HIV-1 Vpr does not inhibit CTL-mediated apoptosis of HIV-1 infected cells.
HIV-1 infected persons develop a robust CTL response to HIV antigens, yet HIV-1 is able to evade this host response and successfully replicate. The mechanism(s) of evasion is not completely defined but has been suggested to include resistance of infected cells to CTL-mediated apoptosis. The HIV-1 Vpr protein induces G2 arrest by indirectly inhibiting activation of cyclin B/p34cdc2 kinase. Granzyme B, the principle mediator of CTL-induced apoptosis, prematurely activates this same kinase complex. Therefore, we assessed the susceptibility of HIV-1 infected cells to CTL-mediated apoptosis to determine whether the expression of Vpr protected the infected cells from CTL-induced apoptosis. Antigen-specific CD8(+) CTL were able to induce apoptosis in HIV-1 infected cells and cells labeled with peptide corresponding to the CTL epitope with equivalent efficiency. This demonstrates that neither HIV-1 Vpr nor any other HIV protein directly inhibits CTL effector functions. Furthermore, we confirm that HIV-1 Nef is able to provide partial protection from CTL recognition of infected cells. Thus, the inability of CTL to control HIV-1 infection is likely not due to direct inhibition of CTL-mediated apoptosis.
Lewinsohn
Deborah A
DA
Department of Pediatrics, Oregon Health and Sciences University, 707 SW Gaines Road, CDRCP, Portland, OR 97201, USA. lewinsde@ohsu.edu
Lines
Rebecca
R
Lewinsohn
David M
DM
Riddell
Stanley R
SR
Greenberg
Philip D
PD
Emerman
Michael
M
Bartz
Steven R
SR
D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002460:Cell Line; D016336:Gene Products, vpr / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus