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Biomedical subjects

A G Bukrinskaia

Publications and source records attributed to A G Bukrinskaia.

At least 19 recordsLinked to original sources

[Assembly and maturation of HIV-1--targets for new anti-HIV compounds].

Much progress has been recently made in research of the final stages of the HIV-1 life cycle, i.e. of its assembly, gemmation and maturation. The virus was shown, in particular, to use widely cell mechanisms in its replication and assembly. The TSG 101 cellular endosomal sorting protein interacting with the p6 viral protein is necessary for gemmation. Cyclophilin and HP68 (cell proteins) needed for marphogenesis of the virus were identified. The recently obtained data on the interaction of Vif (a viral protein) and Apobec (a cell protein) showed that HIV-1 has an action mechanism overcoming the cell barriers. The "early" virus phenomenon, which is deprived of any mature structure or the ability to infect and does not contain mature Gag and Env proteins, illustrates that the proteolytic pressing of the Gag p55 precursor is not enough for the maturation of the virus and additional viral or cellular factors are needed for the virus to become infectious. Although the current antiviral therapy has been successful enough, it is far from being effective in all cases; one of the reasons is resistance to chemodrugs developing rapidly in patients. Fast mutations and exceptional plasticity of the viral genome (which helps the virus to develop rapidly resistance to drugs) belong to the major problems. The circulation of persistent virus variants has been quickly increasing. There is an urgent need in developing new antiviral drugs acting on new viral targets; progress in experimental virology would speed it up. Thus, new drugs can be created, which block the activity of Vif, that would make Apobec block the virus replication. Compounds can be developed, which block the interaction of cyclophilin and TSG101 with viral proteins. The recently described importance of cholesterol in the sexual transfer of viruses is expected to bring simple and inexpensive compounds destroying cholesterol in the mucous tunic of genitals into clinical use. The identification of additional factors needed for the maturation of the virus and for its becoming infectious can be a basis for the development of drugs blocking their packaging into virions. Future research is expected to define new targets for the chemotherapy of AIDS and to promote the designing of new chemodrugs.

APOBEC-1 Deaminase↗

[Effect of the membrane potential on the fusion of the Sendai viral envelope with the membrane of chick erythrocytes and on virus-induced erythrocyte hemolysis].

The ESR data on the influence of membrane potential of the fusion of Sendai virus envelope with erythrocyte membrane are presented. The hyperpolarization of cell membrane takes place at low concentration of KCl (1-5 mM) in extracellular medium in the presence of valinomycin, while at high concentration of KCl (125-150 mM) its depolarization occurs. The hyperpolarization of erythrocyte plasma membrane is accompanied by the increase of its fusion with viral envelope and virus-induced hemolysis. At the same time depolarization of erythrocyte membrane leads to the decrease of virus fusion activity. This evidence together with previously obtained by patch-clamp method data on potential-dependence of virus-induced increase of cell membrane conductivity provide us an opportunity to make a proposal that the electric field membrane damage may be the initial stage of the virus-induced membrane fusion.

Animals↗

[Rotaviruses: structural and functional organization of the virion].

The data on the structural and functional organization of human rotaviral virion and rotaviral virions of different species of animals obtained by the native and foreign researchers for the last five years of study have been summarized. The virion ultrastructure, the genomic structure and polypeptide composition of rotaviruses are discussed. The data are presented on the transcription and molecular mapping of rotaviral genome. Special attention is paid to localization of rotaviral proteins in the virion capsid, to their function and derivation. The data on the role of endogenous enzymes in rotaviral transcription and replication are presented separately.

Genes, Viral↗

[Antiviral activity of proteinase inhibitors in cultured cells infected with alpha-viruses].

The ability of synthetic inhibitors of trypsin-like (TLCK) and chymotrypsin-like (TPCK) proteinases and natural antiproteinase oligopeptides of animal (aprotinin) and microbial (enzistatin) origin to suppress multicycle replication of different alpha viruses (Semliki, Sindbis, Venezuelan equine encephalomyelitis viruses) in cultured cells was studied. Antiviral activity was found to be induced by TPCK and aprotinin (Gordox). These compounds were shown to reduce virus yield 100-fold and to prevent the involvement of cells into infection process. The mechanisms of antiviral activity and chemotherapeutic possibilities of antiproteinase compounds are discussed.

Alphavirus↗

[Identification of monoclonal antibodies against protein E1 of venezuelan equine encephalomyelitis virus blocking the hemagglutinating but not the infective activity of virions].

Cellular clone (MAK 14-7), producing antibodies against the virus of Venezuela equine encephalomyelitis (VEE), strain 230, was isolated using the standard hybridomata technology. Monoclonal antibodies neutralized the viral hemagglutinating activity leaving the infectious one intact. Monoclonal antibodies from MAD 14-7 reacted specifically with viral glycoprotein E1 as registered by the immunoprecipitation technique. The topography of antigenic determinants of viral E1/E2 glycoprotein dimer forming the virions outer spikes is discussed in connection with the results obtained.

Animals↗

[Analysis of the antigenic and immunogenic properties of protein M of the influenza virus by an immunoenzyme method].

A test system permitting the detection of influenza virus protein M at a concentration of 0.1-0.5 ng/ml in ELISA has been developed. The use of this system made it possible to detect influenza viruses A and B directly in crude virus-containing material and clinical samples obtained from influenza patients. During the outbreak of influenza in the spring of 1983 ELISA was successfully used for the rapid diagnosis of influenza, and some of its advantages in comparison with the conventional immunofluorescence test were thus demonstrated. To overcome difficulties arising from the low immunogenic potency of protein M, in the process of obtaining diagnostic sera and ascitic fluids the animals were immunized with the conjugate of protein M and polyelectrolite, which ensured considerable activation of humoral immune response.

Animals↗

[Influenza virus penetration into the cells of a continuous dog-kidney line].

The penetration of the influenza virus (WSN) into MDCK cells and its intracellular fate was studied using electron microscopy of ultrathin sections of infected cells at early steps of infection, and biochemical analysis of intracellular subviral components. In electron micrographs, the virus particles absorbed on the cells and located inside phagosomes were detected. In both the cases, the fusion of the virus with cell envelopes was distinctly seen. The fusion took place with incubation at 37 degrees C and 4 degrees C, thus suggesting a non-enzymatic mechanism. The inner virus component released into the cytosol after fusion represented virus cores, i. e. ribonucleoproteins (the final products of uncoating) surrounded by the inner protein membrane consisting of matrix (M) protein. The cores were accumulated in perinuclear cytoplasm of infected cells and were most probably intermediates in virus uncoating.

Adsorption↗