Influenza Etiology and Epidemiology Laboratory

Managed by Doctor of Medical Sciences E.I. Burtseva.

The research that are currently being carried out in the laboratory were initiated by Honored Scientist of the RSFSR, Professor M.I. Sokolov, Professor A.S. Gorbunova, Academician of the USSR Academy of Medical Sciences V.M. Zhdanov, Honored Scientist of the RSFSR, Professor L.Ya. Zakstelskaya, Honored Scientist of the Russian Federation, Professor A.N. Slepushkin.

In accordance with the order of Rospotrebnadzor No. 373 dated March 31, 2005 "On improving the system of epidemiological surveillance and control of influenza and acute respiratory viral infections", the laboratory was assigned the functions of the Center for Ecology and Epidemiology of Influenza (CEEI). In order to further implement the International Health Regulations (IHR 2005) on the territory of the Russian Federation, by the order of Rospotrebnadzor No. 88 dated March 17, 2008 "On measures to improve monitoring of pathogens of infectious and parasitic diseases", he laboratory was assigned the functions of one of four Reference Centers for influenza monitoring in the Russian Federation.

Laboratory for specific prevention of viral diseases

Managed by Doctor of Biological Sciences, Professor T.I. Aliper.

The laboratory is engaged in the creation of means for the specific prevention of viral anthropozoonoses. The methods of classical virology, molecular biology, epidemiology, immunology are used.

The laboratory has developed and introduced into practice live viral vaccines against diseases caused by coronaviruses, influenza A virus.

The current development is an inactivated vaccine against the highly pathogenic influenza A virus subtype H5N1. The laboratory creates new generation vaccines based on recombinant technologies. DNA vaccines have been developed against diseases caused by pestiviruses.

Approaches to the creation of influenza vaccines based on recombinant viruses obtained by reverse genetics have been developed.

About Tissue Culture Laboratory

On the basis of the Tissue Culture Laboratory of D.I. Ivanivsky Virology Institute, the Collection of Animal and Human Cell Cultures is maintained, which includes more than 150 certified cell lines that are widely used in virology and biotechnology. All certified lines are included in the catalog of the All-Union Collection of Cell Cultures (1991) and the European Catalog of Human and Animal Cell Lines (1993). The laboratory has created a working and seed pools of the vaccine cell line Vero (B), characterized according to the WHO requirements, which can be used for the preparation of viral vaccines and test systems. An antiherpetic vaccine is currently being produced on the basis of this line.

Laboratory of Respiratory Viral Infections with Drug Approbation

Managed by Doctor of Medical Sciences, professor L.V. Kolobukhina.

The laboratory is a subdivision of the department of viral hepatitis and clinical virology created in 1948.The scientific works of Professor F.G. Epstein, Academician of the USSR Academy of Medical Sciences V.M. Zhdanov, Professor E.S. Ketiladze reflect the results of fundamental and applied research in the field of clinical virology. In subsequent years, the employees of the department Professor V.F. Krylov, Candidates of Medical Sciences L.D. Knyazeva and R.V. Vartanyan, Honored Doctor of the Russian Federation Professor S.G. Cheshik made a huge contribution to the study of the clinic, pathogenesis, diagnosis and treatment viral diseases in the field of respiratory medicine.

Today, the laboratory continues research on the clinical, pathogenetic aspects of acute respiratory viral infections, and issues of effective treatment are being developed.

Every year, during the period of an epidemic increase in the incidence of acute respiratory infections, laboratory staff conduct hospital monitoring of pathogens of acute respiratory diseases as part of the system of epidemiological surveillance and control of influenza and SARS (Rospotrebnadzor Order No. 373 dated March 31, 2005).

Clinical testing of new antiviral agents in the treatment of influenza in adults and children is the main direction of the laboratory's work in recent years. As a result of studies carried out by the laboratory staff, the efficacy of the main domestic antiviral drugs recommended by the Russian Ministry of Health for the treatment of influenza has been proven.

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.

Cell Engineering Laboratory

Managed by Doctor of Biological Sciences, Professor A.A. Kushch.

The laboratory was established in 1986.

For the first time in our country, the laboratory staff developed a hybridoma technology for obtaining monoclonal antibodies (mAb) to viral antigens. The mAb panel for the surface antigen of the hepatitis B virus (HBsAg) was obtained and on its basis the first monoclonal test system was designed in our country for the diagnosis of hepatitis B. The introduction of the developed test system into production made it possible to significantly increase the sensitivity and specificity of the detection of the surface antigen of the hepatitis B virus in the blood serum and to reduce the incidence of post-transfusion hepatitis B.

Currently, the collection of hybridomas obtained in the laboratory includes more than 50 clones producing mAb that interact with proteins of the most common and epidemically significant viruses: hepatitis B and C viruses, herpes simplex virus, human cytomegalovirus, human immunodeficiency virus, tick-borne encephalitis virus, Venezuelan equine encephalomyelitis virus, avian influenza virus, and human influenza virus. Based on mAb, methods of detection and reagent kits have been developed for the detection of hepatitis B virus, hepatitis C virus, tick-borne encephalitis virus, human cytomegalovirus, herpes simplex virus, epidemic and pandemic strains of human influenza viruses. The priority nature of the developments is confirmed by copyright certificates for inventions and patents of the Russian Federation.

MAbs were also used to solve a number of theoretical issues. Using mAb, the fine antigenic structure and topology of the antigenic determinants of the studied viruses were determined, and previously unknown epitopes inducing the formation of virus-neutralizing antibodies and possessing protective properties were identified. The sites of integration of HIV proviral DNA on human chromosomes in HIV-infected cells have been established. The laboratory conducts research aimed at uncovering the cellular and molecular mechanisms of the development of hepatitis C.The effect of human cytomegalovirus on cell proliferation and apoptosis is being studied. Particular attention is paid to a new area in the laboratory's work: the development of DNA vaccines. Multi-epitope compositions have been proposed, the immunogenic and protective properties of two candidate vaccines have been studied: anti-herpes and anti-hepatitis C.A comprehensive study of the role of herpes viruses in the development of infertility, pregnancy disorders, and in the pathology of newborns is carried out.

Over the years of lab existence (1986-2015), the laboratory staff published 270 scientific papers, received nine copyright certificates for inventions, and six patents of the Russian Federation. The laboratory has trained 29 candidates and two doctors of sciences.

