Virus Ecology Department

Managed by RAS academician D.K. Lvov.

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.

LvovPutin

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.

Elena Ivanovna Burtseva
Aleksey Lvovich Belyayev

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.

Alexey Gennadievich Prilipov