Arbovirus and Experimental Production Department

Laboratory of Biology and Indication of Arboviruses

Managed by Doctor of Biological Sciences, Professor A.M. Butenko.

The laboratory was founded by Professor S.Ya. Gaidamovich in 1957.Professor A.M. Butenko has been in charge of the laboratory since 1991.The traditional areas of research are development, improvement and practical implementation of methods for specific diagnostics of arbovirus infections; identification and classification of arboviruses; study of their role in human pathology; control over the epidemic situation in relation to arbovirus infections in the country. On the territory of the USSR, the laboratory staff discovered the circulation of viruses of West Nile (WN), Batai, Tribech, mosquito fevers, Isfahan. Monoclonal antibodies (mAb) to tick-borne encephalitis, yellow fever, Venezuelan equine encephalomyelitis, Crimean-Congo hemorrhagic fever (CCHF), Inco viruses were obtained and characterized.

The following enzyme-linked immunosorbent assay (ELISA) test systems have been developed, characterized, standardized and have found practical application: a) for the detection of specific IgM and IgG antibodies in human blood serum to Sindbis and Chikungunya viruses (Togaviridae family), West Nile, Japanese encephalitis, yellow fever, dengue, Usutu, tick-borne encephalitis (Flaviviridae family), CCHF, Tyaginya, Inko, Batai, Neapolitan and Sicilian mosquito fevers, Ukuniemi, Bhanja (Bunyaviridae family) and Dhori (Orthomyxoviridae family); b) for serological identification of strains and detection of antigens of the listed endemic and relevant for the Russian Federation tropical arboviruses in experimental, clinical and field materials; c) for detection of IgG antibodies to viruses of Eastern, Western and Venezuelan equine encephalitis (Togaviridae family) in equine blood serum; d) for detection of IgG antibodies to CCHF and Batai viruses in the blood serum of sheep.

The proprietary ELISA test systems for the detection of specific IgM, IgG antibodies and antigens of the CCHF and West Nile viruses have been successfully tested at the L.A. Tarasevich State Institute of Standardization and Control of Biomedical Preparations, and were recommended for registration in the Russian Federation by the Committee for Medical Immunobiological Preparations (Minutes No. 6 dated 26.06.2003). For ELISA test systems for the specific diagnosis of WN fever (WNF) (EIA-IgM, EIA-IgG and EIA-antigen WN), a Registration Certificate (FSR 2012/13840) was obtained in 2012, according to which they are approved for use on the territory of the Russian Federation and introduced into the commercial production by ZAO Bioservice. Test systems for the diagnosis of CCHF and tick-borne encephalitis are at the stage of official registration and certification.

The use of proprietary ELISA test systems allowed in 1999 for the first time to establish the significance of the WN virus in the etiology of the WNF epidemic in the southern region of Russia (Astrakhan, Volgograd Regions and Krasnodar Territory), in 2010 - to decipher the WNF outbreak in the Voronezh Region, to verify the first cases of WNF in the Tula Region (2012), the CCHF in the Volgograd Region (2000), Kalmykia (2000), and Dagestan (2001), which was an evidence of a significant expansion of the range of these serious diseases.

The results of studying the immunostructure of the population of the European part of the Russian Federation to the WN virus obtained in the laboratory in recent years confirm this status. It was found that the expansion of the range of foci of CCHF in the northern direction from the known endemic territories in the Russian Federation is associated with climate warming and the formation of new populations of Hyalomma marginatum ticks.

