|Hepatitis induced by HCV and HCV-HIV co-infection|
Hepatitis C is a major health problem in India with nearly 15 million affected subjects. We intend to employ pharmacogenomics approach to define the likely genotype based host proteins and viral sequences which may be responsible for high immunogenicity of HCV. Recent human genome-wide association studies (GWAS) revealed a strong association between IL28B gene variation and the treatment response in chronic hepatitis C patients, Our data of single nucleotide polymorphisms (SNP), rs8103142 located in the IL28B gene in our Indian population in genotype 3 and found genetic polymorphism near the IL28B gene ,encoding interferon-l-3 (IFN- l-3), is associated with response to treatment.
To understand the mechanisms by which HCV interacts with host, we are developing in vitro culture model system by cloning the full length HCV genotype 3 and also identifying novel host proteins which interact with E1 and E2 and play a role in virus assembly and release. These host proteins would serve as novel targets to develop effective antiviral therapeutics to treat HCV. In HCV immune biology in chronic patients, our data show that both T-cells and dendritic cells (DCs) were found to be dysfunctional in HCV treatment naive patients and Peg-IFN and ribavirin therapy helps in restoring the immunity in these patients working both at the level of T-cells and DCs. However, in HCV-HIV coinfection, our data indicate dysregulation of the immune system following reduction in the effector memory T-cell population & increase in naïve population during co-infection may contribute to reduced antiviral response. Also, increased expression of inhibitory molecules on the T-cells during coinfection may result in skewing of T-cells towards exhaustion.