Type I Interferon Contributes to CD4 T Cell Depletion Induced by Infection with HIV-1 in the Human Thymus

Persistent induction of type 1 interferon (IFN) is associated with human immunodeficiency virus type 1 (HIV-1) infection. We report here that the pathogenic HIV strain R3A (HIV-R3A) induced high levels of type 1 IFN, while the nonpathogenicHIV-R3B showed no significant induction in human fetal thymus organ culture (HFTOC).We found that IFN contributed to the depletion of human T cells by HIV-R3A in a fusion-independent fashion. The R3B recombinant with the R3A Env V1V2 domain (R3B/A-V1V2) was able to induce type 1 IFN, which contributed to the increased depletion of T cells. Therefore, type 1 IFN induction plays a significant role inHIV-induced T cell depletion in the human thymus. Pathogenic infections of humans and rhesus macaques by human immunodeficiency virus (HIV) and simian immunode-ficiency virus (SIV), respectively, are characterized by gener-alized immune activation and progressive CD4 T cell depletion (3, 23). It has been proposed that chronic activation of inter-feron (IFN) production may play a role in CD4 T cell depletion and AIDS progression (1, 5, 8–10). Although in vitro studies have demonstrated that type 1 IFN can suppress HIV type