[Morphological analysis of a cell system, infected with different strains of the human immunodeficiency virus]. / Morfologicheskii analiz kletochnykh sistem, infitsirovannykh razlichnymi shtammami virusa immunodefitsita cheloveka.

Cell systems infected with 63 strains of types 1 and 2 HIV virus (HIV-1 and HIV-2) were examined under electron microscope. HIV virions were most frequently detected near the cell membrane or budding from it. In the cytoplasm HIV occurred only in vacuole-like formations. Accumulations of mature virions were seen in the cell-to-cell space. Mature particles of HIV-1 and HIV-2 differed by their morphology from oncoviral C particles and were similar rater to the Visna/Medi type Lentiviruses. Morphological analysis of HIV strains isolated in Russia demonstrated their similarity to be foreign HIV strains.

[Inhibitors of ADP ribosylation as antiviral agents: an experimental study in a model of HIV infection]. / Ingibitory ADF-ribozilirovaniia kak protivovirusnye sredstva: éksperimental'noe izuchenie na modeli VICh-infektsii.

The paper deals with further search for substances modifying metabolic processes, changing the conditions of virus existence in the host cell and, consequently, possessing a certain antiviral activity. The antiviral effects of aromatic carbonic acids amides including trisubstituted benzamides and nicotinamide were tested. Five out of 8 substances tested possessed antiviral activity which might be due to their capacity to inhibit the activity of the enzymes of ADP-ribosylation. By blocking cellular processes of ADP-ribosylation, the substances under study depressed DNA capacity for reparation, inhibited differentiation and transformation of cells, i.e. had an indirect effect on reproduction of viruses. The universal nature of the processes coursing with participation of NAD(+)-dependent ADP-ribosylation suggests that the range of antiviral activity of inhibitors of mono- and poly-ADP-ribosylation would not be limited to HIV infection but would be rather wide.

[3'-Mercapto-3'-deoxythymidine-5'-triphosphate as a terminator of DNA synthesis catalyzed by RNA-dependent DNA-polymerases]. / 3'-Merkapto-3'-dezoksitimidin-5'-trifosfat kak terminator sinteza DNK, kataliziruemogo RNK-zavisimymi DNK-polimerazami.

3'-Mercapto-3'-deoxy-TTP was synthesized and tested as DNA chain terminator nucleotide for calf thymus alpha DNA polymerase, E. coli DNA polymerase I (Klenow fragment), terminal deoxyribonucleotidyltransferase (Bollum enzyme) and reverse transcriptase from AMV- and HIV-I-viruses. It was shown that the compound terminates DNA chain elongation by reverse transcriptases selectively and irreversibly. Other tested DNA polymerases do not use this nucleotide analogue as a substrate. 3'-Mercapto-3'-deoxythymidine was tested on lymphoblastoid T-cell line MT-4 with HIV-viruses and shown to suppress viruses as efficiently as 3'-azido-3'-deoxythymidine.

Karyological approach to the identification of true cell lines susceptible to the human immunodeficiency virus (HIV).

A karyological analysis of twenty-two variants of eight cell lines, which differed in their susceptibility to the human immunodeficiency virus (HIV) and which had been obtained from different sources, was carried out by means of differential chromosome staining for G and C bands. The karyotypes of eight T-lymphoblastoid cell lines were identified, including five (MT-4, Molt-3, CEM, H-9, and Hut-78) not previously studied by cytogenetic methods. Karyotyping confirmed the identity of seventeen variants of the eight cell lines, and five variants of four lines were found to be misidentified. Comparative analysis of the cytogenetic characteristics of the three CEM-line variants demonstrates the need for karyotype evaluation in the course of in vitro cell cultivation. Fourteen identical marker chromosomes were revealed in H-9 and Hut-78 cell karyotypes, confirming the common origin of these two lines. It was found that the cells of the HIV-susceptible lines had a tendency to undergo polyploidisation both during the initial stages after isolation and in the course of cultivation.

[Inhibition of HIV reproduction in cell culture by 5'-phosphonates of 3'-azido-2',3'-dideoxynucleosides]. / Ingibirovanie reproduktsii virusa immunodefitsita cheloveka v kul'ture kletok 5'-fosfonatami 3'-azido-2',3'-dideoksinukleozidov.

The antiviral activity of 3'-azido-2',3'-dideoxynucleoside 5'-phosphate analogues: 5'-phosphonomethylene-3'-azido-2',3'-dideoxythymidine, 5'-methylphosphonate and 5'-phosphite of 3'-azido-2',3'-dideoxythymidine, 5'-phosphites of 3'-azido-2',3'-dideoxyadenosine and guanosine was investigated in HIV-infected cell cultures (human lymphoblastoid cells). The effectivity of inhibition of HIV-reproduction in cells by these substances was close or even higher than that for the corresponding 3'-azido-2',3'-dideoxynucleosides, whereas their toxicity was lower than that of nucleosides. These substances are supposed to be transported into the cells and to be transformed into the corresponding 5'-triphosphate analogues under the action of cell kinases. It is possible that such agents are terminator substrates of virus reverse transcriptases and thus inhibit the biosynthesis of DNA chains.

[Inhibition of HIV reproduction in cultured cells using proteolysis inhibitors]. / Podavlenie reproduktsii virusa immunodefitsita cheloveka v kul'ture kletok s pomoschch'iu ingibitora proteoliza.

