FEATURES OF EPISOTIC PROCESS AND MOLECULAR-GENETIC CHARACTERISTICS OF VIRUS ISOLATES OF RABIES IN TVER REGION.

Rabies epidemic situation in the Tver Region has been studied. Animals of different species that had confirmed clinical rabies were statistically analyzed. It was established that the features of the course of epizootics in the Tver region correspond to the regularities characteristic of rabies of the natural-focal type.

Taxonomy of the family Arenaviridae and the order Bunyavirales: update 2018.

In 2018, the family Arenaviridae was expanded by inclusion of 1 new genus and 5 novel species. At the same time, the recently established order Bunyavirales was expanded by 3 species. This article presents the updated taxonomy of the family Arenaviridae and the order Bunyavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and summarizes additional taxonomic proposals that may affect the order in the near future.

DRIFT OF INFLUENA A(H3N2) VIRUS: BIOLOGICAL, ANTIGENIC AND GENETIC PROPERTIES IN EPIDEMIC SEASON 2016-2017 IN RUSSIA AND COUNTRIES OF THE NOTHERN HEMYSPHERE.

The article presents the features of the influenza virus circulation for the period from October 2016 to May 2017 in some territories of Russia collaborating with the D.I. Ivanovsky Institute of Virology, Federal State Budgetary Institution "N.

State of the Art in HIV Drug Resistance: Science and Technology Knowledge Gap.

Resistance to antiretroviral therapy (ART) threatens the efficacy of human immunodeficiency virus type 1 (HIV-1) treatment. We present a review of knowledge gaps in the science and technologies of acquired HIV-1 drug resistance (HIVDR) in an effort to facilitate research, scientific exchange, and progress in clinical management. The expert authorship of this review convened to identify data gaps that exist in the field of HIVDR and discuss their clinical implications.

State of the Art in HIV Drug Resistance: Surveillance and Regional Gaps.

This article is the second of a two-part review aiming to identify gaps in the knowledge and management of human immunodeficiency virus type 1 drug resistance (HIVDR) from global and regional perspectives. Here, we examine the policy and programmatic gaps in HIVDR surveillance, the affected populations and settings, and implications for clinical practice. The expert authorship of this review convened to identify gaps in HIVDR surveillance, with a particular focus on specific regional variations within and between Europe and Asia, to highlight directions for research and implementation.

DNA sequence-specific ligands. XVII. Synthesis, spectral properties, virological and biochemical studies of fluorescent dimeric bisbenzimidazoles DBA(n).

A series of DNA minor groove binding fluorescent dimeric bisbenzimidazoles DBA(n) bearing linkers of various length were synthesized and their biochemical and antiviral activities were evaluated. Their antiviral activity was assessed in model cell systems infected with human herpes simplex virus (HSV-1) and cytomegalovirus (CMV). Compounds DBA(1) and DBA(7) demonstrated in vitro inhibitory properties towards HSV-1, and DBA(7) completely blocked the viral infection.

Tick-borne encephalitis virus in arthropod vectors in the Far East of Russia.

Isolates of tick-borne encephalitis virus (TBEV) from arthropod vectors (ticks and mosquitoes) in the Amur, the Jewish Autonomous and the Sakhalin regions as well as on the Khabarovsk territory of the Far East of Russia were studied. Different proportions of four main tick species of the family Ixodidae: Ixodes persulcatus P. Schulze, 1930; Haemaphysalis concinna Koch, 1844; Haemaphysalis japonica douglasi Nuttall et Warburton, 1915 and Dermacentor silvarum Olenev, 1932 were found in forests and near settlements.

Spatiotemporal Characteristics of the HIV-1 CRF02_AG/CRF63_02A1 Epidemic in Russia and Central Asia.

Eastern European countries, including Russia, Ukraine, and other former Soviet Union (FSU) countries, have experienced a human immunodeficiency virus (HIV) epidemic spreading mostly among people who inject drugs (PWID). We aimed to investigate the origin and the dispersal patterns of HIV-1 CRF02_AG in Russia and other FSU countries. We studied 136 CRF02_AG sequences originating from Russia, and FSU countries along with a globally sampled dataset of 3,580 CRF02_AG sequences.

[Requirements for the Induction of Broadly Neutralizing Antibodies against HIV-1 by Vaccination].

