Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
ROLE OF THE HIV VPR AND ENVELOPE PROTEINS IN VIRAL INFECTIVITY AND CYTOPATHOGENICITY
Diss Abstr Int [B]; 52(6):2907 1991. Unique Identifier : AIDSLINE ICDB/92679372 Dedera DA; Washington Univ.
Abstract:
The functional importance of many of the genes of the HIV genome in viral infectivity and cytopathogenicity has been demonstrated, although there remain several identified genes of undetermined function. The role of the vpR protein in the HIV life cycle and the transmembrane envelope protein (TM) in HIV infectivity, syncytia formation and cytopathogenicity were examined here. The vpR gene in the parental proviral HIV-1 clone HXB2 was truncated via site-directed mutagenesis and found to be unessential for viral infectivity, replication and cytopathogenicity. In contrast, the envelope gene is known to be involved in viral infectivity, syncytia formation and cytopathogenicity, although the role of syncytia in the HIV cytopathic effect is not clear. Structural alterations in the envelope protein were used to further delineate its functional relevance in the HIV-1 life cycle. The role of oligosaccharides in proper envelope functions was examined with N-butyldeoxynojirimycin (N-buDNJ), an inhibitor of glucosidase I and II processing enzymes. N-buDNJ-treated HIV-infected cells were unable to produce syncytia and were found to produce virus with reduced infectivity. The role of the TM in HIV infectivity and cytopathogenicity was examined by mutagenesis. Mutations in the fusion domain of the TM resulted in mutant viruses with attenuated (F3) or a complete loss (F6) of syncytia-forming capacity. Both viruses had reduced infectivity in T cell lines. The cytopathic effects of syncytia were observed with the HXB2- and F3-infected cells, whereas the F6 virus maintained single-cell lysis in the absence of syncytia, demonstrating two cytopathic mechanisms. Additionally, an increase in virus yield was observed with F6-infected cells, resulting from the loss of the syncytial cytopathic effect. Expression of the F3, F6 and HXB2 envelope proteins in recombinant vaccinia virus in the absence of other HIV proteins revealed similar impairment of syncytia-forming capacity. Analysis of the vaccinia-expressed envelope proteins revealed otherwise normal structure and function of the mutant compared to wild-type envelope proteins. Mutations of two highly conserved cysteine residues in the TM resulted in mutant viruses which had lost all infectivity. Vaccinia recombinants which expressed these mutant envelope proteins revealed a defect in the processing of the gp 160 precursor into the surface and TM envelope proteins. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD91-34367).
Keywords: alpha-Glucosidases/ANTAGONISTS & INHIB Gene Products, vpr/*GENETICS Giant Cells Glucosamine/*ANALOGS & DERIVATIVES/PHARMACOLOGY HIV-1/*GENETICS/PHYSIOLOGY Mutation Viral Envelope Proteins/*GENETICS THESIS 920630
M9261021
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Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
