Voprosy Virusologii

1502-005
USAGE OF INTERFERON INDUCERS DURING VIRAL INFECTIONS
Ershov Feliks I., Narovlyansky A.N.

Federal State Budgetary Institution «Federal Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya» of the Ministry of Health of the Russian Federation, 123098, Moscow, Russia
Abstract: Domestic researchers succeeded to create a group of original interferon inducers (II) with a high chemotherapeutic index and suitable for the prevention and treatment of viral infections and a number of other diseases. Clinical application of ii concerns, first of all, a wide range of viral infections: influenza and other acute respiratory viral infections, herpes, hepatitis, encephalitis, rabies, slow and mixed infections, etc. The accumulated experience is generalized and the conclusion is made about the main advantages of II, which induce a balanced synthesis of endogenous interferon without antigenicity of its own. It is emphasized that a single injection of II “includes” synthesis of IFN in certain populations of cells and organs and provides a relatively long circulation of IFN at a therapeutic level and creation of long-term anti-virus resistance. It is concluded that, in general, interferon inducers with pronounced antiviral and immunomodulatory properties are currently used as effective tools for the prevention and treatment of a variety of diseases. The fact that ii different in their chemical nature act at different stages of reproduction of viruses and affect various links of the innate and adaptive immunity explains the increased scope of the application of this group of drugs in medical practice.
Keywords: интерфероны, индукторы интерферона, интерферонотерапия, профилактика и лечение вирусных инфекций, interferons, interferon inducers, interferon therapy, preventive measures and therapy of viral infections

1502-011
EPSTEIN-BARR VIRUS (EBV) IN RUSSIA: INFECTION OF THE POPULATION AND ANALYSIS OF THE LMP1 GENE VARIANTS IN PATIENTS WITH EBV-ASSOCIATED PATHOLOGIES AND HEALTHY INDIVIDUALS
Goncharova Elena V., Senyuta N.B., Smirnova K.V., Shcherbak L.N., Gurtsevich V. E.

Federal State Budgetary Sientific Institution «N.N. Blokhin Cancer Research Center», 115478, Moscow, Russia
Abstract: The Epstein-Barr virus, widespread herpesvirus among the population of the planet, is also the etiologic agent for a number of malignancies. One of the oncoproteins encoded by the virus, the latent membrane protein 1 (LMP1), through activation of the complex signaling pathways is involved in the processes of cell immortalization and transformation. The goal of this work was to study the level of the EBV infection in Russian population and LMP1 polymorphism in patients with benign and malignant EBV-associated diseases and healthy virus carriers. Studies have shown that by the age of 5-9 years the percentage of the infected persons and the level of antibody titers reaches almost the maximum values. With the age, virus specific antibody titers are decreased (with a high percentage of infected persons) and increased again in groups of older persons. The analysis of the nucleotide sequences of the gene LMP1 translated in amino acid (aa) sequences unexpectedly revealed the dominance a low divergent variant LMP1 B95.8A not only in healthy individuals but also in patients with all forms of EBV-associated diseases. Highly divergent variants Ch1 and Med +, containing a deletion of 10 aa, and characterized by elevated transforming activity more often were detected in the tumor tissue samples than in the blood samples/mouth washes of the same patients. Detection of highly transforming variant LMP1 Ch1 in blood samples of healthy individuals indicates that this analog of Chinese variant Cao may persist in any population and is not necessarily associated with the occurrence of the EBV-associated disorders.
Keywords: вирус Эпштейна-Барр, вирусспецифические антитела, латентный мембранный белок 1 (LMP1), полиморфизм LMP1, Epstein-Barr virus, virus specific antibodies, latent membrane protein 1 (LMP1), LMP1 polymorphism

1502-018
TWO CASES OF HYDROPHOBIA IN THE REPUBLIC OF TATARSTAN: IN VIVO AND POSTMORTEM LABORATORY DIAGNOSIS
Khismatullina Nailya A., Gulyukin A.M., Gulyukin M.I., Ivanov A.V., Sabirova V.V., Yuzhakov A.G., Alexandrova N.M., Samerkhanov I.I., Aliper T.I.

