The biology of HIV assembly and viral infection through virological synapses
During infection of T cells with HIV-1, the causative agent of AIDS, each viral protein interacts with and utilizes numerous cellular factors to propagate the infection. We are interested in understanding the complex cellular and molecular interactions that promote viral replication and immune cell depletion. A major focus of our group has been understanding how the spread of HIV in cell culture facilitated by adhesions that form between infected and uninfected cells called virological synapses (VS). Live imaging studies indicate that cell adhesion and cell signaling trigger the directional movement of viral proteins to form VS. At VS viral assembly and production are connected with transfer and entry into target cells. We are actively studying the unique entry pathways that are mediated by VS. In addition to enhancing the efficiency of infection, virological synapses can have a direct impact on antiviral strategies. To block VS-mediated infections, some antiviral drugs and neutralizing antibodies are required at higher concentrations than those needed to adequately block infection by homologous cell-free virus. Our overarching goal is to understand viral assembly and transmission are coordinated by VS to facilitate the spread of HIV within the body. We are examining key cellular factors and events in assembly and transmission during HIV infection. We are studying how VS can promote immune evasion by studying neutralizing antibody responses, and examining how VS promotes the spread within primary lymphoid tissues using intravital imaging approaches. A better understanding of VS-mediated infection may guide the development of more potent drugs, vaccines, and microbicides.