Human immunodeficiency virus type 1 (HIV-1) chronically infected (CI) cell lines were established from HIV-1,~B/LA~-infected MT-4 cells that survived acute infection. The HIV env gene expressed in the two longterm cultured cell lines differed from that of the lines cultured for shorter periods, by coding for a glycoprotein gpl60 that had the C terminus deleted. One long-term cultured cell line, CI-17, was studied in detail. An insertion of a premature stop codon in the env gene caused about 90 % of gpl60 molecules to be truncated (gpl60x), lacking both cytoplasmic and transmembrane domains; these species were secreted into the cell medium, and could form oligomers with other truncated gpl60 molecules as well as with their normal counterparts. CI-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 -4 IDs0/cell, cells died 7 to 8 days post-infection with normal gpl60 synthesis predominating; (ii) with l0 -2 IDs0, gpl60x was produced as early as 48 h postinfection and cell death was delayed. Predominant gpl60x formation occurred again when new CI 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 CI cell line also expressed gpl60 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 CI ceils.

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