Vol 63, No 6 (2018)

REVIEWS

THE USE OF MONOCLONAL ANTIBODIES FOR THE TREATMENT OF EBOLA VIRUS DISEASE

Sizikova T.E., Borisevich G.V., Shcheblyakov D.V., Burmistrova D.A., Lebedev V.N.

Abstract

Some drugs candidates for treatment of Ebola virus disease (EVD), have been studied, monoclonal antibody (mAb) cocktails have shown great potential as EVD therapeutics. The advantages of mAb therapy include low toxicity, high specificity and versatility, with the range of biological effects being dependent upon the Fc region. Functions of mAbs include pathogen opsonisation, complement activation, antibody-dependent cell cytotoxicity and virus neutralization characteristics. The most known mAb cocktail, used as therapeutic, is ZMapр, manufactured by «Leaf Biopharmaceutical» from 2004. The elaborated mAb cocktails, structures and properties s of mAbs, the protective characteristics of mAbs and development of new pan-ebolavirus mAbs are reviewed in this article.

Problems of Virology. 2018;63(6):245-249
pages 245-249 views

MODERN ETHIOTROPIC CHEMOTHERAPY OF HUMAN CYTOMEGALOVIRUS INFECTION: CLINICAL EFFECTIVENESS, MOLECULAR MECHANISM OF ACTION, DRUG RESISTANCE, NEW TRENDS AND PROSPECTS. PART 2

Andronova V.L.

Abstract

A number of synthetic compounds, such as the nucleoside analog ganciclovir, its L-valine ester (a metabolic precursor of ganciclovir) and pyrophosphate analog foscarnet, are permitted for the treatment of HCMV-related diseases in the WHO European Region. The viral DNA- polymerase is used by all these drugs as a bio-target. However, the usage of standard anti-CMV therapy is accompanied by severe side effects, as well as the development of drug resistance in the virus, mainly in conditions of immunodeficiency. In this review, we focused on viral proteins of interest as new potential targets and their inhibitors, such as the inhibitor of human CMV terminology, lethermovir, which showed great activity in the third phase of clinical trials, inhibitors of viral cyclin-dependent kinase (maribavir, cyclopropavir ) and a number of compounds exhibiting anti-HCMV-activity, undergoing only preclinical trials in the experiment. Inclusion of new anti-CMV agents that are active against GСV/PFA/CDV-resistant strains of CMV into standard prophylactic and therapeutic regimens, will allow to increase the effectiveness of anti-CMV therapy, including in cases when standard therapy is ineffective. Areas covered: the international databases such as A MEDLINE, PubMed, eLIBRARY.RU, ClinicalTrials.gov., etc. with the purpose of obtaining information on compounds showing selective action against the human cytomegalovirus, the most promising for the development of drugs.

Problems of Virology. 2018;63(6):250-260
pages 250-260 views

ORIGINAL RESEARCH

MESENCHYMAL STEM CELLS ENHANCE IMMUNE RESPONSE AND PROTECTMICE AGAINST LETHAL HERPES VIRAL INFECTION

Klimova R.R., Momotyuk E.D., Demidova N.A., Yarigina E.I., Kushch A.A.

Abstract

The objective of this study was to evaluate immunoregulatory and protective potential of mesenchymal stem cells (MSC) in a mouse model of lethal HSV1 infection. MSC were isolated from bone marrow of DBA mice and cultured in flasks with DMEM containing 10% FBS, insulin, transferrin, selenite, fibroblast growth factor, glutaminе and gentamicin. Antiviral activity was tested on HSV1-infected Vero cells. In vivo experiments were performed on DBA mice divided into 5 groups (10 animals each): group 1, intact (naïve) mice; group 2, intravenous (iv) MSC injection; group 3, intraperitoneal infection with 20 LD50 HSV1 followed by MSC injection; group 4, HSV1 infection followed by acyclovir (ACV) injection; group 5, HSV1 infection and iv injection of saline. Isolated cells were consistent with MSC morphologically, by adhesive ability and surface receptors. Conditioned media from MSC collected after 4-5 passages inhibited HSV1 infection in vitro by 64-70% and contained IL-6 and TNF-α, whose concentrations were 5- and 20-fold higher, respectively, than in the control. MSC and ACV injections protected 70% and 60% of DBA mice, respectively, compared with the control (group 5, 10% survival). High activity of virus neutralizing anti-HSV1 antibodies and activation of T cell proliferation were observed in survived mice from group 3. Serum levels of IL-6 and TNF-α in these mice were lower and that of INF-γ much higher than in agonizing animals of this group (Р<0.05). These findings indicate that MSC therapy is a prospective approach to the development of new effective management of generalized HSV1 infection.

