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.
