Transfer of human CD4(+) T lymphocytes producing beta interferon in Hu-PBL-SCID mice controls human immunodeficiency virus infection

Beta interferon (IFN-beta) exerts pleiotropic antiretroviral activities and affects many different stages of the human immunodeficiency virus (HIV) in fectious cycle in IFN-treated cells. To explore whether transfer of genetic ally engineered human CD4(+) T cells producing constitutively low amounts o f IFN-beta can eradicate HIV in vivo, we developed a new Hu-PBL-SCID mouse model supporting a persistent, replicative HIV infection maintained by peri odic reinoculations of activated human CD4(+) T cells. Transferring human C D4(+) T cells containing the IFN-beta retroviral vector drastically reduced the preexisting HIV infection and enhanced CD4(+) T-cell survival and Th1 cytokine expression. Furthermore, in 40% of the Hu-PBL-SCID mice engrafted with IFN-beta-transduced CD4(+) T cells, HIV-1 was undetectable in vivo as well as after cocultivation of mouse tissues with human phytohemagglutinin- stimulated lymphoblasts. These results indicate that a therapeutic strategy based upon IFN-beta transduction of CD4(+) T cells may be an approach to c ontrolling a preexisting HIV infection and allowing immune restoration.