Poster Presentation 25th Lorne Cancer Conference 2013

Inhibitors of Mitochondrial Apoptotic Pathway in Parapox virusĀ  (#228)

Livleen Kaur 1 2 , Srishti Chugh 1 , Christine Hawkins 1
  1. La Trobe University, melbourne, VIC, Australia
  2. CRC for Biomarker Translation, Bundoora, VIC, Australia

Apoptosis or cell death is a vital process in the host defence against virus infection and many viruses encode proteins to overcome this defence. Some virally encoded proteins exhibit homology to cellular anti-apoptotic BCL-2 proteins. The precise mechanisms by which cellular anti-apoptotic BCL-2 proteins protect cells from apoptosis is not completely understood, and the role of viral BCL-2 homologues in virus propagation and diseases is yet to be determined as well.

ORFV125 encoded by Parapox virus, is a potent inhibitor of the mitochondrial pathway of apoptosis. This study is aimed at investigating if ORFV125 acts in a Bcl-2-like manner to inhibit apoptosis. As of now study has been established that ORFV125 prevented Bax/Bak-induced cell death in yeast and mammalian cells. ORFV125 also partially protected yeast from Bim-antagonism of Bcl-xL suppression of Bax-mediated yeast toxicity. To inhibit apoptosis, ORFV125 appears to interact with Bak/Bax which was manifested by co-immunoprecipitation. Although this study has accomplished that ORFV125 can block Bax/Bak function by binding, it is still not clear at which step ORFV125 inhibits Bax/Bak-induced death. Preliminary studies have demonstrated that ORFV125 restricts Bax activation at the early stages of mitochondrial apoptotic pathway whereby Bax is kept inactivated by ORFV125. It is probable this might affect Bax translocation to the mitochondria. Further studies need to be performed that might provide important information regarding the mechanisms of apoptotic death and the mechanisms that pathogens use to interfere with apoptosis.