HIV‐1 Env can pseudotype HTLV‐I and provide envelope‐mediated protection against super‐infection

Abstract

Superinfection exclusion is the phenomenon whereby a virus infected cell becomes resistant to subsequent re‐infection with the same or a related virus. Human Immunodeficiency Virus (HIV) is one of the many viruses for which superinfection exclusion has been demonstrated. Three HIV proteins (Nef, Vpu and Env) have been implicated in mediating the effect; however, the mechanism of resistance has not been well described. Here we demonstrate that the HIV‐1 envelope protein (Env) when over‐expressed is sufficient to mediate superinfection exclusion. The mechanism appears to work at the cell surface CD4 receptor and is independent of CD4 down‐regulation and does not appear to involve either the CCR5 or the CXCR4 co‐receptor. These results challenge the assumption that down regulation of the CD4 receptor during infection is critical in preventing super infection. As an extension to our study, we have demonstrated that the Human T‐Cell Leukemia Virus (HTLV) can be pseudotyped using HIV Env. We have developed a replication competent HTLV‐1 virus that expresses the HIV‐1 (in place of the HTLV‐1) Env protein. With this chimeric virus, we plan to transduce CD4+ human T cells and demonstrate that these cells can be protected from HIV‐1 superinfection.This research was supported by NIAID intramural funds and a GCE phase 1 award from The Bill and Melinda Gates Foundation.