Laboratory of Viruses Ontogenesis

Managed by Doctor of Medical Sciences, professor N.N. Nosik.

The laboratory was established in 1969.From the moment of its foundation until 1988, the laboratory was headed by Academician of the Russian Academy of Sciences F.I. Ershov, since 1988 it is headed by Professor N.N. Nosik.

Since the mid-1970s, the study of interferons (IFN) has become the main research topic. In parallel, oncornaviruses were studied, in particular, type D oncornavirus isolated from human cells. Complex studies in collaboration with specialists from the National Cancer Institute (Fort Detrick, USA) established the identity of type D oncornavirus and the Meson-Pfizer monkey virus.

A program was developed to study IFN inducers as promising antiviral drugs. Scientific research is still carried out in two traditional areas: the study of the functioning of the IFN system as part of the cytokine network in viral diseases and the dependence of the effect of therapy on the state of the system. On the other hand, the search for new antiviral drugs continues (including among IFN inducers and immunomodulators, including fullerenes, bitulin), promising classes of active compounds are being studied in vitro and in vivo. In recent years, a third area has been added to the above-mentioned: the study of the virucidal properties of various chemical (classes of compounds) and physical (UV radiation, ozonation) methods of exposure, suitable for inactivation of viruses and their application in various fields of health care.

Using peptide synthesis methods, the group of bioorganic chemistry is searching for and creating antiviral substances against the hepatitis C virus, various genotypes of influenza A and herpes viruses. Research continues on the synthesis of peptide fragments of the IgG hinge region as efficient non-toxic inducers of IFN.

Polyphenolic fractions of the fungus In. Obliquus are studied as a natural object for the inhibition of a number of viruses (influenza A, hepatitis C, herpes, HIV-1).

The laboratory takes an active part in the work of the Testing Laboratory Center for testing and expert evaluation of antiviral agents and disinfectants.

Monographs and patents.

• N.N. Nosik, D.N. Nosik, M.N. Nosik Protect yourself from viruses. MIA, 2010, 112 p.
• D.N. Nosik, N.N. Nosik Prevention of occupational infection with the human immunodeficiency virus. M., 2008, 57 p.
• V.A. Shibnev, T.M. Garaev, M.P. Finogenova, E.S. Shevchenko, E.I. Burtseva Derivatives of 1-(1-adamantyl) ethylamine and their antiviral activity. RF patent RU 2461544 C1, priority dated April 19, 2011
• V.A. Shibnev, P.G. Deryabin, M.P. Finogenova, T.M. Garaev, D.V. Mishin Peptide derivatives of 1-(1-adamantyl) ethylamine and their antiviral action. RF patent RU 2524216 C1, priority dated April 9, 2013

Virus Ecology Laboratory

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

The laboratory was created in 1968 on the initiative of Academician of the Russian Academy of Sciences D.K. Lvov, who had been working as its permanent head for more than four decades. From 2010 to 2014, the laboratory was headed by a student and follower of the ideas of Academician D.K. Lvov, Doctor of Biological Sciences M.Yu. Shchelkanov. In 2014, Candidate of Biological Sciences I.T. Fedyakina was appointed head of the laboratory. The circle of scientific interests includes the study of the antiviral activity and mechanisms of action of chemotherapy drugs against influenza infection in vitro and in vivo caused by strains of the influenza A virus stored in the State Collection of Viruses, as well as avian and human influenza viruses isolated in the laboratory.

Traditionally, the main direction of the laboratory's research is the study of new and re-emerging viral infections with special attention to agents with a high degree of genome variability. Comprehensive studies are aimed at studying the evolution of pathogens. The study of the ecology of pathogens, interpopulation interactions between vertebrate hosts (including humans), viruses, arthropod vectors in a variety of environmental conditions, and analysis of emerging epidemic situations allow predicting future epidemic situations on the territory of the Russian Federation and neighboring countries. The use of molecular genetic methods in this case makes it possible to determine trends in the change in the genetic properties of viral populations, to create conditions for the development of efficient diagnostic and prophylactic drugs. On the basis of an ecological approach, a schematic diagram of the circulation of arboviruses in different climatic zones has been developed. Based on theoretical assumptions, a survey of the territory of Northern Eurasia for arboviruses was carried out. As a result, 69 viruses were isolated, 24 of which were registered in the International Catalog as new to science. Previously unknown infections have been described: Karelian fever, Issyk-Kul fever, Karshi, Tamdy, and the Syr Darya valley fevers. A forecast of epidemic outbreaks in various landscape belts of Russia has been developed. Genetic makeup of the Crimean hemorrhagic fever virus and West Nile virus that caused widespread epidemic outbreaks in 1999–2002 in the South of Russia was determined using the molecular ecology methods. Identity of genomes of West Nile virus strains isolated in that period in Russia and the USA. Over the past three years, together with specialists from the laboratory of biotechnology, for the first time in the world, more than 300 strains of zoonotic RNA-containing viruses belonging to seven families have been genetically characterized. More than 50 of them are described as new types of viruses.

An ecological approach was used to study the mechanisms of the emergence of new pandemic influenza A viruses.Active circulation of 14 different influenza A viruses in natural biocenoses of Northern Eurasia, including genetic variants, which are regarded as possible precursors of new pandemic viruses, has been established.

The genotypic composition of the hepatitis C virus is being monitored on the territory of the Russian Federation. A constant change in the percentage of individual genotypes of the virus, the appearance of recombinant forms of this virus in territories previously free from it have been identified. A new subtype of hepatitis C virus has been discovered.

The laboratory is developing models to assess the efficacy of new drugs and chemical compounds against influenza virus in cell culture and in animals.

The laboratory is characterized by wide intra- and inter-institutional integration. For their work, the laboratory staff was awarded the State Prize of the Russian Federation, the Prize of the Council of Ministers of the USSR, and several D.I. Ivanovsky Prizes of the Russian Academy of Medical Sciences.

Laboratory of the Russian State Collection of Viruses

Managed by PhD in Biological Sciences I.V. Dolzhikova.