A study of the induction of broadly neutralizing antibodies (bNAbs) in HIV-infected patients and vaccinated subjects revealed the main criteria for the formation of bNAbs (the duration of exposure to a viral antigen, the effect of the diversity of HIV variants, and the removal of barriers associated with the Env-dependent defense mechanisms of HIV-1). Modified trimers of the HIV-1 envelope protein (Env) exposed on virus-like particles (VLP) have unique properties: they (i) modulate the exposure of binding sites (bs) of the CD4 receptor and co-receptor; (ii) create steric restrictions for contact with bNAbs; (iii) increase the Env presentation density, thus enhancing the immune response; (iv) form stable trimers that do not induce off-target immune responses; and (v) allow additional modifications to their structure and construction of a platform with immunostimulating molecules. Immunization using a heterologous subtype-cross prime-boost regime with modified trimeric Env is capable of inducing somatic hypermutation levels necessary for the formation of bNAbs.

[Next-Generation Techniques for Discovering Human Monoclonal Antibodies].

Monoclonal antibodies have found wide applications in the treatment of cancer, as well as of autoimmune, infectious, and other diseases. Several dozen new antibodies are currently undergoing different stages of clinical trials, and some of them will soon be added to the list of immunotherapeutic drugs. Most of these antibodies have been generated using hybridoma technology or a phage display.

[Molecular epidemiological analysis of HIV-1 variants circulating in Russia in 1987-2015].

Aim: To simultaneously analyze HIV-1 samples from all Russian regions to characterize the epidemiology of HIV infection in the country as a whole.

Subjects And Methods: The most extensive study was conducted to examine nucleotide sequences of the pol gene of HIV-1 samples isolated from HIV-positive persons in different regions of Russia, with the diagnosis date being fixed during 1987-2015. The nucleotide sequences of the HIV-1 genome were analyzed using computer programs and on-line applications to identify a virus subtype and new recombinant forms.

Genetic characterization of bank vole virus (BaVV), a new paramyxovirus isolated from kidneys of bank voles in Russia.

A genome of bank vole virus (BaVV), isolated from kidney tissues of bank voles (Myodes glareolus) in Russia in 1973, was sequenced. The genomic organization of BaVV (3'-N-P/V/C-M-F-G-L-5', 16,992 nt in length; GenBank accession number MF943130) is most similar to that of Mossman virus (MoV) and Nariva virus (NarPV), two ungrouped paramyxoviruses isolated from rodents in Australia and Trinidad, respectively. The proteins of BaVV have the highest level of sequence identity (ranging from 23-28% for G protein to 66-73% for M protein) to proteins of MoV and NarPV.

Isolation and genetic characterization of encephalomyocarditis virus 1 from a deceased captive hamadryas baboon.

In 2007, numerous hamadryas baboons (Papio hamadryas) died suddenly in an aviary of a primate institute in Sochi, Russia, in the absence of prior clinical signs. Necropsies were suggestive of encephalomyocarditis virus infection, but RT-PCR assays with commonly used primers were negative. Here we report the histopathological results obtained during necropsies and the isolation and genomic characterization of a divergent strain of encephalomyocarditis virus 1 (EMCV-1) from heart tissue of one of the succumbed hamadryas baboons.

Modulation of Cell Death Pathways by Hepatitis C Virus Proteins in Huh7.5 Hepatoma Cells.

The hepatitis C virus (HCV) causes chronic liver disease leading to fibrosis, cirrhosis, and hepatocellular carcinoma. HCV infection triggers various types of cell death which contribute to hepatitis C pathogenesis. However, much is still unknown about the impact of viral proteins on them.

INFLUENCE OF IMMUNOMODULATORY DRUG STIMFORTE ON THE EXPERIMENTAL HERPES VIRUS INFECTION IN COMBINATION WITH ACYCLOVIR AND ON HIV-INFECTION IN COMBINATION WITH RETROVIR.

The combined action of the immunostimulatory drug Stimforte and the basic etiotropic drug acyclovir commonly used to treat herpes infections was studied using the model of lethal experimental infection of mice BALB/c with herpes simplex virus type 1. It was found that the interaction of these drugs is additive. In addition, Stimforte inhibits infection caused by a strain of virus, which is highly resistant to acyclovir.

Biochemical Variations in Cytolytic Activity of Ortho- and Paramyxoviruses in Human Lung Tumor Cell Culture.

Human lung cancer cells (Calu-3 line) were studied for the development of apoptosis, necrosis, and autophagy in response to infection with ortho- and paramyxoviruses. Biochemical pathways underlying various mechanisms of cell death differed for different viruses. When infected with murine Sendai paramyxovirus, Calu-3 cells demonstrated typical necrotic features such as cell swelling (but not shrinkage), lack of chromatin DNA laddering, of caspase 3 and 8 activation, and of apoptotic cleavage of poly(ADP-ribose) polymerase (PARP) protein; an activation of antiapoptotic protein kinase Akt was also revealed.

Complete Genome Coding Sequences of Artashat, Burana, Caspiy, Chim, Geran, Tamdy, and Uzun-Agach Viruses (: : ).

