UC San Diego

Hepatitis C Virus (HCV) is a blood-borne virus found worldwide, though most prevalent in third world countries. Currently, there is no vaccine and chronic infection can lead to hepatocellular carcinoma and liver cirrhosis. Our lab has shown upon HCV infection there is an increase in phosphorylated IκBα (p-IκBα) at five days post infection. This is a surprising as p-IκBα is canonically degraded by the 26S proteasome during activation of the NFκB pathway. In this dissertation, we corroborate that HCV infection does increase p-IκBα at five days post infection, but in addition, discovered p-IκBα locates to the nucleus. This is interesting as p-IκBα is canonically not found in the nucleus. To elucidate what viral protein is responsible for this phenomenon the mature and immature version of the capsid protein, also known as core, were analyzed due to its ability to interact with host pathways. We discovered not only does the presence of mature version increase the expression of p-IκBα in the nucleus, but it also physically interacts with it. Taken together, these events could be an important part of the viral life cycle, and is a promising possible target for therapeutics.