The State Collection of Viruses of II-IV Pathogenicity Groups operates on the basis of the D.I. Ivanovsky Institute of Virology of the Federal State Budgetary Institution N. F. Gamaleya National Research Center of the Ministry of Health of Russia. The collection has been operating since the establishment of the institute in 1944. The status of the State Collection of Viruses (SCV) of the Russian Federation and its Charter were approved in accordance with the Decree of the Government of the Russian Federation dated June 24, 1996. In these documents, the SCV was recognized as the heritage of the state, and the need for its mandatory preservation and replenishment was confirmed.

Collecting purposes:

• research
• technological
• educational
• patenting.

Collection specialization:

• ecology
• taxonomy
• biotechnology
• industry
• agriculture / forestry
• medicine
• sanitation
• quarantine
• veterinary medicine.

The total fund of SCV exceeds 30,000 storage units.
Viruses: 2800 strains, over 600 species belonging to 18 families.
RNA-containing viruses: Arenaviridae, Вunyaviridae, Caliciviridae, Coronaviridae, Flaviviridae, Orthomyxoviridae, Paramyxoviridae, Picornaviridae, Rhabdoviridae, Reoviridae, Retroviridae, Togaviridae.
DNA-containing viruses: Adenoviridae, Hepadnaviridae, Herpesviridae, Papillomaviridae, Parvoviridae, Poxviridae. 
The SCV also contains about 60 strains of seven species of chlamydia from two genera: Chlamydia and Chlamydophilia of Chlamydiaceaе family.

Sources of fund formation:

• own developments of employees of the D.I. Ivanovsky Institute of Virology
• research organizations of state and private ownership
• biotechnological enterprises
• field studies of infection foci in the territory of the Russian Federation and the CIS countries.

Deposit criteria:

• original copyright strains
• reference strains
• international standard strains
• recombinant and mutant strains
• experimentally selected strains
• producer strains for obtaining diagnostic and prophylactic drugs.

Preservation methods used:

• lyophilization
• cryopreservation.

The main areas of activity of the SCV are the following:

• Preservation of the gene pool of viruses collected in the territory of Russia and the CIS countries during field investigations of outbreaks of infectious diseases of unknown etiology, as well as those obtained from abroad
• Expansion of the collection with viruses isolated during epidemic (epizootic) outbreaks and presenting problems for Russian healthcare as especially dangerous pathogens or pathogens of socially significant infections that can create emergency epidemic situations unforeseen in their consequences
• Expansion of the collection with viruses for the purpose of subsequent patenting of industrial strains obtained in scientific laboratories and suitable for the production of vaccines, diagnostic drugs on their basis, as well as for screening of antiviral drugs
• Use of viruses stored in the SCV for the development of modern diagnostic products, for obtaining virus-specific immunoglobulins, monoclonal antibodies, serum panels, antigens, genetic material necessary for express indication, diagnosis and identification of viruses in the process of decoding outbreaks of infectious diseases unclear etiology, and for other purposes.
• The use of viruses stored in the SCV for the development of therapeutic and prophylactic drugs, for the creation of experimental models of infections that are important for preclinical trials, for testing disinfectants of various origins, for evaluating the effectiveness of manufactured and developed vaccines against viral infections, for breeding vaccine variants of viruses, and for other purposes
• Use of viruses stored in the SCV to study the evolution and history of the emergence of epidemic strains, to study the variability of virus strains
• Supply of epidemiological institutions, virological laboratories of the country that have official permission to work with viruses of II-IV pathogenicity groups with collection strains of viruses for quality control and improvement of the developed diagnostic and prophylactic drugs and test systems.

Equipment.
The SCV has the necessary equipment for the implementation of all operational and current measures related to the main activity.
The SCV depository is capable of storing more than 100,000 samples at temperatures of -20, -80, -150 or -196°C.
For storage of lyophilized viral material, low-temperature freezers with reduced energy consumption are placed in the SCV storage. Cooling temperature is down to -80°C.
Ultra-low-temperature freezers are used to store liquid frozen viral suspensions. Temperature range is down to -150°C.
There is a cryostorage with liquid nitrogen for storing samples at temperatures down to -196°C.

Biological Safety.
The activity of the SCV is carried out in full compliance with the legislative acts regulating activities related to pathogenic microorganisms of II-IV pathogenicity groups.

International.

• Convention on Biological Diversity (Rio de Janeiro, Brazil, June 3-14, 1992).
• Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure signed in Budapest on April 28, 1977, as amended on September 26, 1980.

Federal.

• Sanitary and epidemiological rules "Safety of work with microorganisms of I-II groups of pathogenicity (hazard)".
• Sanitary and epidemiological rules "Procedure for issuing a sanitary and epidemiological conclusion on the possibility of working with pathogens of human infectious diseases of I-IV groups of pathogenicity (hazard), genetically modified microorganisms, poisons of biological origin, and helminths."
• Sanitary and Epidemiological Rules "Procedure for recording, storage, transfer and transportation of microorganisms of I-IV pathogenicity groups".
• Sanitary and Epidemiological Rules "Safety of work with microorganisms of III-IV pathogenicity groups".

Departmental.

• Rules for depositing and issuing microorganisms (viruses, prions, and chlamydia).
• Regulation on the State Collection of Viruses.

Physical security.

The SCV has a security, monitoring and warning system in case of emergency situations.

Information Security.

A protected local computer network is established in the SCV.

The result of the existence and activity of the SCV is the solution of fundamental issues of biological safety associated with the study of new and recurring infections, viruses with a high degree of genome variability, which have an increased epidemic hazard, on the problem of socially significant infections.

A number of applied tasks are being solved within the framework of the SCV activity.

• Recommendations on optimal conditions for conservation and long-term storage of viral strains were developed and published.
• To conduct environmental and epidemiological monitoring on the territory of Russia, based on viral strains stored in the SCV, new diagnostic preparations and test systems for diagnosing a number of especially dangerous arbovirus infections circulating in the Russian Federation have been created and their production has commenced.
• Virus strains characterized by properties suitable for practical use are being patented.
• On the basis of viral strains stored in the SCV, new drugs have been created for the treatment of dangerous and socially significant infections (AIDS, herpesvirus infections).

Leukemia Virus Laboratory

Managed by Doctor of Biological Sciences M.R. Bobkova.

