Vaccine and Infectious Disease Division

The function of viral core protein during acute Hepatitis C Virus infection

Hepatitis C is an infectious disease of the liver caused by the Hepatitis C Virus (HCV).  Initial infection is often asymptomatic and occasionally self-resolves, but about 85% of cases result in chronic disease that can progress to cirrhosis or liver cancer.  During chronic infection, the core protein from HCV is known to be important in evading immune responses by disrupting host signaling pathways, including innate inflammatory and antiviral responses.  Studies have found that the sequence of core differs between viruses isolated from early and advanced liver disease, and between liver tumor and non-tumor tissue, suggesting that the functions of core might differ between, and potentially be responsible for, each of these disease states.  Comparably little is known about the function of core during initial infection, and whether differences in the sequence or function of core might be responsible for establishing chronic infection.

In an effort to better understand the role of core during initial Hepatitis C infection, VIDI affiliate investigator Dr. Stephen J. Polyak and colleagues isolated and analyzed the protein from 13 recently infected Hepatitis C patients.  They found a variety of sequence differences among the samples, some of which had not previously been observed in samples from patients with chronic HCV infection.  The researchers then put these isolated core genes into cell lines grown in the laboratory, and through a series of assays looking at subcellular localization, secretion of core from the cells, and the protein’s ability to perturb host innate inflammatory and antiviral responses, found that all of the observed variants of core taken from patients with acute HCV infection were functional and behaved similarly to core from patients with chronic infection.  Taken together, these findings indicate that the previously known functions of core are present during early HCV infection, but the newly discovered sequence differences will be interesting to study in more detail to determine if they play a role in establishing chronic infection.

Functional characterization of core genes from patients with acute hepatitis C virus infection. Tang X, Wagoner J, Negash A, Austin M, McLauchlan J, Hahn YS, Rosen HR, Polyak SJ. J Infect Dis. 2010 Mar 15;201(6):912-22