title: Mapping of HIV-1 determinants of apoptosis in infected T cells.
abstract: HIV-1 infection leads to death of CD4(+) T cells in vivo and in vitro, although the mechanisms of this cell death are not well defined. We used flow cytometry to concurrently analyze infection and apoptosis of the CD4(+) CEM T cell line and human peripheral blood mononuclear cells (PBMC). Surprisingly, T cells productively infected with HIV-1 IIIB showed less apoptosis than control, uninfected T cells. This relative paucity of apoptosis was a characteristic of IIIB, since a large number of cells infected with the viral clone, HIV-1 NL4-3, were apoptotic. The nef, vpr, and vpu gene products were not responsible for apoptosis of NL4-3-infected cells, since NL4-3DeltaVprDeltaVpuDeltaNef and HXB-2 (a nef, vpr, and vpu triple mutant derived from IIIB) also killed infected cells. Moreover, only IIIB-infected cells showed a resistance to background levels of apoptosis. Thus, the apoptotic (and antiapoptotic) properties of HIV-1 do not map solely to mutations in nef, vpr, or vpu. We postulate that, in vivo, HIV variants that do not induce rapid apoptosis in the cells they infect may have a selective advantage.
authors.affiliation: Department of Pediatrics, Department of Medicine, National Jewish Medical & Research Center, 1400 Jackson Street, Denver, Colorado, 80206, USA.
authors.forename: E
authors.initials: E
authors.lastname: Rapaport
authors.forename: C R
authors.initials: CR
authors.lastname: Casella
authors.lastname: Ikl
authors.forename: F
authors.initials: F
authors.lastname: Mustafa
authors.forename: D
authors.initials: D
authors.lastname: Isaak
authors.forename: T H
authors.initials: TH
authors.lastname: Finkel
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D005434:Flow Cytometry; D015754:Genes, nef; D016334:Genes, vpr; D016338:Genes, vpu; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000502:physiology / Q000821:virology; D051379:Mice; D009154:Mutation; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology / Q000821:virology*
chemical_list: D016655:HIV Core Protein p24