Key result
Culture-adaptive HCV core mutants (K23E and V31A) demonstrated enhanced RNA replication and attenuated TBK1-mediated activation of interferon-related promoters compared to the parental virus.
HCV core mutations K23E and V31A attenuate cellular antiviral activity by modulating type I interferon pathways, suggesting a mechanism for establishing persistent infection.
HCV core mutations may promote persistence via interferon attenuation; hypothesis-generating in animal models, human validation required.
Hepatitis C virus (HCV) often establishes a persistent infection that leads to chronic liver diseases. The viral core protein modulates various cellular activities involved in this process. We found two mutations, K23E and V31A, in the core gene of the transfected HCV JFH-1 genome, which had been replicated for a prolonged period. The mutant viruses escaped immunochemical detection by a core-specific antibody and demonstrated enhanced RNA replication and protein expression, compared to the parental virus. The mutant core proteins bound less tightly than the parental type core to the DEAD-box RNA helicase DDX3 and attenuated the TBK1-mediated activation of interferon-related promoters. These results suggest a mechanism by which the viruses adapt to attenuate cellular antiviral activity and to establish persistent infection.
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Kang et al. (2012) studied Hepatitis C virus infection. HCV core mutants (K23E and V31A) vs. Parental type core virus was evaluated on RNA replication, protein expression, and TBK1-mediated activation of interferon-related promoters. Culture-adaptive HCV core mutants (K23E and V31A) demonstrated enhanced RNA replication and attenuated TBK1-mediated activation of interferon-related promoters compared to the parental virus.
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