engleski

MCMV inhibits apoptosis to ensure its proliferation in host cell

All kinds of stress, including viral infection, can initiate signaling pathways leading to apoptosis. Elimination of infected cells via programmed cell death (PCD) can be effective as an antiviral innate defense mechanism since viruses depend on host cell machinery for their replication. Apoptosis activation is regulated by pro- and antiapoptotic proteins of Bcl-2 family which differ in the number of Bcl-2 homology (BH) domains. Antiapoptotic Bcl-2 proteins are antagonized by the proapoptotic Bak and Bax, and the so-called BH3-only proteins. Consequently, many viruses have evolved genes which encode for antiapoptotic proteins and contribute to their survival. A number of viruses express proteins homologous to the cellular antiapoptotic Bcl-2 proteins. Different strategy is pursued by cytomegaloviruses (CMVs) and other β-herpesviruses. Murine cytomegalovirus (MCMV) encodes two separate mitochondrial proteins. The first one is encoded by ORF m38.5 and specifically inhibits Bax protein (Jurak et al., 2008). The second, recently identified and characterized (Çam et al., 2010), is a product of m41.1 ORF, which functions as a viral inhibitor of Bak oligomerization. In addition to published in vitro data, here we studied the lack of m41.1 and its importance to viral proliferation in mouse model. We showed that m41.1 mutant virus is attenuated during early phase of infection in C57BL/6J mice. However, this is abolished in Bak-deficient mice. These results underscore the importance of Bak-mediated apoptosis as a host defense mechanism against CMV but also viral manipulation of this mechanism in order to ensure replication and dissemination.

cytomegalovirus; BAK; apoptosis

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