Host proteins involved in propagation and pathogenesis of Hepatitis C virus and other viruses of the family Flaviviridae
Seminar Room 2
Walter and Eliza Hall Institute
1g Royal Parade, Parkville
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Dr Okamoto’s current research is focused on the characterization of host factors involved in propagation and pathogenesis of hepatitis C virus (HCV) and other viruses belonging to the family of Flaviviridae. HCV core protein is the first viral protein to be translated from the HCV genome and it is cleaved by host cell derived signal peptide peptidase (SPP) to form a mature core protein.
Dr Okamoto has found that SPP is essential for HCV propagation and pathogenesis of HCV infection. In addition, SPP is also critical for protozoa including malaria and toxoplasma. These findings indicate that development of SPP inhibitors may be useful as anti-HCV and anti-malaria therapies. Dr Okamoto has also investigated the role of prosurvival Bcl-2 family proteins in the growth of flavivirus such as Japanese encephalitis virus (JEV), Dengue virus (DENV) and Zika virus (ZIKV). He has found that cells infected with JEV, DENV and ZIKV degraded Mcl-1 and inhibition of Bcl-xL suppressed propagation of flaviviruses in peripheral tissues. In addition, infection with Legionella bacteria and vaccinia virus and vesicular stomatitis virus had been also shown to degrade Mcl-1. These data suggest that Mcl-1 degradation is a common phenomenon in cells infected with intracellular pathogens.
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