ABSTRACT
HIV-1 virions are as immature noninfectious particles lacking a central core. Shortly after budding, virions temporally mature and acquire cores and infectious activity. The cause of maturation remains poorly studied. We have revealed that the virions produced early after infection following 24-36 hours, never mature and remain noninfectious, and only virions produced 48-72 hours after infection mature. The mature virions contain 3 times more genomic viral RNA than "early" virus. The "early" virions contain the same proteolytically cleaved Gag proteins as mature virions in contrast to the accepted version. The virus protease inhibitor Indinavir sulfate (IS) fully blocks infectivity when added early after infection. The early proteolysis of Gag precursor in the infected cells and inclusion into the virions of cellularly cleaved matrix protein (cMA) are shown in the IS-treated cells. cMA is associated with genomic viral RNA.
Subject(s)
HIV Infections/virology , HIV-1/growth & development , HIV-1/metabolism , Protein Precursors/metabolism , Virus Assembly , gag Gene Products, Human Immunodeficiency Virus/metabolism , Cell Line , HIV Protease Inhibitors/metabolism , HIV Protease Inhibitors/pharmacology , HIV-1/pathogenicity , Humans , Indinavir/metabolism , Indinavir/pharmacology , Virulence/drug effects , Virus SheddingABSTRACT
AIM: Until now, the problem of effective therapy of HIV-infection is not resolved due to integrative type of interaction of HIV virus with target cell - T-lymphocyte. The study was aimed on search of method of deletion of HIV DNA-provirus from cell's genome. MATERIALS AND METHODS: Non-pathogenic for humans Mycoplasma arginini was used for coinfection of HIV-infected cells in model systems in vitro. RESULTS: Complex of mechanisms was documented leading to: blocking up to 50 - 60% of extracellular virus (according to titration results), cancel of apoptosis in infected cells stained on Hoechst, formation of defective vif(-) virions, which together with arginine-desaminase of M. arginini arrange permissive conditions for activation of cellular APOBEC3G with subsequent disruption of DNA- provirus and blocking of viral infection. As studies of ultrastructure showed, listed events resulted from direct interaction of HIV with mycoplasma. CONCLUSION: The elimination of HIV DNA-provirus is possible by co-infection of T-lymphocytes with M. arginini.
