Skip Navigation

Role of Cofilin in T Cell Function & HIV Pathogenesis

Loading video...

279 Views

Air date: Wednesday, May 29, 2019, 4:15:00 PM
Time displayed is Eastern Time, Washington DC Local
Views: Total views: 279
Category: Immunology
Runtime: 01:01:14
Description: Immunology Interest Group Seminar:

Cofilin is a member of the actin-depolymerizing factor (ADF)/cofilin family of proteins that bind and depolymerize filamentous actin (F-actin) to regulate actin dynamics. In human T cells, cofilin regulates T cell motility for T cell migration and homing to lymphoid and non-lymphoid tissues. Cofilin is also an essential player in T cell activation, during which cofilin is activated by co-stimulatory signaling, including signaling from CD28/B7 and integrins/ligand interactions (e.g. LFA-1/ICAM-1, α4β7/MAdCAM-1); cofilin activity is required for cortical actin polymerization to stabilize immunological synapse between T cells and antigen presenting cells. Cofilin activity is frequently targeted by intracellular pathogens for actin-dependent intracellular migration. Our previous studies have shown that in HIV latent infection of blood CD4 T cells, the virus utilizes the chemokine receptor, CXCR4 or CCR5, to triggers cofilin activity, which promotes cortical actin dynamics to facilitate viral entry and intracellular migration (Yoder et al., 2008, Cell, 134:782). Recently, we further demonstrated that HIV-mediated cofilin activity has pathogenic consequences in triggering chronic cofilin hyperactivation in the blood resting CD4 T cells of HIV patients. In this seminar, I summarize my over 15 years of research on HIV exploiting the cofilin pathway in T cells. I also discuss implications of HIV-mediated cofilin dysregulation in T cell dysfuction, chronic immune activation, and functional cure of HIV infection. Short biography: Dr. Yuntao Wu received his Ph.D training from the Department of Microbiology and Immunology at Queen’s University, Kingston, Ontario, Canada, studying baculovirus DNA replication. He had his postdoctoral training at NIMH/NIH, studying HIV infection of blood resting CD4 T cells and macrophages (Science, 2001, 293:1503-6). His lab at the National Center for Biodefense and Infectious Diseases, George Mason University mainly studies cell signaling in HIV infection of blood resting CD4 T cells and macrophages (Cell, 2008, 134,782). He focuses on studying how HIV is able to navigate through the complexes of cell signaling networks to exploit pathways for infection. For example, HIV uses the chemokine coreceptor CXCR4 or CCR5 for entry. However, HIV binding to these receptors also triggers signal transduction. He have been studying this HIV-mediated chemotactic signaling for over 15 years. His early study demonstrated a critical role of CXCR4/G-protein signaling in mediating cofilin activation and actin dynamics necessary for HIV nuclear migration and the infection of resting CD4 T cells (Cell, 2008,134:782). Recently, he also studied the pathogenic effects of HIV-mediated G protein signaling in HIV patients, and discovered chronic hyperactivation of cofilin in the blood resting CD4 T cells of HIV patients (Science Advances, 2019, 5:eaat7911). This recent study suggests an HIV-mediated systemic dysregulation of a T cell motility factor, which can impair T cell lymphatic entry and egress. This recent study also suggests that cofilin in a key molecule that may need to be therapeutically targeted for immune reconstitution to restore T cell motility. Currently, his lab is continuously studying the role of chemokine- and HIV-1-mediated G-protein signaling and actin dynamics in T cells.
Author: Yuntao Wu, Ph.D., Professor, School of System Biology, George Mason University
 
CIT Live ID: 33224
Permanent link: https://videocast.nih.gov/watch=33224