DNA virus mechanisms of evading host defenses; translational control mechanisms
Adam P. Geballe received a B.A. degree from Stanford University before completing the M.D. degree at Duke University. He completed postgraduate training in internal medicine, infectious diseases and medical microbiology prior to joining the scientific staff of the Fred Hutchinson Cancer Research Center where he is now a Member. In addition to his faculty appointment in the Department of Microbiology, Dr. Geballe is a Professor of Medicine.
Human cytomegalovirus (HCMV) causes substantial morbidity and mortality, primarily in newborns and immunocompromised patients. Like other viruses, HCMV must evade myriad host cell antiviral defense mechanisms, among which is the shut off of overall protein synthesis mediated by the interferon-induced, double-stranded RNA (dsRNA)-activated protein kinase R (PKR). HCMV encodes two proteins, pTRS1 and pIRS1, that block PKR activation. Investigations of these proteins have revealed that, among other activities, they bind to dsRNA and to PKR and at least one is essential for viral replication. Current research in the Geballe lab aims to elucidate the detailed molecular interactions between pTRS1 and its binding partners PKR and dsRNA. Additional experiments are underway to understand how the evolutionary "arms race" between PKR and TRS1 homologues encoded by all primate CMVs have altered interactions between these proteins. A related line of research aims to identify the genes and mechanisms by which poxviruses evade host dsRNA-activated anti-viral pathways. These studies should reveal new insights into the host-virus interactions that are likely to be key determinants of the pathogenesis of viral infections and may have implications for the design of viral vaccines and vectors.