HCV Core Genotype-1b
Description
Product Specs
Product Science Overview
Hepatitis C Virus (HCV) is a significant global health concern, affecting over 150 million people worldwide. It is a major cause of chronic liver diseases, including cirrhosis and hepatocellular carcinoma. HCV is classified into seven genotypes, with numerous subtypes that respond differently to antiviral therapies. Among these, Genotype 1, particularly subtype 1b, is the most prevalent genotype globally .
HCV is a single-stranded positive-sense RNA virus. Its genome encodes a single polyprotein, which is processed into at least 11 polypeptides/proteins. These include three structural proteins (core, and envelope proteins E1 and E2), a small polypeptide named p7, the novel F protein, and six nonstructural (NS) proteins (NS2, NS3, NS4A, NS4B, NS5A, and NS5B) .
The development of recombinant HCV infectious cell culture systems has been a significant advancement in the field. These systems allow for the efficacy and resistance testing of antiviral drugs. The high replication capacity of strain JFH1 (genotype 2a) has been instrumental in this development. However, efficient infectious JFH1-based cell cultures of subtype 1b have been limited and typically comprise only the 5′ untranslated region (5′UTR)-NS2, NS4A, or NS5A regions .
Researchers have developed efficient infectious JFH1-based cultures with genotype 1b core-NS5A sequences of strains DH1, Con1, and J4. These cultures were created using previously identified HCV cell culture adaptive substitutions A1226G, R1496L, and Q1773H. These viruses spread efficiently in Huh7.5 cells by acquiring additional adaptive substitutions, and final recombinants yielded peak supernatant infectivity titers of 4 to 5 log 10 focus-forming units (FFU)/ml .
The developed HCV genotype 1b culture systems are valuable tools for assessing the efficacy of various classes of antivirals. They are also crucial for other virological studies requiring genotype 1b infectious viruses. The inhibitors tested against these novel genotype 1b viruses, as well as against previously developed 1a viruses, showed that NS5A inhibitors had half-maximal effective concentrations several orders of magnitude lower than NS3/4A protease inhibitors .
