12:00pm - 1:00am|
Department of Microbiology & Immunology Seminar Series
Lee Ratner, MD, PhD
Professor, Department of Medicine, Oncology Division,
Medical Oncology Section, Molecular Oncology Section
Department of Molecular Microbiology
Department of Pathology & Immunology
Washington University School of Medicine in St. Louis
" Comparative Human Retrovirus Pathogenesis "
Host: Jian Zhu
Seminar Abstract: HIV-1 caused the global AIDS epidemic, but HIV-2 is attenuated. The restriction factor SAMHD1 limits HIV-1 replication in noncycling cells. HIV-2 overcomes this restriction via the accessory protein Vpx, which targets SAMHD1 for degradation through interaction with ubiquitin ligase adaptor DCAF1. We identified cyclin L2 as a DCAF1-interacting protein required for HIV-1 replication in macrophages. Vpx was also found to bind interferon regulatory factor 5, and inhibit Toll-like receptor-mediated cytokine activation. Understanding the mechanism of HIV immunomodulation is important for overcoming latency and vaccine development.
Human T-cell virus type 1 (HTLV-1) causes an aggressive CD4+ T cell malignancy, whereas HTLV-2 is not leukemogenic. HTLV-1 oncoprotein, Tax1, includes a PDZ domain binding motif (PBM) lacking from Tax2, and induces Akt phosphorylation by inhibiting PI3K-Akt regulatory phosphatases. Tax1 also induces genetic instability, at least partially by inducing nitrogen oxide synthetase. Definition of these pathways provides novel methods of treatment or chemoprevention.
|Location: ||Upper Auditorium, Rm 3-7619|
Posted by: Nicole Beaumont, Micro & Immunolgy, 8-Apr-15 12:18pm ET