Intrinsic susceptibility of rhesus macaque peripheral CD4(+) T cells to simian immunodeficiency virus in vitro is predictive of in vivo viral replication

Previous studies with simian immunodeficiency virus (SIV) infection of rhes us macaques suggested that the intrinsic susceptibility of peripheral blood mononuclear cells (PBMC) to infection with SIV in vitro was predictive of relative viremia after SIV challenge. The present study was conducted to ev aluate this parameter in a well-characterized cohort of six rhesus macaques selected for marked differences in susceptibility to SIV infection in vitr o. Rank order relative susceptibility of PBMC to SIVsmE543-3-infection in v itro was maintained over a 1-year period of evaluation. Differential suscep tibility of different donors was maintained in CD4(+) T-cell-depleted PBMC, macrophages, and CD4(+) T-cell lines derived by transformation of PBMC wit h herpesvirus saimiri, suggesting that this phenomenon is an intrinsic prop erty of CD4(+) target cells. Following intravenous infection of these macaq ues with SIVsmE543-3, we observed a wide range in plasma viremia which foll owed the same rank order as the relative susceptibility established by in v itro studies. A significant correlation was observed between plasma viremia at 2 and 8 weeks postinoculation and in vitro susceptibility (P < 0.05). T he observation that the two most susceptible macaques were seropositive for simian T-lymphotropic virus type 1 may suggests a role for this viral infe ction in enhancing susceptibility to SIV infection in vitro and in vivo. In summary, intrinsic susceptibility of CD4(+) target cells appears to be an important factor influencing early virus replication patterns in vivo that should be considered in the design and interpretation of vaccine studies us ing the SIV/macaque model.