A human T-cell line resistant to cytopathic effects of the human immunodeficiency virus (HIV)

Abstract

Infection of human helper T lymphocytes with the human immunodeficiency virus (HIV) results in a rapid induction of cytopathic effects and cell lysis. We isolated a variant of the human T-lymphoblastoid cell line, CEM, that is fully susceptible to HIV infection but resistant to virally induced cytopathic effects. Exposure of the cells, designated CR10, to HIV resulted in the expression of viral antigens in 100% of cells within 6–9 days. Virus-infected cells remained fully viable and could be cultivated under standard culture conditions for a desired period of time. Parental CEM cells died within 9–12 days after HIV infection. Proviral DNA could be detected in the HIV-infected CR-10 cells by Southern blot and molecular hybridization 4–5 days after infection; the relative amount of proviral DNA reached maximum at Days 6–10 and remained stable during an 8-month follow-up period. Virus production by HIV-infected CR-10 cells was documented by electron microscopy and detection of reverse transcriptase activity in cell culture supernatants. HIV-infected CR-10 cells exhibited a down modulation of the OKT-3, OKT-4, OKT-4A, OKT-8, and OKT-11 T-cell surface markers, but not of the OKT-9 (transferrin receptor). One of the HIV persistently infected CR-10 cell clones has been kept in continuous culture for over 8 months. During this period, the cells remained fully viable, 100% positive for HIV antigens, and negative for most of the T-cell surface markers tested and continued to produce biologically active HIV. The CR-10 and HIV-infected CR-10 cell lines will be useful in studies on the biology of HIV and in the isolation and large-scale propagation of this virus.