The team and the area of the laboratory's activities were formed more than twenty years ago, when studies of the molecular epidemiology of HIV infection in Russia were just beginning and were based on the use of now outdated methods, including serological analysis, which gives only an approximate and inaccurate assessment of the spread of HIV variants, and heteroduplex DNA analysis. Since then, the laboratory has come a long way in improving the material and technical base, methodological approaches, staff, and work content.

The laboratory now has its own sequencing equipment and the necessary software. Therefore, all work on genotyping is carried out only on the basis of sequencing the sequences of the HIV genome, which makes it possible to fully assess the features of the HIV genome, and to carry out phylogenetic and philodynamic analysis. This resulted in a transition to a modern level of research, comparable to that in Western laboratories.

The works of recent years have been devoted to the analysis of genetic variants of HIV at a new stage in the development of the epidemic, when its scale has become threatening, and almost all groups of the population have become vulnerable to infection. The studies were carried out both in different geographic regions of Russia and the CIS countries, including those previously not surveyed (the Far East, Armenia, Kyrgyzstan), and in different risk groups of infection (drug addicts, heterosexuals, men who have sex with men). The main genomic target of research was the structural genes of HIV – gag, env, and pol. In the past few years, the laboratory has been actively involved in the problem of HIV drug resistance. It has been shown that a unique genetic variant of HIV-1 subtype A, originating from Central Africa, predominates in most areas; however, the pattern of the variants distribution shows marked tendencies to change. The main one is the increasing spread of recombinant forms of the virus, and mostly – CRF02_AG and CRF03_AB, which are found in all risk groups of infection.

The laboratory has developed a methodology for collecting and transporting HIV samples from the regions, established contacts with regional laboratories and the biological samples carrier WorldCourier. Freezing equipment for storing collections is available. A unique database of genotyping results for Russian HIV-1 strains, similar to Western databases, has been created. There are strong contacts with foreign scientists in Europe and the United States, which resulted in the integration of data into international algorithms for their interpretation, in particular – EuResist (http://www.euresist.org) and NCBI (http: //www.ncbi.nlm. nih.gov).

The lab has a state permit for the collection of blood samples from HIV-infected patients; the permit is issued by the Ethics Committee in 2013 and extends to all types of research in the territory of the Russian Federation.

The laboratory staff takes an active part in the activities of the practical health care system; over the past three years, with the support of the European Union grant N223131 CHAIN ​​and pharmaceutical companies manufacturing antiretroviral drugs, about 20 seminars on the problem of HIV drug resistance were held in many medical and preventive institutions and AIDS-centers in Russia and the CIS countries, with the total participation of more than 800 specialists – doctors, epidemiologists, and laboratory technicians. For patients, “Substitution of Therapy and Drug Resistance” booklet has been translated, posted on the Internet and prepared for publication (http://ibase.info/замена-терапии-и-лекарственная-устой/). In April 2014, M.R. Bobkova's monograph “HIV Drug Resistance” was published and received a vivid response from many specialists from Russia and the CIS countries.

Influenza Ecology and Epidemiology Center

Managed by RAS academician D.K. Lvov.

The D.I. Ivanovsky Institute of Virology has more than half a century of experience in monitoring the circulation of influenza viruses, a great contribution to the study of the properties of which was made by the scientists who were the first ones to study this problem: Honored Scientist of the RSFSR, Professor M.I. Sokolov and Professor A.S. Gorbunov. In 1959, the All-Union Center of the USSR for Influenza was created at the Institute, collaborating with the WHO, headed by outstanding scientists of the country: Academician of the USSR Academy of Medical Sciences V.M. Zhdanov, and later by Honored Scientist of the RSFSR, Professor L.Ya. Zakstelskaya. Since 1987, Academician of the USSR Academy of Medical Sciences (later - RAMS, then RAS) D.K. Lvov was elected director of the Institute of Virology, who also managed the center.

Influenza Center Archives

Laboratory of Molecular Diagnostics

Managed by Corresponding Member of the RAS T.V. Grebennikova.

The laboratory is studying the genomes of viruses and bacteria that cause anthropozoonoses. Phylogenetic studies are being carried out to study the spread of viruses in various regions of the Russian Federation.

The laboratory uses methods of molecular biology, epidemiology, immunology, genetic and cellular engineering for the development and creation of immunobiological preparations. Diagnostic test systems based on PCR and ELISA have been developed and put into practice to detect a number of viral pathogens and virus-specific antibodies.

PCR-based test systems have been developed for the detection of influenza A virus of various subtypes, rabies virus, rotaviruses, coronaviruses, arteriviruses, as well as mycobacteria, such as for the differentiation of M. tuberculosis and M. bovis; pathogenic bacteria B. anthracis.

On the basis of the recombinant antigens obtained in the laboratory, ELISA test systems have been developed to determine viral antigens and antibodies to influenza A virus, arteriviruses, rotavirus and coronavirus.

For the study of RNA-containing viruses, a modern approach is used, aimed at modifying the viral genome by the method of synthesis of infectious viral genomes (reverse genetics). Within the framework of this direction, infectious copies of arteriviruses, pestiviruses, influenza A virus were obtained. Several recombinant influenza A viruses of various subtypes with desired properties were obtained.

Cell culture applications

Before you decide to use cell culture as an object or research tool, you must make sure that the benefits that you get will outweigh the difficulties associated with this method.

Laboratory for Chronic Viral Infections

Managed by Doctor of Medical Sciences L.B. Kisteneva.

The laboratory was organized in 1981 and until 2013 was managed by the Honored Scientist of the Russian Federation, Corresponding Member of the Russian Academy of Medical Sciences I.V. Shakhgildyan. The original name of the laboratory was the Laboratory of Epidemiology and Prevention of Viral Hepatitis. In 2008, the functions of the laboratory were expanded and it received its current name.

The main direction of scientific research was to clarify the main epidemiological patterns of different types of viral hepatitis, to determine the dynamics and manifestations of the epidemic processes of hepatitis A, B, C, and D.Particular attention was paid to establishing the frequency and characteristics of perinatal transmission of hepatitis B and C.

An important section of the work was the development and implementation of hepatitis B vaccine prevention programs, the study of its efficiency, which made it possible to control the incidence of viral hepatitis B.

In recent years, the tasks of the laboratory have expanded. The monitoring of the etiological structure of viral hepatitis A, B, C, D, E, and G has been developed. The main attention is paid to the study of the clinical features and outcomes of viral hepatitis C, increasing the efficiency of its treatment.

