[Persistence of type 1 human immunodeficiency virus (HIV-1) in MT-4 cells in presence of alpha-interferon]. / Persistentsiia virusa immunodefitsita cheloveka tipa 1 (Vich-1) v prisutstvii alpha-interferona v kletkakh MT-4.

The development of HIV infection during serial passages of HIV-1 strains with different replication capacity was studied in the presence of natural human alpha-interferon (IFN-alpha). The virus activity was evaluated by accumulation of virus-specific proteins in cells and culture fluid, determined by Western blot method and analysis of viral DNA in the cells by polymerase chain reaction. IFN-alpha suppressed replication of HIV-1/IIIB and 1974. The replication of strain 1974 (with a 10-fold lower replicative activity than strain IIIB) was inhibited during the first passage and of strain IIIb during the second passage. After the fourth passage IFN-2 alpha completely suppressed the replication of strain 1974, and the virus activity did not manifest after 4 consecutive co-culturings of cells from fourth viral passage with intact cells without IFN-alpha. A population of viral particles whose replicative activity was virtually undetected in the presence of IFN-alpha seemed to persist during serial passages of strain IIIB in MT-4 cells. On the other hand, the virus replication was restored during the first co-culturing of cells from the virus subculture with intact cells in the absence of IFN-alpha. Presumably, an increase in the level of IFN-alpha in the blood of HIV-infected patients at late stages of AIDS is not accidental and is caused by appearance of more virulent variants of the virus.

[Inhibition of nuclear import of HIV-1 Vpr protein by Gag polyprotein in the process of virus-like particles formation]. / Ingibirovanie iadernogo importa belka VPR VICh-1 poliproteinom GAG v protsesse formirovaniia virusopodobnykh chastits.

For studies of intracellular Vpr transport and the effect of the HIV-1 Gag polyprotein on the process, a recombinant baculovirus strain was constructed, which directs the synthesis of Vpr fused with the baculovirus secretory polypeptide. During infection the majority of Vpr has been observed in the cell nuclear fraction. These data suggest that Vpr nucleophilic signal is more active than the secretory one. However, during Vpr and Gag co-expression in the baculovirus expression system, Vpr content in the nuclei is decreased, since this protein incorporates effectively into virus-like particles and forms stable complexes with Gag polyprotein. Presumably, the Vpr-Gag post-translational interactions are needed for the Vpr incorporation into virions and suppress the nuclear import of this protein.

[Interaction of gag polyprotein-precursors p55 and p48 with p160gag-pol during formation of virus-like particles of HIV-1 with recombinant strains of vaccinia virus]. / Vzaimodeistvie gag poliproteinov-predshestvennikov p55 i p48 s p160gag-pol pri formirovanii virusopodobnykh chastits VICh-1 rekombinantnymi shtammami virusa ospovaktsiny.

The polypeptide composition of HIV-I virus-like particles produced by CV-I cells during mono- and coinfection with recombinant vaccinia virus (rVV) strains containing the whole (p55) and carboxyterminal truncated (p48) gag genes and gag-pol sequence is studied. In monoinfection both the gag-strains actively produced virus-like particles consisting of non-processed p55Gag and p48Gag polyprotein without p6 domain. In case of a coinfection of the cells with one of these strains and the rVV producing p160Gag-Pol polyprotein the virus-like particles consisted of p24 protein and a negligible amount of non-processed Gag precursors. The share of p24 protein increased in proportion to the duration of coinfection and decreased with a reduction of multiplicity of infection with rVV carrying p160Gag-Pol. Hence, the absence of p6 domain does not influence the processing of Gag proteins during virus-like particles assembly and budding. In contrast to the natural systems of HIV-I development, in the rVV expression system the p6Gag domain virtually does not contribute to reactions between Gag and Gag-Pol precursors and to the particles' morphogenesis.