Mutations in ISDR may be linked to high viremia and virus resistance to IFN-alpha-2b but responsive to PEG-IFN-alpha-2a

Abstract

Mutation in interferon sensitivity determining region may play role in virus resistance. Genotype 3a patient was subjected to 48 weeks combination therapy of IFN-alpha-2b plus ribavirin but he showed high levels of viremia before, during and after treatment although his ALT level became normal. His IL-8 and TNF-alpha levels werefound quite high before and after IFN-alpha-2 combination therapy. While comparing its ISDR-NS5A with end of

treatment responder patient, eight mutations were observed in a 52 amino acid protein residue. Patient was advised for PEG-IFN-alpha-2a combination therapy for 24 weeks, to which he responded well after 4 week and showed sustained virologic response after 06 months of completion of therapy. His IL-8 and TNF-alpha levels also came to lower levels after treatment with PEG-IFN-alpha 2a combination therapy. In phylogenetic tree its genome (NZ1) along with another nonresponder case (NZ2) was placed close to Brazilian isolates. NZI and NZ2 showed 87 % sequence homology with each other while NZ1 had 89% sequence homology with EF208017 and 87% with EF20995. NZ2 showed 91% homology with EF208017 and 98% with EF207995 which is quite interesting. Mutations in ISDR sequence may be the reason for non response to IFN combination therapy of this HCV genotype 3 patient. ISDR of genotype 3 along with IL-8 and TNF-alpha may be screened on larger scale in Pakistani population which may help in deciding a cost effective treatment plan.