Treatment of AIDS is a complicated problem since there is a limited set of preparations tested and most of them appear to be ineffective. Their main target is HIV reverse transcriptase. The data presented show that proteolysis inhibitors are able to inhibit HIV reproduction in cell culture. The compounds used in this study, gordox and kontrikal, are officinal drugs and therefore it is worthwhile to study their effect in patients with AIDS.

[The functional activity and count of the natural killer cells in patients with recently diagnosed diabetes mellitus types I and II]. / Izuchenie funktsional'noi aktivnosti i kolichestva estestvennykh kletok-killerov u bol'nykh s nedavno voznikshim sakharnym diabetom I i II tipa.

Eight patients with type I diabetes mellitus (D-I), seven patients with type II diabetes mellitus (D-11) and 8 healthy donors were examined. The disease standing did not exceed 1 year since the moment of the diagnosis establishment. The patients with D-I manifested activation of natural killers (NK) as compared to their activity in the donors and patients with D-II (76.05 +/- 6.5%, 52.33 +/- 9.55% and 55.39 +/- 10.63%, respectively, p less than 0.01) in the presence of the attenuated response of NK to interleukin-2 and alpha-interferon, determined by NK prestimulation. The amount of NK (CD16-positive) in D-I was significantly less than in the donors and patients with D-II. The high activity of NK in D-I correlated with an increase of receptor expression for transferrin on the mononuclear cells of peripheral blood. At the same time 5 out of the 8 patients with D-I and 2 patients with D-II out of the 7 demonstrated the rise of serum alpha-interferon (in the titer 1:40 and over). Activation of NK and the rise of serum interferon may be due to viral etiology of the disease and may play a role in the autoimmune process in patients suffering from D-I.

[The effect of 3'-azido-3'-deoxynucleosides on the reproduction of AIDS virus in cell culture]. / Deistvie 3'-azido-3'-dezoksinukleozidov na reproduktsiiu virusa SPID v kul'ture kletok.

Action of three nucleoside analogues with azido-group on AIDS virus (human immunodeficiency virus--HIV) reproduction was studied in two cell species. Among these compounds there were 3'-azido-3'-deoxythymidine (Az-T), 3'-azido-3'-deoxyarabinothymidine (Az-AT) and 3'-azido-2',3'-dideoxy-5-methylcytidine (Az-dCMe). All compounds prevent cells against HIV infection, but Az-T action was expressed more strongly. The reason for the lower activity of the Az-AT and Az-dCMe bases is probably stipulated by their poor conversion to the corresponding 5'-triphosphates. Az-T 5'-triphosphate blocks HIV reproduction due to the inhibition of the viral reverse transcriptase.

[Cultivation of cells producing the human immunodeficiency virus]. / Kul'tivirovanie kletok-produtsentov virusa immunodefitsita cheloveka.

The possibility of optimizing the conditions for the cultivation of cells producing human immunodeficiency virus (HIV) was explored. The stimulating effect on the cell cultures of interleukin-2 and specific anti-interferon antibodies was examined. The individual use of interleukin-2 or anti-interferon antibody preparations did not result in any marked enhancement of HIV virus reproduction in the cells, whereas combining of interleukin-2 which stimulated proliferation of T-lymphocytes with poly- and monoclonal anti-interferon antibodies proved to be effective increasing the expression of virus-specific antigens in the cells 1.5-fold. It seems expedient to carry out further screening of different reagents and combinations thereof capable of significantly increasing HIV virus reproduction in cell cultures which would serve as the antigen for diagnostic systems.

[The search for preparations suppressing the reproduction of the AIDS virus]. / Poisk preparatov, podavliaiushchikh reproduktsiiu virusa SPID.

Trials of clinically advantageous national inducers, thymus hormones, as well as human recombinant alpha 2-interferon were carried out in cultures of continuous lymphoblastoid cells H9/IIIB infected with HIV virus. The virus-inhibiting effect for HIV was observed with interferon in doses of 10-100 IU/ml. At a concentration of interferon of 1000 IU/ml, virus replication was inhibited completely, the interferon doses used exerting no marked toxic or antiproliferative effect on the cells. Human interferon inducers, poly(G).poly(C), PXL-6, dsRNA in concentrations of 50-100 micrograms/ml inhibited virus reproduction significantly. The highest antiviral effect was achieved with yeast dsRNA. The preparations of immunomodulators, thymarin, the 5th and 7th fractions of thymosin, noticeably stimulated proliferation of infected T-lymphocytes, reducing the relative number of cells carrying the virus-specific antigen. Combined use of preparations with different mechanisms of the antiviral effect may be advantageous in prevention and treatment of AIDS.

[Antibodies reacting with the antigens of the human immunodeficiency virus in systemic lupus erythematosus]. / Antitela, reagiruiushchie s antigenami virusa immunodefitsita cheloveka pri sistemnoi krasnoi volchanke.

A study was made of the level of anti-HTLV-111 using an enzyme immunoassay (Emzygnost-anti-HTLV-111) in 75 donors and 143 patients with various diseases including SLE (57), rheumatoid arthritis (9), Sjögren's disease (3), Bekhterev's disease (2), polymyositis (2), dilatation cardiomyopathy (30), and acute lymphocytic leukemia (40). Anti-HTLV-111 were detected in 26 SLE patients and in one patient with polymyositis. A study of positive sera using immunoblotting showed no interaction with virus antigens. A conclusion was made that the detection of anti-HTLV-111 in systemic rheumatoid diseases was a false-positive result.