Credentials: Oncology Department
Position title: Cell biology of HIV replication
Phone: (608) 890-2551
501 Robert M Bock Lab
1525 Linden Dr
Madison, WI 53706
Virology; Cancer Biology; RNA Biology
We are interested in the interplay between retroviruses and their cellular hosts during the course of viral replication. Our current focus is on the cell biology of the human immunodeficiency virus type 1 (HIV-1) that causes the acquired immunodeficiency syndrome (AIDS). All viruses are obligate intracellular organism. Because retroviruses encode a DNA intermediate that must be inserted into the host cell’s genome and maintained (sometimes for years and years), HIV-1 and other retroviruses are remarkably adept at exploiting host cellular enzymes and trafficking machineries to assist with their replication. We have two core projects, both of which study cellular and molecular aspects of HIV-1 replication. In the first, we are studying species-specific molecular blocks affecting HIV-1 virus assembly. For example, we recently uncovered a block to HIV-1 mRNA nuclear export in cells derived from mice and attributable to a polymorphism in the murine ortholog of the cellular CRM1 (mCRM1) nuclear export receptor. We are currently trying to understand why mCRM1 blocks HIV-1 trafficking, and these studies have recently led us to exciting new questions pertaining to viral and cellular regulatory aspects of subnuclear and nucleus-to-cytoplasm mRNA trafficking. In the second project, we are studying how retroviruses exploit virus-induced cell-cell adhesion zones known as virological synapses (VS) to promote their efficient transmission. We have found that viral Envelope glycoproteins mediate the formation of the VS and subsequently signal virion assembly at these sites of cell-cell contact. The spread of infection is regulated by a cell-mediated actin-driven flow of virus particles from cell-to-cell. These studies have relevance to plasma membrane organization, cell-cell signaling, cytoskeletal trafficking and microbial pathogenesis.