Vol 61, No 3 (2016)

Cover Page

Full Issue


Natural reservoirs of viruses of the genus Hepacivirus, Flaviviridae

Deriabin P.G.


HCV is a cause of acute and chronic liver diseases, including chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Under natural conditions, HCV is able to infect only humans, and only chimpanzees are sensitive to experimental infection. In recent years, viruses genetically related to HCV were discovered in wild mammals (rodents, bats, rabbits), as well as in domestic animals living in close contact with humans (dogs, horses, cows). The hepacivirus genus of the family Flaviviridae, previously represented only by HCV and, presumably, by GBV-B, now includes new related viruses of animals. The results of the study of molecular-genetic and biological properties of the hepaciviruses provide an opportunity to understand the history, evolution, and the origin of HCV. It also opens up the prospect of using HCV homologues of non-primates as a laboratory model for preclinical medical and prophylactic drugs against hepatitis c. It was found that the hepacivirus of horses is the most closely related to HCV among currently known HCV homologues.
Problems of Virology. 2016;61(3):101-106
pages 101-106 views

Mouse embryonic stem cells – a new cellular system for studying the equine infectious anemia virus in vitro and in vivo

Savchenkova I.P., Alekseyenkova S.V., Yurov K.P.


The complexity of the pathogenesis and insufficient knowledge about the slow retroviral infections, which include equine infectious anemia, necessitates finding an adequate laboratory model for the study of the infection process and immunogenesis to create means of prevention and treatment of diseases. Data about strains and cellular tropism of the virus are discussed. It was shown that mouse embryonic stem cells (ESCS) exhibited unique properties and characteristics. In contrast to fibroblasts and other cell types, these cells can be considered as a new cell system for studying EIAV in vitro and in vivo. Under differentiation-inducing conditions they are able to reproduce in vitro embryogenesis cells and form cells of three germ layers. Differentiation of mouse ESCs in the direction of hematopoiesis could contribute new knowledge and understanding of viral tropism EIAV in vitro. ESC can be returned back to the early pre-implantation embryo. Once in the germ cell environment, they participate in the formation of tissues and organs of the developing fetus. Thus, the adaptation of the mouse ESC to the equine EIAV through genetic transformation makes it possible to get closer to the creation of a laboratory model for the study of the in vivo immune response in the lentiviral infection.
Problems of Virology. 2016;61(3):107-111
pages 107-111 views


Comparative analysis of genetic variants of the HIV-1 circulating in the Irkutsk region in 1999 and 2012

Lebedev A.V., Neshumaev D.A., Kazennova E.V., Lapovok I.A., Laga V.Y., Tumanov A.S., Glushchenko N.V., Plotnikova Y.K., Ponomareva O.A., Yarygina E.I., Bobkova M.R.


The pol and env genome regions of the HIV-1 genetic variants circulating in the irkutsk region of russia in 1999 and 2012 were compared. The results of this work showed the dominance of the HIV-1 subtype a IDU-A genetic variant (100%) in this region. No primary resistance mutations in the pol gene in the treatment-naive patients were found. The heterogeneity of the viral population was found to be significantly increased based on the pol and env analysis among HIV-variants isolated in 2012 (12.88% and 2.16%) from the intravenous drug users as compared to HIV-variants that caused the outbreak of the HIV infection in 1999 (1.64% and 0.47%). In addition, the comparison of genetic distances of the pol and env gene sequences in the viruses isolated in 2012 from the HIV-positive persons infected through heterosexual intercourse and intravenous drug use demonstrated that the transmission route influenced the variability of the virus population. Among the viruses of IDU-A variant circulating in the area in 2012 the prevalence of X4-tropic variants was 24.7%.
Problems of Virology. 2016;61(3):112-118
pages 112-118 views

Interaction of herpesviruses with mature human spermatozoa in the model system in vitro

Malolina E.A., Lebedeva A.L., Kulibin A.Y., Evdokimov V.V., Kurilo L.F., Sorokina T.M., Tulenev J.A., Naumenko V.A., Kushch A.A.


The DNA of human herpesviruses (HHV), including the herpes simplex virus (HSV) and cytomegalovirus (CMV), is often identified in ejaculates of patients with urogenital diseases and infertility. At least a part of viral DNA is associated with cell fraction of ejaculate. However, it remains unclear how the semen is infected by the virus. It can be located in gametes or be capable of infecting mature germ cells, including motile sperm cells. In order to resolve this issue, interactions of the CMV and HSV with human sperm cells were studied using an original optimized model of the herpesviral infection of male gametes in vitro. The analysis of the immunofluorescent staining of gametes for viral antigens has shown that CMV infected 2% gametes, while HSV infected 17.26 ± 2.58% gametes. The fraction of progressively motile sperm cells contained 13.99 ± 4.64% infected cells. Localization of HSV was studied by the confocal microscopy. Sometimes, viral gB protein was found on sperm cell membrane. In addition, optical scanning of other cells has shown the intracellular localization of the viral proteins. In the majority of spermatozoa, the viral proteins were observed in the head and neck. In some cells, they were located in the middle piece or, rarely, in the equatorial segment. In general, after in vitro infection HSV antigens were located in the same areas of the sperm cells as in ejaculates from infected patients. According to DNA–DNA hybridization in situ, gametes containing HSV DNA accounted for 16.94 ± 5.28%, which is consistent with the results obtained in the immunofluorescence assay. It can be concluded that mature male gametes are infected by HHV in the genital tract, where the virus binds to the sperm cell membrane and enters the cell. Interaction of HHV with progressively motile sperm cells implies a vertical viral transmission upon fertilization and points to the necessity of testing ejaculate for herpesviruses infections.
Problems of Virology. 2016;61(3):119-125
pages 119-125 views

The effect of combination of glycyrrhizic acid with alpha-glutamyl-tryptophan on the experimental adenoviral infection

Smirnov V.S., Slita A.V., Garshinina A.V., Belyaevskaya S.V., Anikin A.V., Zarubaev V.V.