A significant place in the work of the laboratory in recent years is occupied by the study of clinical and laboratory features of cytomegalovirus infection in women of childbearing age, pregnant women and newborns; development of a system of therapeutic and prophylactic measures. The implementation of these tasks will contribute to a favorable course of pregnancy and the prevention of perinatal pathology.

Corresponding Member of the Russian Academy of Medical Sciences I.V. Shakhgildyan, Candidate of Medical Sciences D.M. Braginsky, and Professor S.G. Cheshik

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.

Laboratory of the structure and morphogenesis of viruses

Managed by Doctor of Biological Sciences, Professor A.A. Manykin.

The first head of the morphological laboratory at the Institute of Virology was Professor E.I. Turevich, who, while still a student at the University of Warsaw, worked at the department headed by D.I. Ivanovsky and carried out his first scientific work. E.I. Turevich made a significant contribution to the study of cell pathology in a number of viral infections, especially in rabies. After E.I. Turevich, for more than eight years the laboratory has been headed by Professor A.A. Avakyan.

From 1959 to 2016, the laboratory has been headed by Academician S.M. Klimenko. Electron microscopy has become the main research method. The laboratory uses the whole range of existing techniques for transmission and scanning electron microscope in the study of the morphogenesis of viruses, the structure of the virion, proteins and nucleic acids. Priority data have been obtained on the organization of DNA in the head of T-even phages, which to the maximum extent explain the mechanism of DNA ejection. For the first time, data were obtained on the organization of the ribonucleoprotein of the influenza virus into a coiled, integral structure containing all eight RNA segments.

In cooperation with the Laboratory of Virus Ecology, an indication was carried out within the family of many arboviruses isolated in the USSR, which made it possible to significantly accelerate the study of a number of viruses new to science. The participation of Academician S.M. Klimenko in these studies was marked with the State Prize of the Russian Federation in 1999.

The laboratory has made a significant contribution to the study of HIV infection. The core of the laboratory is high-level professionals — leading researchers E.A. Gushchina and A.A. Manykin. In the end of 2016, after Academician S.M. Klimenko passed away, the laboratory was headed by Professor A.A. Manykin.

In recent years, intensive research has been carried out using the in situ PCR method to detect papillomavirus type 16 and 18 DNA in cervical cancer biopsies and the hepatitis C virus genome in liver biopsies using in situ real-time PCR. Along with electron microscopy, the laboratory uses an atomic force microscope.

At different times, the laboratory staff defended four doctoral and 16 master's theses.

Laboratory of viral pathogenesis

Managed by Corresponding Member of the RAS O.P. Zhirnov.

The laboratory was founded in 1992.Based on a combination of classical virological approaches and modern methods of molecular biology and genetic engineering, the laboratory studies the mechanisms of viral pathogenesis and cellular pathology caused by viruses. The basics of cell apoptosis and necrosis in viral infections are investigated, the mechanisms of viral replication and attenuation are studied. The laboratory is involved in the development of drugs against cancer based on the design of artificial viruses that selectively kill cancer cells. The main object of study is the RNA-containing enveloped viruses (orthomyxoviruses, paramyxoviruses). Since 1992, the laboratory has published about 30 scientific papers in leading domestic and international journals. In 1997, the laboratory was awarded the Moscow Mayor's Administration Diploma for the development of a new method of treating influenza and acute respiratory infections. The laboratory carries out a number of international projects with Philipps University (Germany), Vanderbilt University (USA), and Howard Hughes Medical Institute (USA).

Influenza Etiology and Epidemiology Laboratory

Managed by Doctor of Medical Sciences E.I. Burtseva.

The research that are currently being carried out in the laboratory were initiated by Honored Scientist of the RSFSR, Professor M.I. Sokolov, Professor A.S. Gorbunova, Academician of the USSR Academy of Medical Sciences V.M. Zhdanov, Honored Scientist of the RSFSR, Professor L.Ya. Zakstelskaya, Honored Scientist of the Russian Federation, Professor A.N. Slepushkin.

In accordance with the order of Rospotrebnadzor No. 373 dated March 31, 2005 "On improving the system of epidemiological surveillance and control of influenza and acute respiratory viral infections", the laboratory was assigned the functions of the Center for Ecology and Epidemiology of Influenza (CEEI). In order to further implement the International Health Regulations (IHR 2005) on the territory of the Russian Federation, by the order of Rospotrebnadzor No. 88 dated March 17, 2008 "On measures to improve monitoring of pathogens of infectious and parasitic diseases", he laboratory was assigned the functions of one of four Reference Centers for influenza monitoring in the Russian Federation.

The laboratory conducts research to study the antigenic, biological and molecular-genetic properties of circulating strains of influenza viruses using the following methods: isolation of strains on MDCK tissue culture cells and chicken embryos, hemagglutination reaction, hemagglutination-inhibition reaction, ELISA, microneutralization, PCR and PCR-RT. Animal models are used to obtain immune sera. The State Collection of Viruses is being replenished with samples of original epidemic and pandemic strains.

Every week, the laboratory analyzes the incoming data on the incidence of influenza and SARS in different age groups and laboratory diagnostics data in certain territories of the Russian Federation, which are summarized, formalized and submitted to the Ministry of Health of Russia, Rospotrebnadzor, Research Institute of Influenza, and collaborating healthcare institutions.

The laboratory is entrusted with the functions of the National Influenza Center (NIC) collaborating with WHO. Within the framework of international cooperation, data on laboratory diagnostics, reference strains, epidemic strains and diagnostic products are exchanged between the laboratory and the WHO Collaborating Centers for Influenza (London, UK; Atlanta, USA). Every year, according to WHO recommendations, the laboratory participates in proficiency tests of the quality of the studies performed to confirm the status of the NIC.

Fundamental practical research on the use of nanotechnology for the diagnosis and prevention of influenza and ARVI is being carried out.

Chronic viral infections laboratory

Managed by Doctor of Medical Sciences, professor D.N.Nosik.

The main areas of research are:

• Study of the properties of immunodeficiency viruses.
• Preclinical expert evaluation of the antiviral efficacy of compounds of various natures for the prevention and treatment of the disease caused by the immunodeficiency virus.
• Research and expert evaluation of disinfectants on the model of regulatory test viruses.

