A major human immunodeficiency virus type 1-initiated killing pathway distinct from apoptosis.

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

A major human immunodeficiency virus type 1-initiated killing pathway distinct from apoptosis.

J Virol. 1997 Dec;71(12):9753-63. Unique Identifier : AIDSLINE MED/98037692
Kolesnitchenko V; King L; Riva A; Tani Y; Korsmeyer SJ; Cohen DI; Division of Basic Sciences, National Cancer Institute, National; Institutes of Health, Bethesda, Maryland 20892-4255, USA.

Abstract: We have investigated the relative contribution of apoptosis or programmed cell death (PCD) to cell killing during acute infection with T-cell-tropic, cytopathic human immunodeficiency virus type 1 (HIV-1), by employing diverse strategies to inhibit PCD or to detect its common end-stage sequelae. When Bcl-2-transfected cell lines were infected with HIV-1, their viability was only slightly higher than that of control infections. Although the adenovirus E1B 19-kDa protein has been reported to be a stronger competitor of apoptosis than Bcl-2, it did not inhibit HIV-mediated cell death better than Bcl-2 protein. Competition for Fas ligand or inactivation of the Fas pathway secondary to intracellular mutation (MOLT-4 T cells) also had modest effects on overall cell death during acute HIV infection. In contrast to these observations with HIV infection or with HIV envelope-initiated cell death, Tat-expressing cell lines were much more susceptible (200% enhancement) to Fas-induced apoptosis than controls and Bcl-2 overexpression strongly (75%) inhibited this apoptotic T-cell death. PCD associated with FasR ligation resulted in the cleavage of common interleukin-1beta-converting enzyme (ICE)-protease targets, poly(ADP-ribose) polymerase (PARP) and pro-ICE, whereas cleaved products were not readily detected during HIV infection of peripheral blood mononuclear cells or T-cell lines even during periods of extensive cell death. These results indicate that one important form of HIV-mediated cell killing proceeds by a pathway that lacks the characteristics of T-cell apoptosis. Our observations support the conclusion that at least two HIV genes env and tat) can kill T cells by distinct pathways and that an envelope-initiated process of T-cell death can be discriminated from apoptosis by many of the properties most closely associated with apoptotic cell death.

Keywords: *Apoptosis *Gene Products, tat/METABOLISM *HIV-1/PHYSIOLOGY
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