expression of the human immunodeficiency virus type 1 (hiv-1) nef gene during hiv-1 production increases progeny particle infectivity independently of gp160 or viral entry.

NLM AIDSLINE Expression of the human immunodeficiency virus type 1 (HIV-1) nef gene during HIV-1 production increases progeny particle infectivity independently of gp160 or viral entry. Miller MD; Warmerdam MT; Page KA; Feinberg MB; Greene WC; Gladstone
March 30, 1995

J Virol. 1995 Jan;69(1):579-84. Unique Identifier : AIDSLINE The nef gene product of human immunodeficiency virus type 1 (HIV-1) promotes more-rapid kinetics of viral replication in primary peripheral blood mononuclear cells. We have previously shown that these enhancing effects of Nef on HIV-1 replication reflect an increase in viral infectivity detectable both in limiting dilution assays and through a single-cycle infection of the HeLa-CD4-long terminal repeat-beta-galactosidase indicator cell line. We now demonstrate that nef-defective HIV-1 can be rescued to near wild-type levels of infectivity by coexpressing Nef in trans in the cell line producing the virus. This observation indicates that HIV-1 virions produced in the presence of Nef are intrinsically different. However, we show that the major viral structural proteins are quantitatively similar in purified viral preparations. We also demonstrate the functional equivalence of the gp120-gp41 envelope glycoprotein complexes of Nef+ and Nef- HIV-1 through an assay for viral entry. Finally, we show that env-defective Nef+ HIV-1 pseudotyped with an amphotropic envelope is also more infectious than similarly pseudotyped Nef- HIV-1. Thus, the production of HIV-1 in the presence of Nef results in viral particles that are more infectious, and this increased infectivity is manifested at a stage after viral entry but prior to or coincident with HIV-1 gene expression. Cells, Cultured Gene Products, env/PHYSIOLOGY Genes, nef Genetic Complementation Test Hela Cells Human HIV-1/GENETICS/PHYSIOLOGY/PATHOGENICITY Membrane Fusion Protein Precursors/PHYSIOLOGY Support, Non-U.S. Gov't Virion/PATHOGENICITY Virus Replication/*GENETICS JOURNAL ARTICLE

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Information in this article was accurate in March 30, 1995. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.