On the basis of the laboratory, there is an accredited Testing Laboratory Center of the D.I. Ivanovsky Institute of Virology for testing antiviral agents and disinfectants.

Accreditation certificate No. ГСЭН.RU.ЦОА.315.

State registration No. РOCC.RU.0001.513126.

The center conducts trials for preclinical study of antiviral drugs as well as the study and expert assessment of the virucidal properties of disinfectants proposed for use in the Russian Federation.

Laboratory for Molecular Pathogenesis of Chronic Viral Infections

Managed by Doctor of Biological Sciences, Professor G.A. Galegov.

The laboratory was created as Laboratory for Chemotherapy of Viral Infections in 1963 on the initiative of Academician of the USSR Academy of Medical Sciences V.M. Zhdanov, and in October 2020 was transformed into Laboratory for Molecular Pathogenesis of Chronic Viral Infections by adding specialists which earlier formed the staff of the Group of Chemistry of Viral Nucleic Acids. Since 1965, the laboratory has been headed by Professor G.A. Galegov.

The main areas of the long-term fundamental and applied scientific activity of the laboratory are as follows:

• Studies of the antiviral action of compounds of the adamantane series in influenza and alphavirus infections. The laboratory staff took an active part in the work of the inter-institute team of specialists on the creation and uptake of rimantadine, which has become internationally known.
• The principles of combined chemotherapy of viral infections based on the use of drugs with different mechanisms of action on models of influenza and herpesvirus infections have been developed.
• Long-term studies to study the antiviral effect of modified nucleosides – inhibitors of nucleic acid synthesis.
• Development of new ways to suppress the reproduction of influenza A viruses and herpes simplex virus with drug resistance. Direct isolation of such viruses from clinical material. As a result of extensive preclinical studies, two new classes of antiherpetic substances were discovered and investigated in detail – bis-netropsin derivatives and phosphorus-containing analogs of acyclovir, which simultaneously have high activity against drug-resistant herpes virus. The molecular mechanism of their antiviral action has been disclosed. The results are widely presented in scientific Russian and English-language periodicals.
• Participation of laboratory staff in the creation of drugs for the treatment of HIV infection and AIDS: a domestic version of azidothymidine – thymazide and a new drug – phosphazide (nikavir), for which patents have been obtained in Russia, the USA, Japan, and a number of European countries. In 1986, Professor G.A. Galegov was awarded the Prize of the Council of Ministers of the USSR for the development of means for the herpesvirus infection treatment, and in 2000 – the State Prize of the Russian Federation for the development of antiviral drugs (anti-HIV).

Highly qualified and highly educated employees worked in the laboratory in different years and continue working today – N.F. Pravdina, N.L. Pushkarskaya, S.V. Lavrov, V.M. Shobukhov, N.D. Lvov, I.G. Petrova , N.A. Leontieva, T.V. Veselovskaya, V.L. Andronova, T.Yu. Kilesso. The laboratory has trained 24 candidates and three doctors of sciences. The laboratory staff received 42 patents and copyright certificates, published about 450 papers.

Laboratory of Applied Virology and Biotechnology

Managed by Doctor of Biological Sciences, Professor A.В. Zaberezhny.

The laboratory is engaged in the creation of specific components of test systems for the diagnosis of viral anthropozoonoses, as well as other immunobiological preparations. Modern approaches are used to obtain hybridomas producing monoclonal antibodies (mAb) to various viral antigens.

An example of the latest developments of the laboratory is the production of mAb to the nucleocapsid protein of the influenza A virus, to the rabies virus, and prion proteins. To obtain mAb, recombinant proteins obtained in prokaryotic or baculovirus expression systems are used.

Anti-species immunoperoxidase conjugates for use in diagnostic test systems have been obtained. Currently, work is underway to obtain mAb for surface antigens of pestiviruses in order to create a comprehensive system of differential diagnostics against the background of the use of new generation labeled vaccines. The laboratory is involved in the creation and characterization of recombinant viruses obtained by reverse genetics.

Cell culture collection

Hela and Hela-like lines

1 Hela Cervical carcinoma
2 Hela lhm Cervical carcinoma
3 Detroit-6 Bone marrow of a patient with lung cancer
4 Hep-2 Epidermal carcinoma of the larynx
5 RH Embryonic kidney
6 J-96 Blood of a white male with subacute leukemia
7 FL Amnion
8 KB Epidermal carcinoma of the oral cavity
9 U Amnion
10 L 132 Embryonic lung
11 Chang conjunctiva Normal conjunctiva
12 Chang liver

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.

Virus Physiology Laboratory

Managed by PhD in Biological Sciences T.A. Timofeeva.

Until 1987, the laboratory was headed by Academician of the USSR Academy of Medical Sciences, director of the D.I. Ivanovsky Institute of Virology from 1961 to 1987, Viktor Mikhailovich Zhdanov. During this period, the scientific topics researched by the laboratory were very diverse. In the 1960s, the mechanisms of viral reproduction were studied, first by inhibitory analysis, and since 1967 — by molecular biological methods. During this period, replicative forms of RNA of paramyxoviruses were discovered and analyzed, with the direct participation of V.M. Zhdanov in experimental work, and virus-specific informosomes were described. In subsequent years, the range of models was significantly expanded. A large series of studies on mammalian oncoviruses was carried out, and an endogenous porcine virus was first discovered. The cellular origin of oncogenes of retroviruses was proved, studies of type D oncoviruses were carried out. Integration of the genome of non-oncogenic viruses (measles virus) was shown. During this period, the laboratory also conducted molecular biological studies of the hepatitis A virus.

Research on the human immunodeficiency virus (HIV), which has been actively pursued at the Institute of Virology since the early 1980s, was also started in the laboratory of viral physiology. In the course of these studies, a highly productive line of HIV-producing cells was obtained, the first diagnostic test system in the USSR was developed to detect the virus and antibodies to HIV, and laboratory production was organized for the release of the country's first batches of diagnostic kits. Later, the production was transferred to Novosibirsk, to NPO Vector, which has been producing the test system to this day.