Federal Centre for Toxicological, Radiation and Biological Safety; Kazan Federal University, 420075, Kazan, Russia; Federal Centre for Toxicological, Radiation and Biological Safety; All-Russian Research Institute of Experimental Veterinary Medicine, 420075, Kazan, Russia; All-Russian Research Institute of Experimental Veterinary Medicine, 109428, Moscow, Russia; Federal Centre for Toxicological, Radiation and Biological Safety, 420075, Kazan, Russia; All-Russian Research Institute of Experimental Veterinary Medicine; Federal State Budgetary Institution “Federal Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya” of the Ministry of Health of the Russian Federation, 123098, Moscow, Russia
Abstract: The results of rabies in vivo and postmortem laboratory detection in two cases registered in the Republic of Tatarstan are reported: a victim bitten by a wolf in 2002 and another one bitten by a stray dog on Goa island, india, in 2013. In the patient bitten by a wolf cornea imprints studies using the method of fluorescent antibodies (MFA) showed rabies-positive result 6 days before the patient’s death. The results were confirmed by postmortem examination of different parts of the brain and salivary glands using the MFA, enzyme-linked immunosorbent assay (ELISA), optical microscopy, and bioassay methods. in the patient bitten by a stray dog the rabies virus specific antigen was detected by eye cornea studies using the MFA method and saliva studies using the ELISA. The rabies virus genome was also isolated from saliva and tear fluid using nested reverse-transcription polymerase chain reaction (RT-PCR) 9 days before the patient’s death. The in vivo studies results were consistent with the postmortem study of different parts of the brain using the MFA, enzyme-linked immunosorbent assay (ELISA), optical microscopy, and bioassay methods. All the infection-positive results of both in vivo and postmortem studies were consistent with the clinical studies, i. e. rabies diagnosis was confirmed. The analysis of the rabies virus gene G fragment nucleotide sequence of 238 nd length showed a slight difference between the studied isolates (2 rabies) and the RABV AY956319 (1.68%), difference by 10.5% from the Vnukovo-32 vaccine strains and by 10.9 % from the SAD B19 rabies strain, respectively (rabies viruses of 1st genotype). It was also significantly different from the lissaviruses of 2, 4, 5, and 6 genotypes (21.0-32.7%). The obtained results indicate phylogenetic closeness of the studied isolates (2 rabies) with the RABV AY956319 rabies virus strain belonging to the 1st genotype.
Keywords: гидрофобия, прижизненная и постмортальная диагностика, метод флюоресцирующих антител, иммуноферментный анализ, полимеразная цепная реакция, секвенирование, филогенетический анализ, hydrophobia, in vivo and postmortem diagnosis, fluorescent antibody method, enzyme-linked immunosorbent assay, polymerase chain reaction, sequencing, phylogenetic analysis

1502-025
EFFECT OF POINT MUTATIONS IN THE POLYMERASE GENES OF THE INFLUENZA A/PR/8/34 (H1N1) VIRUS ON THE IMMUNE RESPONSE IN A MOUSE MODEL
Kuznetsova Svetlana A., Isakova-Sivak I.N., Kuznetsova V.A., Petukhova G.D., Losev I.V., Donina S.A., Rudenko L.G., Naikhin A.N.

Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376, St. Petersburg, Russia
Abstract: The vaccine strains for live attenuated influenza vaccines (LAIVs) have cold-adapted, temperature-sensitive, and attenuated phenotypes, which are guaranteed by the presence of specific mutations from the master donor virus in their internal genes. In this study, we used mutant viruses of the pathogenic A/Puerto Rico/8/34 (H1N1) that contained ts-mutations in PB1 (K265N, V591I), PB2 (V478L), and PA (L28P, V341L) genes along and/or in different combinations to evaluate the impact of these mutations in the immune responses. Sequential addition of tested mutations resulted in the stepwise decrease in virus-specific serum and, to a lesser extent, mucosal antibody levels. We demonstrated strong positive correlation between virus attenuation (virus titer in lung) and antibody titers. The ts-mutations in PB1, PB2, and PA genes are mostly involved in the modulation of the humoral immunity, but also have a moderate effect on the cellular adaptive immune response.
Keywords: живая гриппозная вакцина, гены полимеразного комплекса, иммунный ответ, live attenuated influenza vaccine, polymerase complex genes, immune response

1502-031
PARAMETERS OF THE CD4-CELL COUNT AND VIRAL LOAD IN HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1) INFECTED PATIENTS
Selimova Lyudmila M., Serebrovskaya L.V., Ivanova L.A., Kravchenko A.V., Buravtsova E.V.

Federal State Budgetary Institution “Federal Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya” of the Ministry of Health of the Russian Federation; Central Research Institute of Epidemiology, Federal Supervision Service for the of Consumer Rights Protection and People's Welfare, 123098, Moscow; Central Research Institute of Epidemiology, Federal Supervision Service for the of Consumer Rights Protection and People's Welfare, 105275, Moscow
Abstract: In this work the specific features of parameters of plasma CD4 T-lymphocytes count and level virus RNA in the HIV-infected patients were studied. 22% correlation between reduction of CD4 cell count and an increase in virus RNA level was observed in persons that did not receive antiretroviral treatment during the third HIV- infection phase. During this phase of infection patients exhibited a growth of the median value of virus load in cases of both rise as decline in CD4 cell count during long observation period. In addition, towards the end of the observation period, the percentage of patients with virus load >3.3 lg copies/ml considerably expanded. 43% correlation between CD4 cell count and duration of the HIV-infection was detected during the fourth infection phase in persons that did not receive antiretroviral treatment. Most of the patients in the third and the fourth infection phases had essential CD4 cell count growth during antiretroviral treatment. Best values were observed in patients with the initial value of CD4 >400 cells/pl belonging to the third HIV-infection phase.
Keywords: ВИЧ инфекция, CD4 T-лимфоциты, вирусная нагрузка, антиретровирусная терапия, HIV-infection, CD4 T-lymphocytes, viral load, antiretroviral treatment

1502-035
ANTIVIRAL ACTIVITY OF AQUEOUS EXTRACTS OF THE BIRCH FUNGUS INONOTUS OBLIQUUS ON THE HUMAN IMMUNODEFICIENCY VIRUS
Shibnev V.A., Garaev Timur M., Finogenova M.P., Kalnina L.B., Nosik D.N.

Federal State Budgetary Institution “Federal Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya” of the Ministry of Health of the Russian Federation, 123098, Moscow, Russia
Abstract: Fractions of aqueous and water-alcohol extracts of the birch fungus Inonotus obliquus have antiviral effect against the human immunodeficiency virus type 1 (HIV-1). Antiviral properties of low toxic extracts were manifested in the concentration of 5.0 pg/ml upon simultaneous application with the virus in the lymphoblastoid cells culture MT-4. The extract of the birch fungus can be used for development of new antiviral drugs, inhibitors of HIV-1 replication when used both in the form of individual drugs and as a part of complex therapy.
Keywords: противовирусная активность, ВИЧ-1, культура клеток, Inonotus obliquus, fntiviral activity, HIV-1, cell culture, Inonotus obliquus

1502-038
VIRAL INDICATORS OF THE INCREASED EPIDEMIOLOGICAL HAZARD OF SUBJECTS FROM HIGH RISK GROUPS OF HEPATITIS C VIRUS PARENTERAL INFECTION
Mikhaylov Mikhail I., Mamedov M.K., Dadasheva A.E.

