1887

Abstract

Human immunodeficiency virus type 1 (HIV-1) chronically infected (Cl) cell lines were established from HIV- linfected MT-4 cells that survived acute infection. The HIV gene expressed in the two longterm cultured cell lines differed from that of the lines cultured for shorter periods, by coding for a glycoprotein gp160 that had the C terminus deleted. One long-term cultured cell line, Cl-17, was studied in detail. An insertion of a premature stop codon in the gene caused about 90% of gp160 molecules to be truncated (gp160×), lacking both cytoplasmic and transmembrane domains; these species were secreted into the cell medium, and could form oligomers with other truncated gp160 molecules as well as with their normal counterparts. Cl-17 cells constantly yielded high levels of viral protein and relatively low quantities of infectious virus, without cytopathicity. However, acute infection of fresh MT-4 cells with CI-17-derived virus led to cytopathicity, the rate of which as well as the Env glycoprotein pattern depended on multiplicity: (i) using an infection dose of 10 ID/cell, cells died 7 to 8 days post-infection with normal gp160 synthesis predominating; (ii) with 10ID, gp160× was produced as early as 48 h postinfection and cell death was delayed. Predominant gp160× formation occurred again when new Cl cell lines were obtained with CI-17-derived virus. Thus, two human immunodeficiency virus variants, a normal and a defective one, are persistently expressed in CI-17 cells. The other long-term cultured Cl cell line also expressed gp160 with a similar (albeit slightly longer) deletion of a C-terminal region in most molecules, but the cell lines that were cultured for shorter periods did not. These results suggest that the emergence of HIV variants with a C-terminal deletion in the Env glycoprotein, which coexist with normal virus, may play a role in maintaining the long-term growth capacity and viability of Cl cells.

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1994-11-01
2024-04-19
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