Medicine and Health Sciences Commons^™

Multiple Autonomous Cell Death Suppression Strategies Ensure Cytomegalovirus Fitness, Pratyusha Mandal, Lynsey Nagrani, Liliana Hernandez, Anita Louise Mccormick, Christopher Dillon, Heather Koehler, Linda Roback, Emad S Alnemri, Douglas Green, Edward Mocarski

Department of Biochemistry and Molecular Biology Faculty Papers

Programmed cell death pathways eliminate infected cells and regulate infection-associated inflammation during pathogen invasion. Cytomegaloviruses encode several distinct suppressors that block intrinsic apoptosis, extrinsic apoptosis, and necroptosis, pathways that impact pathogenesis of this ubiquitous herpesvirus. Here, we expanded the understanding of three cell autonomous suppression mechanisms on which murine cytomegalovirus relies: (i) M38.5-encoded viral mitochon-drial inhibitor of apoptosis (vMIA), a BAX suppressor that functions in concert with M41.1-encoded viral inhibitor of BAK oligomerization (vIBO), (ii) M36-encoded viral inhibitor of caspase-8 activation (vICA), and (iii) M45-encoded viral inhibitor of RIP/RHIM activation (vIRA). Following infection of bone marrow-derived macrophages, the virus initially …