The Role of NS5A in Chronic HCV Infection

Simkins, Allison

Publication

The Role of NS5A in Chronic HCV Infection

Simkins, Allison

Date

2015

Additional date(s)

2015-05-01

Abstract

Hepatitis C is a viral disease that affects the liver cells of the infected individual, resulting in inflammation and frequent liver failure. Currently 150-200 million people worldwide are infected with Hepatitis C and 85% of these incidences have developed into a chronic condition. The causative agent for Hepatitis C is HCV (hepatitis C virus): an enveloped, positive single-stranded RNA virus, and a member of the Flaviviridae family. The RNA genome possesses ten structural and nonstructural proteins, notably Nonstructural Protein 5A (NS5A), the center of our research. When HCV infects the host, a downstream activation of the antiviral response produces type I interferons and proinflammatory cytokines. By an unknown process, NS5A possesses the capability of inhibiting the expression of IFN-beta. The goal of this project was to characterize the inhibition of the signaling pathway leading to antiviral gene expression. To better understand this interaction, we used a commercially available NS5A inhibitor, Daclatasvir, in combination with a mutant of NS5A, NS5A-10A, known to inhibit the IFN-beta promoter. As expected, we observed a reduction in IFN-beta expression in the presence of a mutated NS5A-10A. The level of IFN-beta expression increased when Daclatasvir was added, validating the observation that NS5A is capable of inhibiting IFN-beta gene expression.