Molecular genetic analysis of strains of CCHF and WNF viruses obtained from sick people in the laboratory indicates the genetic stability of the main variants of these pathogens circulating in the southern regions of Russia over the past decades. The indices of humoral immunity in patients with CCHF and WNF were studied, on the basis of which the criteria and tactics of specific diagnostics of these diseases were determined. New data have been obtained on the role in human pathology and the epidemiological significance of other poorly studied endemic arbovirus infections: Sindbis, Tyaginya, Inko, Batai, Neapolitan and Sicilian mosquito fevers, Ukuniemi and Bhanja. For the first time, the belonging of the Bhanja, Kismayo and Forekarya viruses (from the Bhanja antigenic complex) to the genus Phlebovirus of the Bunyaviridae family was established. A phylogenetic analysis of a group of original and collection strains of mosquito fever, Batai and Rift Valley fever viruses was carried out, ELISA and RT-PCR test systems were created for diagnosing these infections, as well as a group-specific PCR system for the detection of Bhanja virus and other phleboviruses.

Over the past six years, in cooperation with specialists from the Clinical Hospital of Infectious Diseases No. 1 in Moscow, 178 cases of imported tropical arbovirus diseases have been laboratory-verified: dengue fever (157), Chikungunya fever (10), WNF (6), mosquito fevers (3), Rift Valley fever (1); and Japanese encephalitis (1) among those hospitalized after returning from tropical travel. Dengue fever cases were also diagnosed among residents of Tyumen, St. Petersburg, and Khabarovsk. The need for a parallel examination of the blood serum of sick people for IgM antibodies (using the MAC-ELISA method) to dengue, WN, Japanese encephalitis, yellow fever and Chikungunya viruses (taking into account the area of ​​these infections and the territories where the patient was infected) was established for the purpose of differential diagnosis.

For many years, the laboratory has been the WHO Collaborating Center for Arboviruses. On the basis of the laboratory, with the participation of its employees as scientific supervisors and consultants, four doctoral and 61 candidate theses were completed and successfully defended.

Laboratory of Comparative Virology

Managed by Doctor of Medical Sciences, professor I.F. Barinsky.

The laboratory of comparative virology of the Federal State Budgetary Institution N.F. Gamaleya National Research Center of the Ministry of Health of Russia is one of the few working within the Institute of Virology since its organization in 1944.The original name of the laboratory (until 1958) was the laboratory of multi-seasonal encephalitis. Then, at the suggestion of the corresponding member of the USSR Academy of Medical Sciences A.K. Shubladze, who used to manage the laboratory from 1946 to 1975, the laboratory was renamed the laboratory of comparative virology. Since 1975, the laboratory has been headed by Professor I.F. Barinsky. In the laboratory, research was carried out, priority not only for domestic science, but also for world virology: the strains of the tick-borne encephalitis virus were isolated and the etiology of the tick-borne encephalitis epidemic in Russia was deciphered, the strains of the Japanese encephalitis virus were isolated.

The laboratory conducts research on lyssavirus infections (acute encephalomyelitis and multiple sclerosis, street rabies). For the first time in the country, monoclonal antibodies to structural proteins of viruses of the rabies group were obtained, and on their basis a new generation is being developed for the diagnosis and identification of lyssaviruses.

The laboratory for the first time isolated a strain of the mumps virus and developed a killed mumps vaccine. The scientific and practical part of the laboratory staff work determined a special interest in the creation of preventive and therapeutic vaccines for other neuroviral infections: inactivated vaccine against tick-borne encephalitis, vaccine against acute human encephalomyelitis, vaccine against eastern and western equine encephalomyelitis.

The laboratory is a WHO Collaborating Center for the Study of Herpes Virus Infections and a Scientific and Methodological Center of the Russian Ministry of Health for the experimental development of diagnostic and therapeutic antiherpetic drugs and their introduction into public health practice. It also developed a vaccine against HSV-1 and 2, which is the only active drug for the prevention of recurrence of the disease; killed cytomegalovirus vaccine; new efficient immunostimulants are being tested to activate the body's immune responses in chronic viral infections.

During almost 60 years of history, the laboratory staff has published more than ten monographs and over 500 scientific papers in the leading virological and immunological journals in Russia and the world, prepared 30 doctors and 58 candidates of science.

