History of the D.I.

History of D.I. Ivanovsky Institute of Virology.

A year was left till the end of the war when Regulation No. 797 of the Council of People's Commissars dd. June 30, 1944 was adopted to establish the Academy of Medical Sciences of the USSR to include the Institute of Virology opened at the premises of the Virology Department of A.M. Gorky All-Soviet Union Institute of Experimental Medicine. The institute was named after D.I. Ivanovsky, the originator of virology, by Regulation No. 4344 of the Council of Ministers of the USSR dd. October 19, 1950. Professor Y.I. Turevich, a follower of D.I. Ivanovsky, was working at the institute for 16 years. V.L. Ryzhkov, a correspondent member of the Academy of Sciences of the USSR, was working there at the same time. His monograph titled Viral Diseases of Plants is still relevant nowadays.

The first director of the institute was professor A.T. Kravchenko. In six years he was transferred to a large virology center of the Ministry of Defense of the USSR as a chief research officer. The first deputy director for science was L.A. Zilber, a member of the Academy of Medical Sciences of the USSR. After joining N.F. Gamaleya Center of Epidemiology and Microbiology, he arranged a large virology department there. For some time the Institute of Virology was headed by A.A. Smorodintsev, a member of the Academy of Medical Sciences of the USSR, who, along with L.A. Zilber, stood at the origin of studying sudden outbreaks of tick-borne and Japanese encephalitis in the Far East and epidemic nephritis. Later, in Leningrad A.A. Smorodintsev established the Institute of Influenza and became its head. The reason for this was quite serious – appearance of the new pandemic virus. However, the Institute of Virology always paid much attention to influenza researches. One of the first deputy directors for science was V.D. Solovyev, a member of the Academy of Medical Sciences. He was one of the constellation of brilliant virologists along with L.A. Zilber, M.P. Chumakov, A.K. Shubladze, E.N. Levkovich, and many other enthusiasts who studied the nature of the mysterious and then deadly virus later called tick-borne encephalitis in the Far East taiga facing a huge risk. Later, V.D. Solovyev became the head of the Virology Department of the N.F. Gamaleya Center of Epidemiology and Microbiology. For a long time he headed the Hygiene, Microbiology, and Epidemiology Division of the Academy of Medical Sciences of the USSR.

Academician Z.V. Yermolyeva, the developer of Russian penicillin, also worked in the Institution of Virology. Her contribution to saving the wounded and their return to the front line cannot be overestimated. During the five years when the Institute of Virology was headed by M.P. Chumakov, a member of the Academy of Medical Sciences, its connections with the research and practical institutions from other regions of the country were significantly growing to result in conducting complex studies and establishment of a training system for virologists. In 1955, M.P. Chumakov established the Institute of Poliomyelitis and Viral Encephalitides, currently bearing its name. Arrangement of the new institute separated from the Institute of Virology was conditional upon the dictates of the time. The country as well as the whole world was affected by dreadful epidemies of poliomyelitis.

After M.P. Chumakov the Institute of Virology was headed by P.N. Kosyakov, a member of the Academy of Medical Sciences of the USSR. A regional center of influenza was established to consolidate 19 regional facilities. Later, it was transformed into the WHO Influenza Center. In 1959, the first building in today's site was commissioned and the institute moved there from the site of the former All-Soviet Union Institute of Experimental Medicine. In 1956, a museum of viral strains was established to be later transformed into the State Collection of Viruses, currently being a national estate.

From 1961 to 1987, the Institute of Virology was headed by V.M. Zhdanov, a member of the Academy of Medical Sciences of the USSR, having established a modern and world-renown research center. The staff has grown twofold and a school of thought in molecular virology was established. The second building and then the third one were put up, a clinical virology and viral hepatitis division was established at the premises of the First City Hospital of Infectious Diseases, six WHO centers were opened (for influenza, arboviruses, viral ecology, herpes, viral hepatites, AIDS). He established the Problems of Virology journal. After the AIDS, the 20th century plague, emerged, V.M. Zhdanov consolidated several laboratories of the institute to study the HIV. The first virus strains in the country were isolated here to become a basis for development of Russian test system. V.M. Zhdanov's outstanding achievement is deemed development of a scientific-based program for global smallpox eradication he brought forward as the USSR's suggestion at the General Assembly of the WHO in 1958. And, in 1980, the WHO declared smallpox eradicated all over the world. V.M. Zhdanov, together with D. Melnik, P. Wildy, and N. Oker-Blom organized a virology section of the International Union of Microbiological Societies. Sustainable connections were built with virologists from 30 countries. This cooperation was successfully developing even in the hardest periods of the cold war.

