HIV-1 induces down-regulation of bcl-2 expression and death by apoptosis of EBV-immortalized B cells: A model for a persistent 'self-limiting' HIV-1 infection

Interactions between HIV-1 and EBV were studied in HIV-1-infected EBV- positive lymphoblastoid B cells. Following in vitro exposure of B cells to HIV-1, the number of infected cells reached a plateau (25-35%) in approximately 20 days and remained fairly stable thereafter, despite the presence of infectious virus in culture supernatants. HIV-1-positive (gp120⁺) were separated from HIV-1-negative (gp120^-) cells, and the two fractions were further characterized for EBV antigens, bcl-2 expression, and growth capacity in vitro. Compared to gp120^- cells, EBNA 1, EBNA 2, and LMP 1 were down-regulated, and the episomal form of EBV-DNA was dramatically decreased in the gp120⁺ cells. When plated in culture gp120⁺, but not gp120^-, cells died; BZLF1 antigen was not expressed, thus ruling out a reactivation of the EBV lytic cycle. Cytofluorometric, morphological, and molecular analyses disclosed that gp120⁺ cell death was due instead to apoptosis; evidence of bcl-2 down-regulation in these cells was consistent with this finding. gp120⁺ cell apoptosis contributed to keeping the level of HIV-1-infected cells at a steady state in the unfractionated culture, where persistent infection was maintained by HIV-1 transmission to B cells newly arising from the proliferation of HIV-1-uninfected cells.