of investigation of ticks in Volga river delta (Astrakhan region, 2017) for Crimean-Congo hemorrhagic fever virus (Nairoviridae, Orthonairovirus, CCHFV) and other tick-borne arboviruses

Vakalova E.V., Butenko A.M., Vishnevskaya T.V., Dorofeeva T.E., Gitelman A.K., Kulikova L.N., Lvov D.K., Alkhovsky S.V.


Introduction. There are natural foci of Crimean-Congo hemorrhagic fever (CCHF) that vectored by Hyalomma marginatum ticks in Volga river delta (Astrakhan region, South of Russia). The circulation of Dhori virus (DHOV) (Thogotovirus: Orthomyxoviridae) has been also shown here. We hypothesized that other tick-borne arboviruses are also likely to circulate in the region. In particular, Bhanja virus (Phlebovirus: Phenuiviridae), Wad Medani virus (Orbivirus: Reoviridae), and Tamdy virus (Orthonairovirus: Nairoviridae), which were found to circulate in neighboring regions and are vectored by Haemaphysalis spp., Dermacenter spp., and Hyalomma spp. ticks.

Goals and objectives. The aim of the study was to examine ixodid ticks in Volga river delta for the presence of CCHFV, DHOV, Bhanja virus, Wad Medani virus, and Tamdy virus.

Material and methods. Ticks were collected in Volga river delta in 2017. We used molecular genetic methods for the detection and analysis of nucleic acids (PCR, sequencing, phylogenetic analysis).

Results. We detect CCHFV and DHOV RNA in H. marginatum ticks. The rate of infected H. marginatum ticks was 1.98% for CCHFV and 0.4% for DHOV. The results of genetic analysis showed that found DHOV strains are almost identical (99- 100% in the M gene) and forms a separate genetic lineage alongside of Batken virus from Central Asia. At the same time, Bhanja virus, Wad Medani virus, and Tamdy virus were not found in ticks, collected in this region.

Conclusions. DHOV is circulating in the natural foci of CCHF in the Volga river delta. The ratio of infection of H. marginatum with CCHFV and DHOV was determined for the first time.

Problems of Virology. 2019;64(5):221-228
pages 221-228 views

Diagnostics of nasopharyngeal carcinoma with Epstein-Barr virus (Herpesviridae, Lymphocryptovirus, HHV-4) serological and molecular markers in cases of undetected primary tumor location

Senyuta N.B., Smirnova K.V., Kondratova V.N., Ignatova A.V., Mudunov A.M., Dushenkina T.E., Liechtenstein A.V., Gurtsevich V.E.


Introduction. The reasons of late diagnosis of nasopharyngeal carcinoma (NPC) are the long asymptomatic course of the pathological process, the anatomical structure of the nasopharynx, often small, visually and endoscopically undetectable tumor and other factors. It is proved that the Epstein-Barr virus (EBV) is an etiological agent in the most common undifferentiated non-keratinizing histological type of NPC (uNPC).

The aim of the work was to assess the significance of diagnostic markers of EBV (titers of humoral antibodies to the virus and the concentration of viral DNA in plasma) for the diagnosis of uNPC in a group of patients with metastatic lesions of the cervical lymph nodes without an identified localization of the primary tumor focus.

Material and methods. The material for the study was blood plasma of 83 patients with metastatic lesions of the cervical lymph nodes and not established localization of the primary tumor. Plasma samples were tested for the anti-EBV IgG and IgA antibody content and titers and the concentration of viral DNA.

Results and discussion. The data obtained indicate that the parallel testing of blood plasma for EBV-specific antibodies and viral load is a useful tool for preliminary screening of uNPC patients. The final diagnosis is confirmed by the data of subsequent morphological and instrumental studies. Several examples also show that the concentration of viral DNA in the blood plasma of patients with uNPC reflects the effect of the therapy and the prognosis of the disease: remission, stabilization of the tumor process, relapse or metastasis.

Conclusion. Although the titers of virus-specific antibodies are found to reflect clinical manifestations of the disease less accurately than the plasma concentrations of viral DNA, serological markers are extremely important for the preliminary diagnostics of uNPC in cases of undetected primary tumor location. They are also useful for primary screening of this neoplasm among individuals at risk.

Problems of Virology. 2019;64(5):229-237
pages 229-237 views

Ophthalmic drug films in the therapy of experimental herpetic keratoconjunctivitis

Ivanova A.M., Imomalieva K.M., Narovlyansky A.N., Izmest’eva A.V., Sarymsakov A.A., Bilalov E.N., Ershov F.I.


Introduction. The complexity of the treatment of herpetic keratoconjunctivitis is due to the severity of the disease, complications, the transition to chronic relapsing forms and the insufficient effectiveness of the drugs used, which leads to a steady increase in the number of patients.

The aim of the study was to evaluate the therapeutic efficacy of the eye drug films «GlazAvir» in the experimental model of acute herpetic eye infection in rabbits.

Research objectives: to study the specific activity of «GlazAvir» and compare the long-term indicators of the level of manifestation of individual clinical signs of keratoconjunctivitis.