Personnel for research and practical virology divisions in the USSR and Russia was actively trained via doctoral and post-gradual studies and internships and in the course of conducting joint complex research.  Among these post-graduate students there were future directors and deputy directors of research institutes and members of the Academy of Medical Sciences of the USSR (later – the Russian Academy of Medical Sciences) – B.F. Semenov (I.I. Mechnikov Institute of Vaccines and Serums), S.G. Drozdov (M.P. Chumakov Institute of Poliomyelitis and Viral Encephalitides), V.A. Lashkevich (M.P. Chumakov Institute of Poliomyelitis and Viral Encephalitides), S.G. Dzagurov (L.A. Tarasevich State Institute of Standardization and O.G. Andzhaparidze (Institute for Viral Drug Research named after the scientist after his death). In the same period the measles studies were led by P.G. Sergiyev also being the director of Y.I. Martsinovsky Institute of Medical Parasitology and Tropical Medicine. O.V. Baroyan was the scientific secretary of the Institute of Virology and later became the director of N.F. Gamaleya Center of Epidemiology and Microbiology.

In the two decades physical and chemical properties of virions and their components in various viruses were studied, the synthesis patterns of viral genomes and proteins coded by them were stablished, the mechanisms of virus penetration into a cell and the ways of conservation of the genetic material of a number of RNA viruses in acute and chronic infections were identified, and the new principles of rational and non-conventional therapy of virus infections. In those years, D.I. Ivanovsky Institute of Virology became the leading virology center of the country dealing with the problems of general and molecular virology and many areas of special virology. The instituted developed methods for obtaining gene engineering tools to be introduced into industrial-scale production.

New vector systems were created (based on bacterial plasmids and animal viruses) as well as new methods for genetic cloning of certain virus genes' information. Not only were bacterial plasmids successfully used as vectors, but also smallpox vaccine viruses, adenoviruses, and herpes viruses. For the first time in the country the particularly genome of the hepatitis B virus and full-size genes of influenza viruses were cloned as well as the genes of some dangerous viruses (Venezuelan, western, and Japanese encephalitis, Lassa and Machupa fever). Cell engineering experiments resulted in creation of cell hybrids producing monoclonal antibodies to structural proteins of many human and animal viruses (hepatitis B, Venezuelan and western encephalomyelitis, tick-borne encephalitis, influenza, and HIV). Based on the genetic structures and the obtained monoclonal antibodies new test systems were developed to identify markers of many human and animal viral infections. The fundamental and application studies results obtained during those 25 years allowed this research center to take the leading positions in the virologic science.

In 1987, D.K. Lvov, a member of the Academy of Medical Sciences of the USSR (later – of the Russian Academy of Medical Sciences, now of the Russian Academy of Sciences), was elected the director of the institute. In the hard years of the perestroika, not only did he manage to retain the institute, but also he established new research divisions and was able to attract young talented specialists. Having been the head of the Institute of Virology for 25 years, D.K. Lvov established and developed the new research areas – molecular ecology and population genetics of viruses focused on studying the role of recombination processes in the mechanisms of forming the gene pool pf virus populations. Using an evolutionary approach and mathematical methods of multifactor analysis, he created a scientifically valid concept of regular patterns of arbovirus circulation in various climatic and geographical belts of the world. He developed a unique method of ecological probing in Russia and the former USSR, which allowed to isolate in the natural focuses more than 60 viruses many of which were registered in the International Catalog of Arboviruses as new to science.

Currently the director of D.I. Ivanovsky Institute of Virology is professor A.V. Pronin. The area of his research interests is related to the problem of immunology of human and animal infectious diseases and in the recent years – to development of new anti-infection immune response modifiers based on polyprenols and germanium organic compounds, studying their action mechanisms and development of the methodology for environmental well-being assessment.

One of the areas of the institute's activities is studies in biological safety and emerging and re-emerging infections able to cause epidemic situations as well as infections caused by viruses with highly changeable genomes. These studies are aimed at identification of epidemic strains of the influenza virus, forecasting and explanation of epizootic and pandemic outbreaks caused by high-pathogenicity types of the influenza A virus (H5N1), and pandemic influenza (H1N1) in Russia. Modern molecular biology, virus genetics, and molecular epidemiology methods are used to analyze the genotypes of influenza virus, hepatitis C virus, HIV, and arboviruses circulating in the country.

The most important event of the recent 25 year is the AIDS epidemy spreading globally. The first strains of the human immunodeficiency virus in the country were isolated by the institute employees. Currently, the institute has a large collection of the strains. Large-scale introduction of molecular genetics methods in epidemiology, resulting from comprehensive efforts of D.I. Ivanovsky Institute of Virology and the Federal AIDS Center as well as practical healthcare workers, made it possible to obtain unique information on the patterns of genetic variability of human immunodeficiency viruses circulating in the country. In cooperation with the specialists from the Institute of Molecular Biology and the Central Epidemiology Institute phosphazide (nikavir), a drug for AIDS/HIV treatment, which is less toxic than azidotimidin, was developed. And, what is especially important, it is much less exposed to drug resistance. The development has been honored with the National Award of the Russian Federation.

Another example of the last decade's studies is exploration of the previously unknown hepatitis C virus, the "silent killer" having more than 10 genotypes each of which shows different pathogenicity. The outcome of the very expensive treatment depends on the virus genotype. D.I. Ivanovsky Institute of Virology has studied propagation of various virus genotypes in the country to establish that the most pathogenic 1b genotype and the 3a genotype are dominating, although different regions have their specifics. This data is used for prescribing the treatment and identification of the prognosis of the disease course. In the course of that work, the previously unknown 2k subtype was characterized. The priority data for development of virus cultivating in laboratory animals and cell cultures have been obtained. Now they are already being used for antivirus drug screening. The development provides great opportunities for obtaining a vaccine against hepatitis C.

