Altered replication of human immunodeficiency virus type 1 (HIV-1) in T cell lines retrovirally transduced to express herpesvirus saimiri proteins StpC and/or Tip

Human peripheral blood T lymphocytes are transformed in vitro to continuous proliferation by Herpesvirus saimiri subgroup C strains. It has been previ ously shown that H. saimiri-transformed human T cell lines are a permissive system for HIV-1 and 2 replication and are highly susceptible to infection by HIV-1 and 2. Two open reading frames of H. saimiri, StpC and Tip, are r equired for T cell transformation and are unique to this herpesvirus. The s uccessful transduction of human T cells with retroviral vectors expressing H. saimiri proteins StpC and Tip has allowed us to extend the previously me ntioned observations and investigate the role of StpC and Tip in replicatio n of HIV-1 T-tropic strains (IIIB, MN, and RF) in human T cell lines. StpC expression in Molt4 dramatically enhanced HIV-1 replication as measured by Tat protein expression, syncytia formation, and accumulation of reverse tra nscriptase activity. In contrast, Tip expression in Molt4 cells inhibited H IV-1 replication and cytopathic effects relative to Molt4 cells transduced with the empty vector alone. The StpC-induced phenotype dominated in Molt4 cells transduced to express both StpC and Tip, suggesting that StpC is resp onsible for facilitating HIV-1 replication in H. saimiri-transformed T cell s. Colony-forming ability of Tip-expressing Molt4 cells following HIV-1 inf ection was greatly enhanced over Molt4 cells expressing either StpC or no H . saimiri proteins at all. HIV-1 proviral DNA could be detected by PCR in s urviving Molt4 cells expressing StpC or Tip, indicating that a persistent i nfection was established. A better understanding of the effects of Tip and StpC proteins on the biology of human hemopoietic stem cells may lead to no vel therapeutic interventions for the treatment of AIDS. (C) 1999 Academic Press.