In this work, the activity of glycyrrhizic acid (GL) and dipeptide alpha-glutamyl-tryptophane (EW) as single preparations or in combination (GL+EW) against experimental adenoviral infection in the syrian hamsters was studied. Application of gl and GL+EW was shown to decrease the level of the adenovirus replication in liver tissue by 0.6 – 1.2 lgTCID50 depending on the composition and time point of the post infection. It was also demonstrated that normalization of the structure of the liver tissue was required, which was shown on the level of both optical and electron microscopy. The results obtained in this work suggest that gl and GL+EW may be considered as potential component of the complex therapy of adenoviral infection.
Problems of Virology. 2016;61(3):125-131
pages 125-131 views

Viral infections and retinoblastoma in children

Saakyan S.V., Myakoshina E.V., Krichevskaya G.I., Slepova O.S., Panteleeva O.G., Andryushin A.E., Khoroshilova-Maslova I.P., Zakharova G.P., Maybogin A.M.


In this work, the results of a comprehensive laboratory examination of 37 children with retinoblastoma were described. The presence of Igm-, IgA, - IgG- antibodies to the herpes simplex virus types 1 and 2, cytomegalovirus (СMV), epstein-Barr virus (eBV), human herpes virus (HHV) type 6, Toxoplasma gondii, mycoplasma hominis and ureaplasma urealyticum in the serum was tested using ELISA. In the polymerase chain reaction the DNA of these pathogens were detected in the blood plasma of 18 patients and tumor biopsy specimens from 10 eyes. The results showed that children with RB were predominantly infected by the herpesviruses, among which prevailed CMV. in 4 of 5 enucleated eyes the DNA of herpesvirus [CMV (2 eyes), EBV (1 eye), HHV 6 (1 eye)] and ureaplasma urealyticum (1 eye) were also present in tumor tissue. Nucleic acid of infectious microorganisms were considerably more often detected in the tumor tissue than in plasma (5 of 10, 1 of 18, respectively; p = 0.023), suggesting thereby the presence of the virus in the eye and its adverse role in the pathogenesis of the RB.
Problems of Virology. 2016;61(3):132-134
pages 132-134 views

Vaccines based on the Far-Eastern and European strains induce the neutralizing antibodies against all known tick-borne encephalitis virus subtypes

Maikova G.B., Chernokhaeva L.L., Vorovitch M.F., Rogova Y.V., Karganova G.G.


Serum of children aged 1 to 16 obtained in the course of clinical trials conducted in the sverdlovsk region in 2011 was used to study the post-vaccination immunity. Children were immunized twice with vaccines against the tick-borne encephalitis (TBE) Tick-E-Vak on the basis of the strain sofjin of the Far-Eastern subtype and FSME-IMMUN Junior based on the neudorfl strain of the european subtype. According to the plaque reduction neutralization test (PRNT), both vaccines have a high immunogenicity: after 30 days since two-time vaccination in the sera of 100% of children immunized with the vaccine Tick-E-Vak and in the 95% of children immunized with the vaccine FSME-IMMUN Junior antibodies (AT) against strain sofjin were identified in protective titers, whereas 24.5% and 21.4% of children, respectively, had antibody titers higher than 1:10000. selected sera of recipients with titers from 1:25 to 1:1000 were examined in the PRNT in a single experiment using the sofjin (Far-Eastern subtype), absettarov (European subtype) and Vasilchenko (Siberian subtype) strains. The two vaccines induced AT against the representatives of all three subtypes.
Problems of Virology. 2016;61(3):135-139
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Antiviral activity of various drugs with different mechanisms of action in patients with experimental tick-borne encephalitis

Krylova N.V., Leonova G.N.


A possible approach to effective, pathogenetically valid treatment of patients with the tick-borne encephalitis (TBE) is a complex therapy with the immunotropic preparations isolated from natural objects. This work is devoted to the comparative study of the antiviral activity of the tinrostim (immunoactive peptide from the optical ganglia of the squid Berritiuthis magister) and some officinal drugs used for prevention and treatment of the TBE (ribavirin, reaferon-EC, cycloferon, 4-jodantipyrin, immunoglobulin human against encephalitis ixodicum) in the experimental models of the TBE. All tested drugs significantly inhibited the proliferation of the highly virulent strain of the TBEV in the sensitive PK cell cultures: ribavirin and immunoglobulin against TBE completely inhibited viral replication (by 100%); cycloferon – by 75%; tinrostim, reaferon-EC, and jodantipyrin – by 50-60%. Therapeutic efficacy of the compounds was evaluated on a model of acute lethal TBE in mice: treatment with cycloferon and immunoglobulin against TBE prevented the mortality in 35-45% of infected animals; tinrostim – in 25%; ribavirin, reaferon-EC, and jodantipyrin – in 5-10%. The combination of the immunoactive peptide, tinrostim, with officinal drugs (ribavirin, cycloferon) was more effective than the treatment with a single drug, thereby indicating the prospects of the use of this therapy for treating TBE.
Problems of Virology. 2016;61(3):139-144
pages 139-144 views

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