Vol 63, No 4 (2018)

REVIEWS

MODERN ETHIOTROPIC CHEMOTHERAPY OF HERPESVIRUS INFECTIONS: ADVANCES, NEW TRENDS AND PERSPECTIVES. ALPHAHERPESVIRUSES (PART II)

Andronova V.L.

Abstract

A key role in the treatment of herpesviral infections is played by modified nucleosides and their predecessors - acyclovir, its L-valine ester (valaciclovir) and famciclovir (prodrug of penciclovir). The biological activity of compounds of this class is determined by their similarity to natural nucleosides. After phosphorylation by viral thymidine kinase and then cell enzymes to the triphosphate forms, acyclovir and penciclovir inhibit the activity of viral DNA polymerase and synthesis of viral DNA. The increasing role of herpesvirus infections in human infectious pathology, as well as the development of drug resistance in viruses, mainly in patients with immunodeficiencies of various origins, necessitate the search for new compounds possessing anti-herpesvirus activity, using as a biological target not DNA polymerase, but other viral proteins and enzymes, unique or different from cellular proteins, performing similar functions.
Problems of Virology. 2018;63(4):149-159
pages 149-159 views

PROBLEMS OF ISOLATION, IDENTIFICATION AND ANTIGENIC CHARACTERIZATION OF RECENT HUMAN A(H3N2) INFLUENZA VIRUSES

Petrova P.A., Konovalova N.I., Danilenko D.M., Vasilieva A.D., Eropkin M.Y.

Abstract

Human A (H3N2) influenza viruses are distinguished by a high rate of evolution and regularly cause epidemics around the world. Their ability to adapt and to escape from the host's immune response and to change their receptor specificity is very high. Over the past 20 years, these viruses have lost the ability to agglutinate red blood cells of chickens and turkeys and have practically ceased to propagate in chicken embryos - the main source of influenza vaccines. Isolation of viruses in the MDCK cell culture led to the selection of strains that lose one of the potential glycosylation sites. Many of the A (H3N2) strains have acquired mutations in neuraminidase, which distort the results of antigenic analysis in the hemagglutination inhibition test - the cornerstone method for the analysis of the match between viral isolates circulating in human population to strains selected for the influenza vaccines. In this regard, the characteristics of the antigenic properties of influenza A (H3N2) viruses by traditional methods become poorly informative, and the selection of vaccine strains of this subtype is erroneous, which is reflected in the discrepancy between vaccine and circulating A (H3N2) viruses in recent years (2013-2014, 2014 -2015, 2015-2016). The search, development and implementation of new algorithms for the isolation and antigen analysis of influenza A (H3N2) viruses are extremely urgent.
Problems of Virology. 2018;63(4):160-164
pages 160-164 views

ORIGINAL RESEARCH

INCREASED FORMATION OF PHOSPHORYLATED H2AX FOCI IN NUCLEI OF CELLS INFECTED BY HEPATITIS B AND B+D VIRUSES

Kostyushev D.S., Brezgin S.A., Kostyusheva A.P., Lipatnikov A.D., Simirskii V.N., Mamonova N.A., Volchkova E.V., Maleyev V.V., Chulanov V.P.

Abstract

Liver cirrhosis and hepatocellular carcinoma are the most common outcomes of chronic hepatitis B. Hepatitis B virus (HBV) induces transformation and cell death in chronic hepatitis B (CHB). DNA double strand breaks (DSBs) represent the most dangerous type of genome damage. It was shown previously that generation of phosphorylated histone H2AX foci is a reliable marker of DSBs. The aim of this study was to analyse generation of yH2AX foci in HBV and hepatitis D virus (HDV) infection in vitro and in liver biopsies of patients with CHB and CHB with delta-agent (CHD). Human hepatoma cell line HepG2-1.1merHBV with activated HBV life cycle was used to perform real-time PCR for analysis of pregenomic RNA, HBV DNA, HBV cccDNA and for immunocytochemical analysis of yH2AX. Liver biopsies from CHB and CHD patients were analyzed to confirm the results. HBV induces multiple discrete yH2AX foci in HepG2-1.1merHBV cells in vitro and in biopsies of CHB and CHB+D patients. The ratio of hepatocytes w/o yH2AX foci is significantly lower (49,9+/-12,3% vs. 85,5+/-0,9%, p<0,05), while the proportion of cells with 1-10 yH2AX foci is higher (49,3+/-12,6% vs. 14,5+/-0,9%, p<0,05) compared to healthy control. There is a significant increase in the mean number of yH2AX foci in biopsies from CHB+D patients (3,5+/-1,1 and 5,5+/-1,5 vs. 0,5+/-0,16 in control hepatocytes, p<0.05). The ratio of hepatocytes w/o yH2AX foci is significantly lower in CHB and CHB+D patients, while percentage of cells with 1-10 yH2AX foci is higher. Rare hepatocytes with multiple (11-30 yH2AX foci per cell) foci appear in CHB and CHB+D patients. In conclusion, yH2AX foci are generated in hepatocytes of CHB and CHB+D patients and can be utilized to assess genome damage, associated with HBV and HDV viral infection.
Problems of Virology. 2018;63(4):165-170
pages 165-170 views

COMPARATIVE ANALYSIS OF SEROLOGICAL MARKERS OF HERPES VIRUSES AND QUANTITATIVE IMMUNOGLOBULINOPATHIES IN PRIMARY PATIENTS WITH ANGIOIMMUNOBLASTIC T-CELL LYMPHOMA

Chernova N.G., Tihomirov D.S., Soboleva N.P., Mariina S.A., Sidorova Y.V., Sinitsyna M.N., Dvirnyk V.N., Kulikov S.M., Tupoleva T.A., Zvonkov E.E.

