Phylogenomics of Hepatitis C Virus and Evaluation of Host Immune Factors under Different Treatment Regimes

Abstract

Hepatitis C Virus (HCV) infection is a serious health concern, with baleful socio-economical consequences. Current investigation focused on HCV diagnostics and immune regulation under different treatment options. HCV genome was analyzed using a simple genome analysis approach based on extensive phylogenomics and new genomic locations on NS3, NS4A and NS4B were identified for HCV genotyping. Grounded on these novel identified locations, a PCR based HCV genotyping assay was designed with enhanced specificity towards Pakistani isolates. IFNL3 polymorphism has been strongly associated with interferon/ribavirin treatment outcome in HCV genotypes 1 and 4 infected patients while conflicting results have been reported for genotypes 2 and 3. Thus in current study, predictive value of five IFNL3 SNPs with treatment outcome was investigated in genotype 3 patients. IFNL3 SNPs showed no association with sustained virological response (SVR) following treatment, either individually or in haplotype, indicating that genotyping IFNL3 SNPs have limited predictive value in HCV patients with genotype 3. Immune system regulation during HCV infection and under different treatment options is poorly apprehended. The role of selected host immune regulatory factors – IL7, IL11, IL15, IL27, FAM26F & IDO, under different treatment regimes was investigated by measuring their differential expression in peripheral blood mononuclear cell. Results of the expression studies of immune regulatory factors herein indicated that HCV infection modulates host immune regulatory factors to decrease T-cell and NK cellular activity. These finding are important in the context that T-cell and a specific NK cellular activity is required for clearance of viral infections. Following treatment, especially Sofosbuvir and peg-interferon the immune system tries to restore lost T-cell and NK cellular activity by modulating these host regulatory factors to combat the infection. In conclusion, current study has identified a more relevant genotyping assay for HCV genotyping and the relevance of IFNL3 SNPs with treatment outcome as well as the role of various immune modulators in dictating the treatment outcomes.