Immunology Laboratory

Managed by PhD in Biological Sciences I.Е. Isaeva.

From 1954 to 1989, the laboratory was headed by Academician of the USSR Academy of Medical Sciences P.N. Kosyakov, director of the Institute of Virology in 1954-1961.P. N. Kosyakov was an outstanding scientist - immunologist and virologist. On the basis of the laboratory, 30 candidates and seven doctors of sciences were trained. Based on the materials of scientific research, five monographs and a large number of scientific papers on immunity have been published.

In 1989, Professor S.O. Vyazov became the head of the laboratory. Under his leadership, studies of the hepatitis C virus were carried out.In 2006, the laboratory was headed by Academician of the Russian Academy of Medical Sciences V.I. Zlobin, who launched research on the tick-borne encephalitis virus. From 2009 to 2016, the laboratory has been headed by Dr. S.V. Gribencha. With his arrival, an experimental model, the rabies virus, was introduced into the laboratory.

Throughout its history, the laboratory has dealt with fundamental issues of general biological laws of antiviral immunity. Advances have been made in the study of the antigenic determinants of the influenza virus, which is of great importance for understanding the evolution of viruses, diagnosis and prevention of influenza. P.N. Kosyakov and his collaborators made a priority discovery - the presence of three antigenic determinants in the hemagglutinin of influenza viruses was proved, which was later confirmed by foreign authors using X-ray structural analysis. A series of works was devoted to the role of specific antibodies and nonspecific inhibitors, which made a great contribution to the study of antiviral immunity. Priority results were obtained regarding the presence of antigenic components of the host cell in the preparations of influenza and parainfluenza viruses, leading to a change in antigenic specificity. The importance of host antigens for the infectious process and the development of protective immunity has been shown. For many years, work has been carried out on the study of the antigenic structure, mapping of the immunodominant hemagglutinin sites of human influenza A and B viruses.

Under the leadership of Professor S.O. Vyazov, in-depth studies were carried out to study the variability of the genome and the mechanisms of development of infection caused by the hepatitis C virus.For the first time in Russia, data on the spread and pathogenesis of new respiratory viruses, metapneumovirus and bocavirus, were obtained.

Since 2006, an important area of ​​work has been molecular genetic studies of tick-borne encephalitis viruses from endemic regions of the Far North and analysis of the correspondence of newly identified isolates to modern vaccine strains.

The discovery by Dr. S.V. Gribenchа of the phenomenon of heterogeneity in the population of street rabies virus strains, which can contain up to three biological clinical variants, was confirmed five years later by the outstanding French scientists Anne Flamand and colleagues. Unique monoclonal antibodies to the G-protein of the rabies virus have been obtained, which, according to our American colleagues from the CDC (Atlanta, USA), have the highest protective activity among the monoclonal antibodies studied.

Currently, the main areas of research are as follows:

• Molecular identification and determination of viral loads for viruses that cause acute respiratory viral infections (influenza, coronaviruses, respiratory syncytial virus, metapneumovirus, bocavirus, rhinovirus, adenovirus, parainfluenza)
• Study of new flaviviruses carried by ticks and mosquitoes, tick-borne encephalitis viruses, West Nile fever, Dengue in invertebrates and vertebrate reservoir hosts, patients' blood, in environmental objects
• Study of antiviral properties and toxicity of artificial RNAs based on complexes of antigen, peptidomimetics and diazabicyclooctane, new immunomodulatory and antiviral drugs (Ingavirin) in vitro and in vivo against influenza viruses, ARVI and tick-borne encephalitis
• Investigation of new isolates of rabies viruses and causative agents of other lyssavirus infections
• Development of therapeutic and prophylactic immunoglobulin for humans based on humanized mouse monoclonal antibodies to the G protein of the rabies virus
• Development of approaches to the creation of the most effective recombinant vaccine based on an adenoviral vector expressing the G-glycoprotein of the rabies virus for the prevention of rabies in humans.