Problems of Virology. 2018;63(6):261-267
pages 261-267 views

ISOLATION AND PHYLOGENETIC ANALYSIS OF FELINE CALICIVIRUS IN SIBERIA

Glotova T.I., Semenova O.V., Nikonova A.A., Glotov A.G., Vyatkin Y.V., Bondar A.A.

Abstract

The results of the study of the distribution of calicivirus infection in a population of domestic cats of different breeds, contained individually or the group method, the virus isolation in the cell culture and a comparative phylogenetic analysis of their nucleotide sequences with published sequences of reference field and vaccine strains of Feline calicivirus (FCV) from other countries: USA, Germany, Japan, China and Korea are presented. Clinical signs of infection were found in 14.3% of the animals examined. After several passages in the primary kidney cells of the kitten embryo, seven cytopathogenic isolates FCV were isolated: 1 - from a cat with an acute infection, 5 - subclinical infection, 1 - systemic infection. They were adapted to continuous FK-81 cells in which they reached a maximum infectious activity of 10.0 ± 1.15 lg TCD 50 / cm3. Based on the sequence analysis of the open reading frame 2 region of the viral genome Eshli strain showed a close relationship with strain KM016908 from China with the identity of the nucleotide sequences between them of 81.0%. The results of the investigations showed that FCV isolates obtained from animals on the territory of Siberia are genetically different from strains included to imported vaccines used to prevent disease in Russian Federation and also among themselves. This causes a decrease in the effectiveness of preventive measures. In nurseries that do not have contacts and connections between themselves but located in the same geographic region FCV populations may have some genetic differences. A close relationship of some field isolates with strains from other countries geographically located so far from the Siberian region has been revealed. Studies on the molecular epizootology of caliciviruses are important in the development of test systems and the monitoring of the spread of strains in Russia.

Problems of Virology. 2018;63(6):268-274
pages 268-274 views

MONOCLONAL ANTIBODIES TO HEMAGGLUTININ OF INFLUENZA B VIRUSES VICTORIA EVOLUTIONARY LINEAGE

Sorokin E.V., Tsareva T.R., Zheltukhina A.I.

Abstract

Co-circulation of two evolutionary distinct lineages of influenza virus in one epidemic season has led to development specific reagents for rapid identification and typing of new isolates. Panel of MAbs to hemagglutinin of influenza virus B/Brisbane/46/15 belonging to Victoria evolutionary lineage was developed. All MAbs reacted in ELISA with B/Victoria-like strains only. There were no interactions with heterologous influenza viruses of B/Yamagata lineage, seasonal and potentially pandemic influenza A viruses. All MAbs reacted in hemagglutination inhibition and virus neutralization. MAbs interacted in hemagglutination inhibition only with B/Victoria-like viruses, but did not interacted B/Yamagata-like strains. Neutralization and hemagglutination inhibition studies of viruses isolated before 1983 with MAbs revealed that MAbs 6E11, 9G5, 9B5 and 6A4 had the ability to interact with the virus B/ Russia/69 which may evidence that B strains of early isolation period (before lineage separation) have common epitope with recent Victoria lineage viruses. MAbs 7C8, 7G9, 7H8 and 8D11 were directed to a conserved epitope (or epitopes) specific for influenza hemagglutinin viruses of B/Victoria group. The presence of differences in the effectiveness of the interaction of MAbs 6A9, 7G9 and 8A8 in hemagglutination inhibition test allows the identification and differentiation of strains isolated in chicken embryos and MDCK cell culture. Thus, the developed MAbs can be successfully used for identification and antigenic analysis of B/Victoria-like strains.

Problems of Virology. 2018;63(6):275-280
pages 275-280 views

ANNIVERSARY DATES

M.A. SELIMOV: CONTRIBUTION TO THE DEVELOPMENT OF ISSUES OF PREVENTION OF RABIES, PERSONALITY AS A SCIENTIST AND PERSON (ON THE 100TH ANNIVERSARY OF THE BIRTH, 1918-2001)

Botvinkin A.D., Mikhailovsky E.M.

Abstract

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Problems of Virology. 2018;63(6):281-284
pages 281-284 views

IN MEMORY OF PROFESSOR NIKOLAY PETROVICH MAZURENKO (1919-1984)

Gurtsevich V.E., Mazurenko N.N.

Abstract

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Problems of Virology. 2018;63(6):285-287
pages 285-287 views


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