Virology & Mycology
Open Access

Abstract

Current Challenges in Hepatitis C Virus

Abhishek S and Gadepalli R

HCV is an enveloped, positive-strand RNA virus and belongs to the genus Hepacivirus within the family Flaviviridae. Hepatitis C virus is characterized by a high genomic diversity resulting from the high mutation rate . The genome of this virus is approximately 9.6 Kb long and encodes a single poly-protein. The encoded poly-protein is co- and post-translationally processed to produce a total of 10 viral proteins by both viral and host proteases (N terminus-Core-E1-E2-p7-NS2-NS3-NS4A-NS4B-NS5A-NS5B-C terminus). The structural proteins at the N terminus (Core, E1 and E2) are directly involved in the formation of new virions while the rest are non-structural protein involved in various aspects of HCV life cycle. P7 protein is known as an ion channel protein (Viroporin) and NS2 protein is a cysteine autoproteases catalysing the cleavage between NS2 and NS3 protein. Both p7 and NS2 proteins are also known to involve in virus assembly. NS3 to NS5B (NS3-NS4A-NS4B-NS5A-NS5B) are indispensable for viral RNA replication as the major component of the replication complex. NS3 protein has both serine protease and helicase activity. Protease activity cleaves the viral protein from NS3 to NS5B while helicase activity plays an important role in viral assembly. NS4A protein is co-factor of NS3 protein. NS4B provides the platform for the viral RNA replication to occur by generating membranous web structures near the ER membrane of the host cell. NS5A protein does not have any known enzymatic activity but is important for both RNA replication and assembly. Finally NS5B protein is an RNA dependent RNA polymerase synthesizing plus- and minus-strand of viral RNA. Amongst these NS3, NS5A and NS5B proteins are the major targets of currently available Direct-acting Antiviral agents (DAAs).