Material and methods. In the work we used rabbits of the Chinchilla breed, the herpes simplex virus type 1 and the eye drug films «GlazAvir». A model of ophthalmic herpetic infection was formed by infection of rabbits with virus-containing material of a pre-scarified eye cornea against the background of local anesthesia. Аnimals were treated with the drug «GlazAvir» - 1 application per day for 7 days. Animals were observed daily for 15 days, then every 3 days until the 25th day of observation. The effectiveness of the drug was evaluated at the peak of the development of the pathological process.

Results and discussion. There was a decrease in mortality from 50 to 20%, and an increase in average life expectancy by 27.87%, compared with the control in animals treated with «GlazAvir». It was noted after activation of herpetic keratoconjunctivitis on the 2nd – 5th day, at the peak of the disease (6–9th day) a statistically significant decrease in the activity of the pathological process (p<0.05) by rabbits treated with the «GlazAvir» ophthalmic drug films. The tendency to normalization by the rabbits treated with the «GlazAvir» preparation was observed until the 14th day.

Conclusion. The data obtained indicate the pronounced effectiveness of the «GlazAvir» preparation in the treatment of experimental herpesvirus keratoconjunctivitis.

Problems of Virology. 2019;64(5):238-245
pages 238-245 views

Markers of hepatitis A in the monkeys of the Adlers primate center

Dogadov D.I., Korzaya L.I., Kyuregyan K.K., Karlsen A.A., Mikhailov M.I., Lapin B.A.


Hepatitis A is a widespread viral infection. The HAV strains of “human” and “monkey” origin are similar in their morphological and antigenic properties, but differ genotypically.

The aim of this research was a comparative study of serological and molecular-genetic markers of HAV infection in monkeys born at the Adler Primate Center and in those imported from different countries.

Material and methods. Fecal samples (n = 313) and serum (n = 266) from various species of monkey using ELISA and RT-PCR were studied.

Results and discussion. The frequency of anti-HAV-IgG was high (78.9%) in imported animals (vervet monkeys from Tanzania and cynomolgus monkeys from Vietnam) and as well as in various species of monkeys (rhesus monkeys, cynomolgus monkeys, green monkeys and papio hamadryas) of the Center (88.6%). At the same time, in the imported monkeys, the markers of “fresh” HAV infection (IgM-27.2%, Ag-HAV-16.7%, RNA-22.0%) were detected significantly more often (p> 0.05) than in monkeys kept at the Colony (IgM-7.5%, HAV-Ag – 5.2%, RNA – 3.6%). In general, anti-IgG reactivity ranged from 1.064 to 2.073 OD450, anti-IgM ranged from 0.546 to 1.059 OD450. The number of HAV-Ag was 0.496 – 1.995 OD450. RNA HAV only in rhesus monkeys and cynomolgys monkeys born at the Colony, as well as in imported vervet monkeys was detected.

Conclusions. The data obtained indicate a wide circulation of HAV among monkeys born in the Adler Primate Center and among the imported animals. Markers of “fresh” HAV infection varied depending on the species of monkeys and their origin.

Problems of Virology. 2019;64(5):246-249
pages 246-249 views

Phylogenetic analysis and distribution of far eastern tick-borne encephalitis virus subtype (Flaviridae, Flavirus, TBEV-FE) from Asia

Leonova G.N., Belikov S.I.


To date, a lot of data on molecular genetic characteristics of different tick-borne encephalitis virus strains has appeared. Only on the basis of the E protein genome, sequences of about 1,500 TBEV strains were registered in GenBank.

The purpose of the work – revision and comparative analysis of data on complete genomes sequences of the Far Eastern subtype of TBE virus strains distributed in the Asian part of Eurasian continent.

Material and methods. The data on the complete genomes of 84 strains of TBEV isolated in Asia were used; phylogenetic analysis was performed.

Results and discussion: it was shown that variants of the TBEV of the Far Eastern subtype are circulating here and form three separate clusters (Sofjin, Senzhang- и Shkotovo-like strains). Sofjin strain (Sofjin-1953, Sofjin-Chumakov, Sofjin-KSY) was considered to be the reference for Far Eastern TBE virus subtype strains and a cluster of Sofjin-like strains. Sofjin-like strains were not found in China and Japan, but widely distributed throughout the area of Primorsky and Khabarovsk krai. The group of Senzhang-like strains was distributed in China, Eastern Siberia, Khabarovsk krai and northern Primorsky krai, but was not found in Japan (Hokkaido). According to molecular genetic characteristics the youngest and more genetically homogeneous group was the Shkotovo-like strains, isolated in the southern part of Primorsky krai, however not found on Hokkaido Island (Japan).

Conclusion: revision of the complete genome characteristics of TBEV strains revealed the features of micro-evolutionary process of viral populations in the Asian part of Eurasia, show the individual affection of strains to certain territories, as well as detect random finds of such strains in the territories of other natural foci.

Problems of Virology. 2019;64(5):250-256
pages 250-256 views

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