title: Live or let die: manipulation of cellular suicide programs by murine cytomegalovirus.
abstract: Cytomegaloviruses (CMVs) are large double-stranded DNA viruses that replicate slowly and cause life-long persisting infections in their hosts. To achieve this, the CMVs had to evolve numerous countermeasures against innate and adaptive immune responses. Induction of programmed cell death is one important host defense mechanism against intracellular pathogens such as viruses. For a multicellular organism, it is advantageous to let infected cells die in order to thwart viral replication and dissemination. For a virus, by contrast, it is better to inhibit cell death and keep infected cells alive until the viral replication cycle has been completed. As a matter of fact, the CMVs encode a number of proteins devoted to interfering with different forms of programmed cell death: apoptosis and necroptosis. In this review, we summarize the known functions of the four best characterized cell death inhibitors of murine cytomegalovirus (MCMV), which are encoded by open reading frames, M36, m38.5, m41.1, and M45. The viral proteins interact with key molecules within different cell death pathways, namely caspase-8, Bax, Bak, and RIP1/RIP3. In addition, we discuss which events during MCMV infection might trigger apoptosis or necrosis and how MCMV's countermeasures compare to those of other herpesviruses. Since both, MCMV and its natural host, are amenable to genetic manipulation, the mouse model for CMV infection provides a particularly suitable system to study mechanisms of cell death induction and inhibition.
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistr. 52, 20251 Hamburg, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Handke
authors.forename: Eva
authors.initials: E
authors.lastname: Krause
authors.forename: Wolfram
authors.initials: W
authors.lastname: Brune
mesh_terms: D000818:Animals; D017209:Apoptosis; D054884:Host-Pathogen Interactions; D057131:Immune Evasion; D051379:Mice; D018146:Muromegalovirus / Q000276:immunology* / Q000472:pathogenicity*; D011485:Protein Binding; D060066:Protein Interaction Maps; D014764:Viral Proteins / Q000378:metabolism; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D014764:Viral Proteins; D037521:Virulence Factors