The bunyaviral monogeneric family currently includes 12 species for 35 distinct viruses. Here, we present the complete genome coding sequences of an additional seven nairoviruses. Five of them can be assigned to established species, whereas two of them (Artashat and Chim viruses) ought to be assigned to two novel species.

Regional Challenges in the Prevention of Human Immunodeficiency Virus Drug Resistance.

In diverse global regions with significant human immunodeficiency virus (HIV) burden, programmatic, cultural, and provider-, patient-, and virus-related factors may result in HIV drug resistance, with global implications. This article reviews such common and unique challenges in Russia, Latin America and the Caribbean, China, and India, to suggest potential solutions.

HIV Type 1 Integrase Natural Polymorphisms in Viral Variants Circulating in FSU Countries.

Background: Natural variability of integrase (IN) across HIV-1 variants may influence the emergence of resistant viruses. The most apparent explanation of this fact is the IN polymorphism and the associated differences in codon usage, which in turn, influence the probability and the terms of DRMs acquisition. Possible mechanisms by which polymorphisms affect DRMs emergence remain disputed and should still be clarified because these substitutions may be associated with a reduced activity of some INSTIs and may impact on ART regimen choice depending of HIV-1 subtype.

Cycluridine: A novel antiviral effective against flaviviruses.

This review describes the contemporary state of research for antivirals effective against flaviviruses, especially focusing on inhibitors of the pestivirus causative agent of bovine viral diarrhoea virus. We highlight cycluridine, an originally synthesized Mannich's base [a tetrahydro-2(1H)-pyrimidinones derivative], as a highly effective antiviral possessing a strong inhibitory effect on bovine viral diarrhoea virus replication. Cycluridine was active against replication of a wide variety of bovine viral diarrhoea virus strains in cell cultures.

[Low-molecular-weight regulators of biogenic polyamine metabolism affect cytokine production and expression of hepatitis С virus proteins in Huh7.5 human hepatocarcinoma cells].

Hepatitis C virus (HCV) induces the expression of the genes of proinflammatory cytokines, the excessive production of which may cause cell death, and contribute to development of liver fibrosis and hepatocarcinoma. The relationship between cytokine production and metabolic disorders in HCV-infected cells remains obscure. The levels of biogenic polyamines, spermine, spermidine, and their precursor putrescine, may be a potential regulator of these processes.

DIAGNOSTIC CAPACITY OF DETECTION OF SPECIFIC ANTIBODIES TO PANDEMIC INFLUENZA A(H1N1)PDM09 VIRUS.

Serologic studies occupy a significant place in influenza diagnosis. The article presents an analysis of the developed experimental version of ELISA test-systems for the detection of specific antibodies to the virus influenza A(H1N1)pdm09, and their dynamics at different stages of infection as compared with those of the traditional HAI method. The study included 20 paired samples of serum from patients hospitalized at different stages of the disease with etiology associated with the influenza virus A(H1N1)pdm09.

MOLECULAR-GENETIC CHARACTERIZATION OF FIELD ISOLATES OF RABIES VIRUS IDENTIFIED IN THE TERRITORY OF VLADIMIR, MOSCOW, TVER, NIZHNY NOVGOROD AND RYAZAN REGIONS.

The article presents a molecular genetic study of genomes of field isolates of rabies virus isolated in the Vladimir, Moscow, Tver, Nizhny Novgorod and Ryazan regions, with the aim of carrying out phylogenetic analysis. We studied 20 samples of purified PCR products containing the rabies virus nucleoprotein. The samples were provided by the Vladimir veterinary service.

Genetic Variants of HIV Type 1 in Men Who Have Sex with Men in Russia.

The men who have sex with men (MSM) population infected with HIV is poorly studied in Russia because of stigma and discrimination. In the first years of the HIV epidemic, the only HIV genetic variant that circulated among MSM was subtype B, usually acquired abroad. Meanwhile, the massive epidemic of HIV in Russia was caused by a highly homogenic subtype A variant, A (A6), and spread mainly among drug users.

New modified 2-aminobenzimidazole nucleosides: Synthesis and evaluation of their activity against herpes simplex virus type 1.

Using the enzymatic transglycosylation reaction β-d-ribo- and 2'-deoxyribofuranosides of 2-amino-5,6-difluorobenzimidazole nucleosides have been synthesized. 2-Amino-5,6-difluoro-benzimidazole riboside proved to exhibit a selective antiviral activity (selectivity index >32) against a wild strain of the herpes simplex virus type 1, as well as towards virus strains that are resistant to acyclovir, cidofovir, and foscarnet. We believe that this compound might be used for treatment of herpes infections in those cases, when acyclovir is not efficient.