INHIBITION OF APOPTOSIS IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED CELLS ENHANCES VIRUS PRODUCTION AND FACILITATES PERSISTENT INFECTION

Apoptosis is one of several mechanisms by which human immunodeficiency virus type 1 (HIV-1) exerts its cytopathic effects. CD4(+) Jurkat T-c ell lines overexpressing the adenovirus E1B 19K protein, a potent inhi bitor of apoptosis, were used to examine the consequences of inhibitio n of apoptosis during acute and chronic HIV-1 infections. E1B 19K prot ein expression inhibited HIV-induced apoptosis, enhanced virus product ion, and established high levels of persistent viral infection. One E1 B 19K-expressing line appeared to undergo HIV-induced death via a nona poptotic mechanism, illustrating that HIV infection results in lymphoc yte depletion through multiple pathways. Increased virus production as sociated with sustained cell viability suggests that therapeutic appro aches involving inhibition of HIV-induced programmed cell death may be problematic.