BCL-2 EXPRESSION FACILITATES HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-MEDIATED CYTOPATHIC EFFECTS DURING ACUTE SPREADING INFECTIONS

The cytopathic effects (CPE) resulting from the infection of CD4(+) T cells by human immunodeficiency virus (HIV) have generally been charac terized as single-cell killing associated with apoptosis and/or the ge neration of syncytia resulting from the direct cell-to-cell transmissi on of the virus, Little is known, however, about the cellular factors influencing host cell susceptibility to HIV-mediated CPE, Because expr ession of the antiapoptosis gene, bcl-2, enhances cell viability after exposure to cytotoxic agents or stimuli, the effect of bcl-2 expressi on on HIV infection of stably transfected T-cell clones was investigat ed, Unexpectedly, bcl-2 expression by these cells accelerated the kine tics of an acute spreading HIV infection, as evidenced by a rapid loss of culture viability associated with the appearance of CPE and revers e transcriptase activity in the culture supernatant. This unexpected e ffect of bcl-2 expression results from the arrest of syncytial apoptos is, directly facilitating the cell-to-cell transmission of HN. In addi tion, bcl-2 expression is associated with enhanced HIV replication as determined by HIV type 1-specific Western blot (immunoblot) analysis, These results suggest that the inhibition of apoptosis is essential fo r this mode of viral transmission.