Journal
VIROLOGY
Volume 329, Issue 1, Pages 53-67Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2004.08.012
Keywords
hepatitis C virus; apoptosis; caspase-8; flavivirus
Categories
Ask authors/readers for more resources
Apoptosis has been implicated in the pathogenesis of hepatitis C virus (HCV)-related disease. Here, we show that expression of HCV NS3, or the NS2/NS3 precursor protein, in mammalian cells results in induction of apoptosis and activation of caspases. HCV NS3-induced apoptosis was blocked by a caspase-8, but not a caspase-9-specific inhibitor. HCV NS3 coimmunoprecipitated with caspase-8, but not with other caspases or with FADD. Coexpression of HCV NS3 and caspase-8 resulted in aggregation of the caspase in punctate structures that colocalized with HCV NS3. Cell lines stably expressing low levels HCV NS3 showed increased sensitivity to Fas-induced cell death. Point mutations of NS3 showed that the pro-apoptotic function of the protein is distinct from its protease and helicase activities. These findings suggest that HCV NS3 promotes caspase-8 induced apoptosis at a pathway site distal to FADD, and that flavivirus NS3 may represent a new class of pro-apoptotic proteins. Published by Elsevier Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available