HIV-1 Tat protein and its inhibitor Ro 24-7429 inhibit lymphocyte proliferation and induce apoptosis in peripheral blood mononuclear cells from healthy donors.
To explore further the effects of the HIV-1 transactivator protein Tat on human lymphoid cell function we examined the effects of Tat on lymphocyte proliferation and programmed cell death (apoptosis). We found that the HIV-1 Tat protein induced apoptosis and inhibited lymphocyte proliferative responses in lymphocytes obtained from healthy HIV-1 seronegative donors. Surprisingly, the Tat inhibitor Ro 24-7429 also induced apoptosis and inhibited antigen-induced lymphocyte proliferation. In checkerboard experiments, each agent could antagonize the effects of the other in both assays. These data suggest that Tat and its inhibitor may interact with a host element critically important in the processes of lymphocyte proliferation and programmed cell death. The HIV-1 Tat protein may affect both lymphocyte survival and function in HIV-1 infection, thereby contributing to the immune deficiency of HIV-1 disease.
Patki
A H
AH
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Lederman
M M
MM
D000998:Antiviral Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001569:Benzodiazepines / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015696:Gene Products, tat / Q000494:pharmacology*; D015497:HIV-1; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D011758:Pyrroles; D054322:tat Gene Products, Human Immunodeficiency Virus
D000998:Antiviral Agents; D015696:Gene Products, tat; D011758:Pyrroles; D054322:tat Gene Products, Human Immunodeficiency Virus; D001569:Benzodiazepines; C070024:Ro 24-7429