Vol 63, No 2 (2018)



Borisevich S.V., Stovba L.F., Paveliev D.I.


A new taxon of the subfamily Chordopoxvirinae that may represent a new genus of smallpox viruses is considered in this review. The distribution of gray squirrels (Sciurus carolinensis) throughout the UK during the 20th century and the decrease in the population of red squirrels (Sciurus vulgaris) is one of the most well-documented cases of ecological change of local fauna by the introduced species. The tendency to expand the distribution of the smallpox virus from Great Britain to the Western part of Europe has been noted. The genetic peculiarities of the genome of the poxvirus of squirrels, which determine its biological properties, as well as evolutionary relationships with other poxviruses, are separately described. Determination of the size of the genome by restriction analysis, sequencing of the whole genome, determination of the content of G/C nucleotide pairs, and functional mapping of the majority of genes made it possible to construct a phylogenetic tree. Phylogenetic analysis shows that this is a new representative of the subfamily Chordоpoxvirinae located between the viruses of the molluscum contagiosum and parapoxviruses. Serological and molecular biological methods are used to reveal and identify the causative agent of smallpox. The use of electron microscopy is limited in grey squirrels, due to the absence of organ damage and reproduction of the virus. Identification of the DNA of the causative agent of poxvirus of squirrels based on the use of different types of polymerase chain reaction (nested and in real time) overcomes all these limitations.
Problems of Virology. 2018;63(2):53-57
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Sizikova T.E., Lebedev V.N., Karulina N.V., Borisevich S.V.


The data on a recently revealed novel filovirus (Lloviu virus, family Filoviridae, genera Cuevavirus) in Europe are viewed in this issue. The molecular-biological properties of genome fragments of Lloviu virus were isolated from perished bats (Miniopterus sсhreibersii). Because infectious Lloviu virus has not been isolated yet, the capacity of virus to infect cells of different species and its potential to cause disease in humans is unclear. The recombinant vectors (vesicular stomatitis virus and plasmids) expressing structural proteins of Lloviu virus were used to study different elements of the virus. The question of interaction of structural proteins of Lloviu virus expressed by recombinant vectors with receptors of bat and human cells is considered. The possibility of pathogenicity of the novel agent for humans is considered. The conclusion is made about the necessity of continuous epidemical and epizootical monitoring of the new filovirus infection.
Problems of Virology. 2018;63(2):58-61
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Lvov D.K., Burtseva E.I., Kirillova E.S., Kolobukhina L.V., Mukasheva E.A., Trushakova S.V., Feodoritova E.L., Merkulova L.N., Krasnoslobodtsev K.G., Garina E.O., Fedyakina I.T., Aristova V.A., Vartanyan R.V., Kisteneva L.B., Deryabin P.G., Prilipov A.G., Rosatkevich A.G., Breslav N.V., Kruzhkova I.S., Belyaev A.L., Aksel’Rod E.V., Sadykova G.K., Shlyapnikova O.V., Bazarova M.V., Devyatkin A.V.


The article presents the features of the influenza virus circulation for the period from October 2016 to May 2017 in some territories of Russia collaborating with the D.I. Ivanovsky Institute of Virology, Federal State Budgetary Institution “N.F. Gamaleya Federal Research Centre for Epidemiology and Microbiology”, Ministry of Health of the Russian Federation. One of the 2016-2017 season’s peculiarities in Russia and countries of the Northern hemisphere was the earlier start of an increase in ARD morbidity with peak indexes reached towards the end of December 2016 - January 2017. First, influenza A(H3N2) virus was predominant; then, it was followed by influenza B virus activity observed until the end of the season. The indexes of morbidity were higher than in the previous season, while the rates of hospitalization and mortality were lower, lethal cases being detected in persons 65 years old and older. Epidemic strains of influenza A(H3N2) virus belonged to 3c.2a genetic group, reference strain A/Hong Hong/4408/2014, and its subgroup 3c.2a1, reference A/Bolzano/7/2016, that are antigenically similar. Strains of influenza B virus were antigenically similar to the B/Brisbane/60/2008 vaccine virus. Strains were sensitive to oseltamivir and zanamivir. The share participation of non-influenza ARI viruses was similar to preliminary epidemic seasons. WHO has issued recommendations for influenza virus vaccines composition for 2017-2018 for the Northern hemisphere.
Problems of Virology. 2018;63(2):61-68
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Tsybalova L.M., Stepanova L.A., Shuklina M.A., Petrov S.V., Kovaleva A.A., Potapchuk M.V., Shaldzhan A.A., Zabrodskaya Y.A., Egorov V.V.


One of the main problems in the area of influenza prophylaxis and pandemic prevention is the development of cross-reactive vaccines, i.e. vaccines directed against all subtypes of human influenza viruses. Such vaccines are being developed in many countries for more than 10 years. A number of vaccines are presently undergoing clinical trials. We created Uniflu candidate vaccine based on recombinant HBc4M2e protein consisting of 4 tandem-connected copies of the highly conserved ectodomain of M2 protein of the influenza A virus. These 4 copies were genetically fused to the carrier protein, namely hepatitis B core antigen. Commercially available Derinat was used as adjuvant in the candidate vaccine. Preclinical studies on laboratory animals (mice, ferrets) demonstrated that immunization with Uniflu leads to significantly higher level of specific immunoglobulins in the blood and bronchoalveolar lavages. Moreover, it produces immunoglobulins belonging to subtype IgG2a that is the most important mediator of antibody-dependent cytotoxicity. The vaccine under review stimulates the proliferation of T-lymphocytes, as well as the formation of CD4+ and CD8+ T-cells synthesizing ɣ-IFN. When infected with the lethal doses (5 LD50) of influenza A viruses of the subtypes H1N1, H2N2, H3N2, and H1N1pdm09, immunized animals typically developed mild form of illness. This kept them alive in 90-100% of cases, which demonstrated almost complete protection from death. Replication of the virus in the lungs of immunized mice was reduced by 1.8-4.8 log10. High immunogenicity of the vaccine, and reduced clinical symptoms following experimental infection, were demonstrated in ferrets as well. The developed recombinant vaccine Uniflu has high specific activity and cross-protection. Uniflu can be proposed as pre-pandemic vaccine, provided that it passes clinical trials.
Problems of Virology. 2018;63(2):68-76
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Kondratova V.N., Lomaya M.V., Ignatova A.V., Dushenkina T.E., Smirnova K.V., Mudunov A.M., Lichtenstein A.V., Gurtsevitch V.E., Senyuta N.B.


The etiological role of the Epstein-Barr virus (EBV) in the development of an undifferentiated histological variant of nasopharyngeal carcinoma (uNPC) found for the first time in regions with a high incidence of this pathology, the Southern provinces of China and the countries of Southeast Asia, and later in the rest of the world, has served as a basis for the widespread use of EBV serological markers for the diagnosis of this form of tumor. In recent years, the use of a test based on the quantitative determination of the EBV DNA concentration in the blood plasma of uNPC patients for early detection and monitoring of the disease has become widespread in endemic regions. In non-endemic regions, such studies virtually have not been carried out, and moreover, the comparative evaluation of the significance of two viral markers, serological and EBV DNA load in the bloodstream of uNPC patients, for diagnostics and evaluation of the therapeutic effect was not investigated. The aim of this study was to compare the clinical value of two serological markers and plasma EBV DNA load in uNPC patients from non-endemic region (Russia). The obtained results indicate that IgA antibodies to the viral capsid antigen (IgA/VCA) and plasma EBV DNA concentration can be successfully used for the diagnosis of uNPC, while IgG/VCA antibodies have no practical significance as an uNPC marker. In addition, it was found that plasma EBV DNA load is more sensitive marker of uNPC than IgA/VCA titers because DNA copy numbers reflect more accurately the effect of the therapy and the clinical state of patients at the stages of remission or relapse. It was shown for the first time that in the non-endemic region the simultaneous evaluation of IgA/VCA antibody levels and the plasma EBV DNA loads are the most effective markers for the diagnostics of uNPC. However, we believe, that it is more practical to use IgA/VCA antibody levels for uNPC screening, and plasma EBV DNA copies - for monitoring of the disease.
Problems of Virology. 2018;63(2):77-84
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Yaroslavtseva N.G., Tikhomirov D.S., Romanova T.Y., Ignatova E.N., Tupoleva T.A., Filatov F.P., Gaponova T.V.