The Disease Agent Ecology Center established at the premises of the Institute of Virology has taken the lead in the methodological and organization efforts for exploration of unknown and reemerging infections. Joint efforts of researchers and practitioners the personnel have been taken to train specialists, develop instructions and methodological guidelines, and, what is most important, to ensure proper functioning of the monitoring system for identification of new agents and infections caused by them and analysis of unusual epidemic situations. The theoretical framework for monitoring in various ecosystems using methods of molecular ecology and epidemiology has been developed. The methodological approach provided for probing sites with collection of field materials in the whole territory of Northern Eurasia.

Thus, the ares exceeding 15 million km2 was explored and a potential threat of epidemical situations in various geographical belts was identified. An important role of arboviruses of the California encephalitis complex carried by mosquitos in morbidity of the population in the areas of tundra, taiga, and leafy forests. Summer influenza-like diseases, meningitis, and encephalomeningitis are etiologically connected with this group of viruses. Oil and gas industry workers and miners producing the most important resources of the country are highly exposed to the risk of contamination. Based on the studies' results, the Atlas of Spreading Agents of Natural Nidality Virus Infections in Russia was published. Seven employees of the institute were honored with the National Award of Russia for this work.

Taking into consideration the permanent threat of emergence of new pandemic influenza viruses, virus circulation among people and in the environment in the key point of Northern Eurasia is being monitored. The institute has arranged a quick-response team to deal with emerging epidemiological situations. Establishing such a functional division provided for ability to promptly collect biological material in the infection nidi, quickly identify the agent, isolate and fix the virus in cell cultures, promptly analyze virus sensitivity and/or resistance to drugs, provide a detailed structural and functional characteristic of the virus by whole-genome sequencing and prepare recommendations for the healthcare authorities. All the 15 known influenza viruses were isolated from the collected materials. Perhaps, these very viruses will become the source of new pandemic virus generation, which may emerge at any time. Viruses having caused panic in South East Asia were also isolated from wild birds. The Н5 virus is currently active in the natural biocenoses in Primorye and Altai from which it could be carried to the south of China and possibly – to North America via the Bering Strait by migrating birds. The Institute of Virology has predicted this threat. And forewarned is forearmed. Expert test systems have been prepared for virus diagnostics and isolation and detection and genotyping of the virus DNA. Antiviral activity of the available drugs has been tried. The vaccine strain candidate is being prepared.

In institute immediately got involved in the studies due to the marked aggravation of the epidemical situation in the south of Russia related to the Crimean-Congo hemorrhagic fever and West Nile encephalitis viruses. It is shown that the recent epidemic strains do not differ genetically from those isolated in the same area 40 years ago, which means that the Crimean-Congo hemorrhagic fever epidemic in the south of Russia is not related to any changes in the genetic properties of the virus population.

The phylogenetic analysis of full-size genomes of the epidemic strain of the West Nile fever virus has shown that the Russian epidemic strains are very close to those isolated in America, but are quite different genetically from those isolated in the same region 20–30 years ago when there was no epidemic. Therefore, it has been established that the epidemical situation in the south of Russia in the recent four years is probably conditional upon changes in the genetic properties of the virus population. All the known virus genotypes as well as the fourth genotype previously unknown have been found. The key parameters of the agent ecology and epidemiology have been also identified. The epicenter of the epidemy has been identified. It is located in the middle part of the Volga delta. This is a place of the highest susceptibility of people and domestic and wild animals. Test systems for antibodies and antigen identification and detection of the virus RNA of all the four genotypes.

As it follows from the above, the priority goal of the study is to explore the evolution of viruses able to cause extreme situations providing a threat to the biological safety of the country. To achieve the set goals a wide range of methods is used:

  • methods of clinical epidemiology and zoological parasitology for collection of field material in the epidemic epicenter;
  • virologic, serological, and electronic microscopy methods for isolation of viruses and their identification and diagnostics;
  • methods of molecular genetics (PCR, microchips) for detection of viral nucleic acids;
  • virus genome sequencing for phylogenetic analysis.

The results are used for preparation of modern test systems, development and trial of antivirus drugs, and establishing vaccine strain candidates.

The institute staff proficient in these methods makes a unique team able to meet the challenges arising – first of all, those related to the problem of emerging and reemerging viral infections, being a priority in terms of ensuring biological safety in the country.

Currently, D.I. Ivanovsky Institute of Virology is a division of N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Healthcare of the Russian Federation, according to Order No. 220 of the Ministry of Healthcare of the Russian Federation "On Reorganization of the Federal State Budgetary Institution N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Healthcare of the Russian Federation and the Federal State Budgetary Institution D.I. Ivanovsky Institute of Virology of the Ministry of Healthcare in the Form of Inclusion of the Second Institution in the First One" dd. May 17, 2014.