Dual role of the HIV-1 vpr protein in the modulation of the apoptotic response of T cells.
We investigated the effect of vpr, physiologically expressed during the course of an acute HIV-1 infection, on the response of infected cells to apoptotic stimuli as well as on the HIV-induced apoptosis. At 48 h after infection, Jurkat cells exhibited a lower susceptibility to undergo apoptosis with respect to uninfected cells. This effect was not observed following infection with either a vpr-mutated virus or a wild-type strain in the presence of antisense oligodeoxynucleotides targeted at vpr mRNA. Single-cell analysis, aimed at simultaneously identifying apoptotic and infected cells, revealed that resistance to apoptosis correlated with productive infection. Notably, vpr-dependent protection from induced apoptosis was also observed in HIV-1-infected PBMC. In contrast, at later stages of infection, a marked increase in the number of cells spontaneously undergoing apoptosis was detected in infected cultures. This virus-induced apoptosis involved vpr expression and predominantly occurred in productively infected cells. These results indicate that HIV-1 vpr can exert opposite roles in the regulation of apoptosis, which may depend on the level of its intracellular expression at different stages of HIV-1 infection. The dual function of vpr represents a novel mechanism in the complex strategy evolved by HIV to influence the turnover of T lymphocytes leading to either viral persistence or virus release and spreading.
Conti
L
L
Laboratories ofVirology and Ultrastructures, Istituto Superiore di Sanità, Rome, Italy; and Shionogi Institute for Medical Science, Osaka, Japan.
Matarrese
P
P
Varano
B
B
Gauzzi
M C
MC
Sato
A
A
Malorni
W
W
Belardelli
F
F
Gessani
S
S
D000208:Acute Disease; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D003513:Cycloheximide / Q000494:pharmacology; D016336:Gene Products, vpr / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D019169:Jurkat Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000821:virology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D010641:Phenotype; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D017735:Virus Latency / Q000276:immunology; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D054325:vpr Gene Products, Human Immunodeficiency Virus; D003513:Cycloheximide