For many years, starting in the 1960s, the laboratory has been studying the molecular biology of the influenza virus. In 1977, for the first time, the molecular biological characterization of the virus that caused the global epidemic of 1977 ("Russian flu") was carried out, and for the first time ever the antigenic variability of the virus when changing the host was shown. This area (molecular biology and molecular genetics of influenza viruses) has become the priority for the laboratory since 1987, when Professor N.V. Kaverin became the head of the laboratory after the death of V.M. Zhdanov. Since that time, work has been carried out in the laboratory to study the functional interaction of the genes of hemagglutinin and neuraminidase of influenza A viruses. For the first time, post-reassortational changes in hemagglutinin were described, which expanded the understanding of the evolutionary processes of influenza viruses. After the data on the three-dimensional structure of hemagglutinin of the H5 and H9 subtypes based on the results of X-ray crystallographic analysis were published, the laboratory for the first time ever performed a detailed mapping of the antigenic structure of hemagglutinin of these subtypes, which made it possible to identify the correspondence between the features of the distribution of antigenic regions and variations in the three-dimensional structure of hemagglutinin of various subtypes. After the emergence and spread of the 2009 H1N1 pandemic virus, the positions of amino acid residues recognized by monoclonal antibodies against the A/IIV-Moscow/01/09 (H1N1) pdm09 strain, the first 2009 pandemic strain isolated in Russia, were mapped in the Department of Ecology of Viruses of the D.I. Ivanovsky Institute of Virology. In addition to hemagglutinin mapping, a relationship was shown between such characteristics of the virus as antigenic specificity, virulence, and receptor activity. In our studies, for the first time, mapping of the protein regions of the influenza A virus nucleoprotein, which differ in different strains and are recognized by antibodies, has been carried out. For the first time, an antigenic site associated with a host circle has been identified in the influenza A virus nucleoprotein protein molecule. The localization and structure of the compact antigenic site of the nucleoprotein protein of the influenza A virus has been disclosed. The works performed in the laboratory have been published in leading Russian and international scientific journals and are widely cited in the scientific literature.

After 2010, one of the main areas of scientific activity of the laboratory under the leadership of Academician of the Russian Academy of Sciences N.V. Kaverin was associated with solving the problem of the ratio of variations in the antigenic structure of influenza A virus proteins and the evolution of the functional properties of viral proteins. The main objectives of the study were to identify the effect of mutations in the hemagglutinin of influenza A virus, which provide resistance to monoclonal antibodies, on the phenotypic properties of hemagglutinin, as well as to identify varying antigenic epitopes in the structure of the influenza A virus nucleoprotein protein.

After the death of an outstanding virologist and molecular biologist, Academician of the Russian Academy of Sciences Nikolai Veniaminovich Kaverin, the laboratory continues the cycle of these studies. The data obtained play an important role in understanding the processes of the emergence and adaptation of pandemic strains that acquire various combinations of genes from mammalian and avian influenza viruses, as well as the mechanisms of regulation of virulence and specificity of influenza viruses in relation to the host. Research on the use of reassortment of human and avian influenza viruses has been applied to obtain highly productive vaccine strains. They are directly related to the disclosure of the mechanisms of the influenza virus variability at the molecular level and are the most important achievement of Russian and world virology.

Laboratory of Molecular Genetics

Managed by Doctor of Biological Sciences A.G. Prilipov.

The laboratory was founded in 1987 under the leadership of Doctor of Biological Sciences V.V. Mesyanzhinov. Initially, the laboratory worked mainly with T4 bacteriophage and was engaged in the study of proteins of the basal lamina, fibrillar components of the bacteriophage, and genes encoding these proteins. The complete nucleotide sequences of at least 20 genes of the T4 bacteriophage were determined, systems for the expression and purification of protein products were worked out, and the properties of proteins were determined. Work has begun on determining the tertiary structure of proteins with the expectation of using some of them, in particular, the product of the wac gene, as carrier proteins of antigenic determinants of human and animal viruses.

In 1997, Dr. A.G. Prilipov became the head of the laboratory. At that time, the interests of the laboratory focused on the hepatitis C virus.The complete primary sequence of the 1b genotype C hepatitis virus was determined (for the first time in Russia). A plasmid carrying the complete nucleotide sequence of this variant of the virus was obtained (for the first time in Russia). Expression constructs have been obtained that allow the production of structural proteins of this virus (core, E1, E2).

In 2000, the laboratory began working with West Nile virus. The complete nucleotide sequences of 14 genomes of the virus were determined from the collection of the D.I. Ivanovsky Institute of Virology, including those for the Indian genotype of the virus – for the first time in the world. Also, for the first time in the world, the 4th genotype of West Nile virus was discovered, and its complete nucleotide sequence was determined. Subsequently, RT-PCR test systems for the detection of virus RNA and a genotyping system for determining group affiliation were designed. These test systems have been debugged and are successfully used to detect field material (including pools of mosquitoes and ticks). To date, at least 2,000 samples of field material have been examined using these instruments for the presence of West Nile Virus RNA. Work was carried out to determine the nucleotide sequence of viruses from positive samples, and their phylogenetic analysis was carried out. Over the past 10 years, the laboratory has worked mainly in two directions: determination of the nucleotide sequences of the genomes of new arboviruses and the influenza virus.

For arboviruses, for the first time in the world, the complete genome sequences were determined and the classification for the Kiasanur forest disease virus, Karshi virus, and white hare virus was refined. A new virus from the California encephalitis serocomplex has been discovered and named the Khatanga virus. Five different genotypes have been found for it; intraspecific and interspecific reassortment is shown.

For the H5N1 avian influenza virus, most of the complete genomes in Russia were obtained, and various genetic lines of the virus that penetrate into the territory of the Russian Federation were described.

For the pandemic H1N1 influenza virus, a lot of work has been done to determine the whole genome nucleotide sequences, and monitoring of the emergence of new mutations that affect drug resistance, adaptation of the virus to humans and the severity of the disease it causes is constantly carried out.

A large number of RT-PCR test systems, including real-time ones, have been designed to facilitate screening of material for the presence of significant changes in the virus genome. A reverse genetics system is used to test the functional significance of substitutions in the genome.

At the same time, the characteristics description of the spread of the New Castle disease virus (NDV) on the territory of the Russian Federation and neighboring countries was drawn up.

The laboratory is conducting research to develop a universal approach for creating vaccines against flaviviruses using reverse genetics.

