Human immunodeficiency virus type 1 inhibits DNA damage-triggered apoptosis by a Nef-independent mechanism.
It is controversial whether the accessory human immunodeficiency virus type 1 (HIV-1) Nef protein inhibits or enhances apoptosis. To address this issue, we investigated the effect of Nef on programmed cell death with vectors or proviral HIV-1 constructs coexpressing Nef and green fluorescent protein from single bicistronic RNAs. This approach allows us to readily identify transfected or infected cells and to correlate cell death directly with Nef expression levels. We demonstrate that Nef does not significantly affect apoptosis in transfected or HIV-1-infected Jurkat T cells or primary human peripheral blood mononuclear cells. Unexpectedly, however, both nef+ and nef-defective HIV-1 infection blocked apoptosis in cells treated with UV light or etoposide but not cell death induced by CD95 antibody, TRAIL, Ly294002, or serum starvation. Our results show that HIV-1 infection inhibits DNA damage-induced but not death receptor-dependent cell death by a Nef-independent mechanism.
Schindler
Michael
M
Department of Virology, Universitätsklinikum, Albert-Einstein-Allee 11, D-89081 Ulm, Germany.
Münch
Jan
J
Kirchhoff
Frank
F
D017209:Apoptosis; D004249:DNA Damage; D005047:Etoposide / Q000494:pharmacology; D015693:Gene Products, nef / Q000235:genetics / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000528:radiation effects; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D014161:Transduction, Genetic; D014466:Ultraviolet Rays; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D019384:Nucleic Acid Synthesis Inhibitors; D054311:nef Gene Products, Human Immunodeficiency Virus; D005047:Etoposide