Abstract

Introduction. Angioimmunoblastic T-cell lymphoma (AITL) is associated with the Epstein-Barr virus (EBV) in most cases. It is believed polyclonal hypergammaglobulinaemia observed in 53-80% of AITL patients has anti-herpes viral antibodies as its substrate. Aim. The aim of the study was to compare serological markers of herpes viruses and quantitative immunoglobulinopathies of classes M and G in primary patients with AITL. Materials and methods. 26 primary patients with newly diagnosed AITL treated at the National Research Center for Hematology from 2002 to 2017 were enrolled in the study. The male/female ratio was 16/10; median age was 62 (29-81) years. The levels of total immunoglobulins of classes M and G, serological markers of EBV, cytomegalovirus (CMV) and herpes simplex virus type 1 and type 2 (HSV 1, 2) were assessed in all patients. Results. Significant relationship was found between the presence of virus-specific IgM (IgM HSV 1, 2, IgM CMV, IgM VCA EBV) and an elevated level of total immunoglobulins of class M (p <0.0001). Studies of each virus separately showed that the greatest correlation was observed for IgM HSV 1, 2 (p <0,0001), whereas the association of IgM CMV and IgM VCA EBV with quantitative immunoglobulinopathies of class M was not confirmed (p = 0,15 and p = 0,36 respectively). There was no considerable relationship between polyclonal IgG hypergammaglobulinaemia and an increased level of antiviral IgG (IgG HSV 1, 2, IgG CMV, IgG EBNA-1 EBV, IgG EA EBV) (p> 0,37). Conclusion. We have shown that the presence of the anti-herpes viral IgM strictly correlates with polyclonal IgM hypergammaglobulinaemia, while an increased level of virus-specific IgG antibodies does not affect the formation of polyclonal IgG hypergammaglobulinaemia and can be observed in IgG hypogammaglobulinaemia.
Problems of Virology. 2018;63(4):171-176
pages 171-176 views

FEATURES OF EPIDEMIC PROCESS OF INFLUENZA A(H1N1)PDM09 AND A(H3N2) IN RUSSIA FROM 2009 TO 2017

Karpova L.S., Volik K.M., Stolyarov K.A., Popovtseva N.M., Stolyarova T.P., Sominina A.A., Burtseva E.I.

Abstract

The goal of this work is to compare the key parameters of influenza epidemics of different etiology. Four epidemics of influenza with predominance of influenza A(H1N1)pdm09 and 4 epidemics of influenza A(H3N2) were analyzed using the database of the Federal State Research Institute of Influenza on morbidity, hospitalization, deaths from influenza in 59 cities in the period from 2009 to 2017. The intensity of epidemics involving the influenza A(H1N1)pdm09 decreased from high to medium, while the intensity of epidemics of influenza A(H3N2) increased from low to medium. In the epidemic of influenza A(H1N1)pdm09 in the total population, the incidence of influenza and ARI decreased by a factor of 1.6, while the mortality among patients decreased by a factor of 1.7 in all age groups, except for those over 65 years, for whom the incidence and mortality increased by factors of 1.4 of 2.3, respectively. In the epidemic of A(H3N2), a trend for increasing morbidity and mortality was more pronounced among individuals older than 65 years. Pandemic influenza remains the leading cause of deaths. Among the dead in the epidemic of influenza A(H1N1)pdm09, the proportion of young individuals decreased (including a fourfold decrease of lethality in pregnant women), while the proportion of persons over 65 years increased 7.8 times; in the epidemic of influenza A(H3N2) only 2.5-fold increase was observed. In the epidemic of influenza A(H1N1)pdm09, the proportion of lethality increased among people with cardiovascular diseases and diseases of the internal organs; in the epidemic of influenza A(H3N2), the proportion of lethality increased among people with immunodeficiency, diseases of the internal organs and respiratory system.
Problems of Virology. 2018;63(4):177-184
pages 177-184 views

PHYLOGENETIC ANALYSIS OF BOVINE PESTIVIRUSES DETECTED IN SIBERIA

Glotov A.G., Koteneva S.V., Glotova T.I., Yuzhakov A.G., Maksyutov R.A., Zaberezhnyy A.D.

Abstract

The results of phylogenetic analysis of three species of bovine pestiviruses circulating in six regions of Siberia, as well as those detected in fetal embryonic serum (FBS) and continuous cell cultures, are presented. The typing was made based on comparison of sequences from the 5' untranslated region (5'-UTR) of the viral genome. Among the highly productive dairy cattle, circulation of five subtypes of the BVDV1 (a, b, d, f, r) and BVDV2 was established. The predominant subtype was 1b (48% positive samples). The number of subtypes of BVDV1 was as follows: BVDV1: 1а (8%), 1b (48%), 1d (8%), 1f (16%) и 1r (8%) and BVDV2 (12%). Cell cultures revealed BVDV1a. The distribution of types and subtypes of viruses had geographical differences. BVDV1b, BVDV1d, BVDV1f и BVDV1r were detected in cattle or persistently infected (PI) animals in farms with respiratory distress. BVDV 1a revealed in the serum of PI heifer without manifestation of clinical symptoms. BVDV2 were detected in cattle with pathology of reproduction. The presence of the BVDV3 (atypical pestivirus) of the Italian group was established in seven lots of FBS obtained from two manufacturers. No evidence has been found for circulating of the atypical virus among cattle of various breeds, including imported, reindeers and red deers. Studies on the molecular epizootology of pestiviruses can be used to select and optimize the control strategy and address the issue of vaccine use in a particular region.
Problems of Virology. 2018;63(4):185-191
pages 185-191 views


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