Tissue Culture Laboratory

Managed by Doctor of Biological Sciences M.М. Mezentseva.

On the basis of the laboratory, the Collection of Animal and Human Cell Cultures is maintained, which includes more than 150 certified cell lines that are widely used in virology and biotechnology. All certified lines are included in the catalog of the All-Union Collection of Cell Cultures (1991) and the European Catalog of Human and Animal Cell Lines (1993). The laboratory has created a working and seed pools of the vaccine cell line Vero (B), characterized according to the WHO requirements, which can be used for the preparation of viral vaccines and test systems. An antiherpetic vaccine is currently being produced on the basis of this line.

To preserve the gene pool of collection cultures, an automatic freezer Minicool LC-40 made by CFRO (France) is used, which provides standardization of cryopreservation and long-term storage conditions.

Key areas of business:

• determination of optimal conditions for cell cultivation (use of conditioned environments, identification of non-toxic native embryonic bovine sera by determining their toxicity by the MIT24 method and proliferative activity by the MTT method)
• application of methods of cell metabolism inhibition (MIT24 and MTT) to determine the toxicity of biological or chemical substances on a highly sensitive diploid culture of lung cells of the human embryo
• determination of various contaminants (mycoplasma, diarrhea virus) in cell cultures using karyological and cytological, virological (hemadsorption reaction) and molecular biological (PCR) methods
• certification of new cell cultures in accordance with the requirements of the "Guidelines for the certification of transplanted cell lines-substrates for the production and control of medical immunobiological preparations" (RD 42-28-10-89)
• the use of cell cultures for research in the field of nanotechnology (nanoparticles, nanosorbents, nanotubes)
• creation of mini-banks for working with a homogeneous population of cells- an annual practical training on the job "Course on the basics of primary and transplantable cell lines cultivation ".

A collection of cell cultures is available at cells.virology.ru.
Hela and Hela-like lines.
Human cell lines not contaminated with Hela cells.
Human diploid cell lines.
Human lymphoblastoid cell lines.
Transplantable animal cell lines, lymphoblastoid animal cell lines.
Transplantable monkey cell lines.
Transplantable mouse cell lines.
Plasmacytoma (myeloma) of the mouse.
Transplantable hamster cell lines.
Transplantable pig cell lines.
Transplantable cattle cell lines.
Transplantable rabbit cell lines.
Transplantable rat cell lines.
Transplantable cell lines of a different origin.

Immunochemistry Laboratory

Managed by Doctor of Biological Sciences, Professor E.V. Karamov.

The laboratory was created in 1995 at the D.I. Ivanovsky Research Institute of Virology under the leadership of Professor E.V. Karamov. Since that time, the laboratory staff have worked a lot to study the molecular and epidemiological characteristics of HIV-1 variants circulating in the territory of the Russian Federation and neighboring countries. Using the methods of comparative analysis of genetic sequences (genotyping) and the study of immunological properties (serotyping), HIV-1 variants circulating among drug addicts administering drugs intravenously identified in Russia, Ukraine, and Belarus were characterized. During the same period, the laboratory participated in the creation of the first domestic test system for the detection of HIV-1.

Research related to the prevention and treatment of HIV/AIDS is currently underway. Natural and synthetic compounds are being actively studied in order to create new anti-HIV drugs capable of suppressing HIV infection caused by viruses resistant to drugs used in treatment. The revealed low-toxic and highly efficient compounds are included in the Microbicides research program for the development of new immunobiological drugs designed to limit the sexual transmission of HIV. The second important direction in the laboratory's work is the development and evaluation of the efficacy of candidate anti-HIV/AIDS vaccines. One of the first domestic candidate anti-HIV vaccines "HIVREPOL", developed in cooperation with the State Research Center "Institute of Immunology" of the FMBA of Russia, has passed the 1st phase of clinical trials.

Laboratory of Genetically Engineered Drugs

Managed by Doctor of Biological Sciences L.I. Nikolaeva.

The laboratory was founded in 1986 under the leadership of Professor R.A. Gibadulin. The main area of work was defined as the creation of vector systems for the expression of recombinant viral antigens.

In the period from 1986 to 1996, modified vaccinia virus strains expressing the hemagglutinin group of the virus, HBs antigen of hepatitis B virus and a number of HIV-1 proteins were designed. Two authorship certificates and a patent were obtained for recombinant vaccinia strains synthesizing HBs-antigen of hepatitis B virus and HIV-1 Gag-Pol protein. The HBs antigen-producing strain was used in the production of a diagnostic test system at the NPO Vector (Novosibirsk).

In subsequent years, producer strains were constructed in a more promising system using the baculovirus genome as an expression vector in insect cell cultures Sf 21, Sf 9, Hi 5.

In the 2000s, strains producing various proteins of HIV-1 were designed, which made it possible to study individual stages of the morphogenesis of this virus and to establish the interaction of regulatory proteins Vif and Vpr with viral structural proteins and cellular structures. In collaboration with specialists from the George Washington University (USA), new data on the mechanism of interaction between the heat shock protein Hsp-70 of the cell and the regulatory protein Vpr of HIV-1 were obtained. In joint studies with the Laboratory of Leukemia Viruses of the Institute and the Laboratory of Immunology of Tel Aviv University, the development of an autoimmune response to the CD4 molecule in HIV-infected individuals has been shown.

Since 2006, under the leadership of Dr. L.I. Nikolayeva, the laboratory has been working on the production and analysis of recombinant proteins of the hepatitis C virus. Since 2009, studies have begun to analyze the role of the hepatitis C virus polymorphism and the IL28B gene in infected people. Together with the staff of the Faculty of Fundamental Medicine, Lomonosov Moscow State University, the role of polymorphism of eight more human genes in the development of liver fibrosis and the realization of the effects of antiviral therapy was analyzed. Currently, together with specialists from the Pirogov Russian National Research Medical University, the Department of Infectious Diseases of the Russian Medical Academy of Postgraduate Education, and the Center for Bioengineering of the Russian Academy of Sciences, research is being carried out to study the characteristics of the immune response to antigens of the hepatitis C virus.

Over the past five years, the laboratory staff published 14 articles in domestic and foreign journals, received a patent, wrote a manual, defended two Ph.D. theses.