Introduction. Human herpes virus type 6 (HHV 6) can cause serious infectious complications in immunodeficient patients. It is also capable of integrating into the genome of the infected cell. Due to this, there can be a misdiagnosis between viral integration and active infection during laboratory diagnostics. Thus, determination of HHV 6 infection using proper laboratory tools is relevant. Also the data on viral interference of HHV 6 and other herpes viruses are very poor especially for patients with hematological malignancies. The aim of the study was to identify laboratory markers of HHV 6 and the form of infection in patients with hematological malignancies. Materials and methods. 98 patients with hematological malignancies positive for HHV 6 DNA during the infectious complication were enrolled in the study. Viral load in leukocytes and plasma of peripheral blood, antiviral M and G immunoglobulins and peripheral blood leukocytes count were evaluated. Results. The majority of patients (66 out of 98, 67.3%) showed laboratory signs of latent HHV 6. Integrated HHV 6 was suspected in 2 patients due to high viral load (1.5x105 copies and 1.7x105 copies), but it was not confirmed subsequently. Additional testing of HCMV and EBV in patients with laboratory signs of active HHV 6 infection revealed the superiority of monoinfection over mixed infection (20 of 32, 62.5%). In cases of mixed infection, the most common co-infectant was HCMV observed in 9 out of 12 (75%) cases. Mild leukopenia accompanied HHV 6 active infection. Conclusion. Laboratory signs of latent HHV 6 tend to be prevalent in patients with hematological malignancies. In patients with laboratory markers of active HHV 6, the monoinfection demonstrated the superiority over mixed one. In cases of mixed infection, HCMV appeared to be the most commonly co-infectant. No cases of an integrated form of HHV 6 have been observed. The viral load of HHV 6 in leukocytes and blood plasma is almost 3 times lower in patients with a mixed infection than with a monoinfection. Active replication of HHV 6 was accompanied with mild leukopenia.
Problems of Virology. 2018;63(2):84-90
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Unasova T.N., Binyatova A.S., Phadeykina O.V., Sarkisyan K.A., Movsesyants A.A., Ignatyev G.M., Volkova R.A., Tereshkina N.V., Sidorenko E.S., Ilyasova T.N., Sukhanova L.L.


Until recently Rubella has been a wide spread infection. Thanks to vaccination against rubella, taking part in the global elimination program of “manageable infections” of WHO and adoption of the program “Elimination of measles and rubella in Russian Federation” the morbidity index of rubella has reached the sporadic level. One of the determining conditions of rubella elimination is application of high-quality vaccines that satisfy international standards. In Russian Federation, foreign rubella vaccines certified in our country were used for several years. In 2008, the commercial production of domestic vaccine began. It is widely known that the required quality of immunobiological medications is achieved using adequate production conditions and standard technological process. That is why during the production of domestic rubella vaccine, all the rules and requirements of Russian regulatory authorities and international recommendations are followed. In this article, a retrospective analysis of domestic vaccine against rubella according to laboratory options of quality in 2012-2017 is given. The results of the analysis show that the medication demonstrates stable high quality that is indicative of secure production technologies.
Problems of Virology. 2018;63(2):90-96
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