HIV-1 MEDIATES RAPID APOPTOSIS OF LYMPHOCYTES FROM HUMAN CD4 TRANSGENIC BUT NOT NORMAL RABBITS

Normal rabbit lymphocytes can be infected with HIV-1 although infectio n is much less efficient than in human lymphocytes. When peripheral bl ood mononuclear cells (PBMC) from rabbits transgenic for human CD4 (Hu CD4) were exposed to HIV-1, enhanced infection and a rapid depletion o f lymphocytes were observed. Cell death in the infected cultures occur red via apoptosis, but no similar effect was seen in nontransgenic rab bit PBMC cultures. induction of apoptosis in HuCD4-expressing cells re quired virus replication; heat-inactivated Virus or recombinant viral proteins had no effect on cell viability. Expression of the Fas antige n was increased in HIV-l-infected CD4(+) rabbit lymphocytes. Character ization of the infected PBMC cultures revealed that apoptosis occurs b oth in HuCD4(+) and HuCD4(-) cells, indicating that bystander cells ar e killed. These data define a requirement for HuCD4 in initiation, but not the spread, of HIV-1-induced apoptosis in rabbit PBMC and provide a model to probe mechanisms leading to lymphocyte depletion in HIV-1 infection. (C) 1995 Academic Press, Inc.