I-102 Viral fitness costs and benefits of disrupting the host cell actin cytoskeleton in mucosal HIV-infection

Abstract

HIV-1 disrupts multiple processes that support the motility of infected host cells, including expression and proper localization of chemokine receptors, their downstream signal transduction machinery, and proteins regulating actin cytoskeletal turnover. While models have been developed to explain how these conserved lentiviral activities support HIV replication, their role and relative importance for HIV infection in vivo are largely unexplored. Recently, intravital microscopy studies in advanced humanized mouse models of HIV infection have enabled the visualization of the dynamic behavior of HIV-infected cells in the environmental context of lymphoid tissues, such as spleen and lymph node. Our lab is studying how HIV alters the migratory behavior of HIV-infected T cells in lymph nodes of BLT humanized mice, and how these alterations affect viral replication and persistence. We will present and discuss our recent findings on the roles of the HIV envelope, and the accessory Vpu, and Nef proteins in this context.