New Paradigms in HIV-1 Control and Pathogenesis: Interactions Between Soluble and Cell-Derived Molecules with the HIV-1 Envelope

The natural history of HIV infection is highly heterogeneous in different individuals, spanning from a stable asymptomatic condition to a rapid disease evolution. A major determinant of the pace of HIV disease progression is the in vivo level of viral replication, which is regulated by an intricate network of bioactive molecules, including both soluble immune modulators, like antiviral cytokines, along with resident cell surface receptors, particularly those that can be incorporated into budding virions during viral egress. Our research aims to precisely delineate the underlying interactions between soluble and cell-derived molecules with the HIV-1 envelope, providing new vulnerabilities on the virus that may lead to novel targets for therapy and prevention. More specifically, our work has characterized a novel antiviral chemokine, XCL1/Lymphotactin, that can bind directly to HIV virions to inhibit replication of a broad range of viral isolates, and more recently, we have identified a host cell protein, integrin a4b7, that can be incorporated into the external envelope of budding virions to affect virus homing in vivo. These findings provide new paradigms in HIV-1 control and pathogenesis, and may inform new approaches for HIV-1 prevention and treatment.