Chumakov Institute of Poliomyelitis and Viral Encephalitides, 142782, Moscow, Russia; National Center of Oncology, Ministry of Healthcare of the Azerbaijan Republic, AZ1012, Baku, Azerbaijan Republic; Republican Center of the Struggle Against AIDS, Ministry of Healthcare of the Azerbaijan Republic, AZ1022, Baku, Azerbaijan Republic
Abstract: The author detected RNA of the hepatitis C virus (HCV) and estimated its concentration in sera of subjects from groups with high risk of parenteral infection (GHRPI) and clinically healthy subjects infected with the hepatitis C virus (HCV). The results show that the share of the acute hepatitis C reconvalescents with antibodies to HCV among people from GHRPi appeared to be smaller than among infected healthy subjects. The average fraction of sera with high virus load from subjects in GHRPI was nearly two times higher than the fraction number of such sera received from infected clinically healthy subjects.
Keywords: вирус гепатита С, группы с высоким риском парентерального инфицирования, hepatitis C virus, groups with high risk ofparenteral infection

1502-041
INFECTIOUS, IMMUNOGENIC, AND PROTECTIVE CHARACTERISTICS OF THE RIFT VALLEY FEVER VIRUS DEPENDING ON THE PASSAGE LEVEL AND STORAGE CONDITIONS
Zakutskiy Nikolay I., Balysheva V.I., Khukhorova I.Ju., Yurkov S.G.

National Research Institute for Veterinary Virology and Microbiology of Russia, Russian Academy of Agricultural Sciences
Abstract: The report discusses the research into the impact of some factors, especially the passage in a suspension of continuous cells BHK-21/13 and storage at different temperatures, upon immunobiological characteristics of the Rift Valley fever (RVF) virus strain 1974-VNIIVViM. The limits for the passage levels and optimal storage conditions providing maximal infectious and immunogenic activity, as well as protection of the attenuated RVF strain 1974-VNIIVViM, were determined. It was found that the RVF virus growth in VHK-21/23 cell suspension in the course of 20 consecutive passages and storage at -50°C for 1 to 2 years did not reduce any infectious, immunogenic or protective characteristics of the virus. It was also shown that the RVF virus strain 1974-VNIIVViM could be stored at the following temperature ranges: 1 month at 4 to 6°C, 4 months at -10 to -12 °C, 6 months at -20 °C, and up to 2 years at -50 °C.
Keywords: лихорадка долины Рифт, вирус, уровень пассажей, температура хранения, инфекционность, иммуногенность, протективность, Rift Valley fever (RVF), virus, passage level, storage temperature, infectivity, immunogenicity, protection

1502-043
CONTINUOUS CELL SUBLINE A C /9K AND ITS APPLICATION TO THE AFRICAN SWINE FEVER VIRUS STUDY
Balysheva Vera I., Prudnikova E.Yu., Galnbek T.V., Balyshev V.M.

National Research Institute for Veterinary Virology and Microbiology of Russia, Russian Academy of Agricultural Sciences, 601120, Pokrov, Russia; All-Russia Scientific Research Institute for Experimental Veterinary Medicine, 109428, Moscow, Russia
Abstract: A new continuous cell subline A C /9K highly sensitive to the african swine fever virus (ASFV) was prepared. All the tested ASFV strains isolated in the Russian Federation in 2008-2013 proliferated in this cell culture exhibiting hemadsorption and accumulated at a titer of up to 6.5 lg HAU /cm . The cell culture A C /9K can be used for ASFV isolation or determination of its infectious activity and serotype identity. The culture versions of the ASFV strain Stavropol 01/08 at passages 24 and 33 in the cell culture A C /9K lost their pathogenicity for pigs.
Keywords: африканская чума свиней, вирус, культура клеток, гемадсорбция, антитела, вирулентность, иммуногенность, african swine fever, virus, cell culture, hemadsorption, antibody, virulence, immunogenicity