Functional and Phylogenetic Analysis of 5′ and 3′ Untranslated Regions (UTRs) of Hepatitis C Virus Genome (HCV) for the Potential Target Prediction of its Self- Regulation

Abstract

Hepatitis C virus (HCV) is an utmost communal well-being problem globally. Globally about 177.5 million individuals are tainted with HCV. Pakistan has second largest load of HCV with a country wide prevalence of 4.8 %. About 17 million mortal are tainted with HCV in Pakistan. Documenting the genetics of HCV has important implications for understanding disease severity as well in therapeutics. In this insilico study we conducted functional analysis of non coding 5’ and 3’ untranslated regions (UTRs) sequence of various HCV genotypes by multiple sequence alignment. Alongside we formulated and compared the secondary structures of these UTRs in Hepatitis C virus (HCV) of different regions and genotypes. RNA-RNA interaction was used to compare 5’ and 3’ non-coding UTRs with rest of coding viral genome using the most prevalent HCV-3a as model. Secondary structures of both UTRs regions were analyzed to confirm the structural stability and its involvement in self regulation of genes for survival and pathogenicity in the host. Lastly a phylogenetic analysis was constructed to determine homology and origin of HCV-3a virus in Pakistan. 5′ UTR sequence show high homology in Pakistan HCV-2a to HCV-3a sequence. The secondary structures of 5’ and 3’ UTRs of HCV-2a and HCV-3a of Pakistan showed significant structural differences and varying degree of stabilities in comparison to other countries i.e. India, Egypt, Us and Japan. In our study the 5’ UTR of HCV-3a Pakistan has less minimum free energies as compare to 3’ UTR of same genotypes. The interaction of non coding 5′ and 3′ UTR with ORF of HCV-3a Pakistan strain show 6-7 binding sites with low hybridization energies <-20 kcal/mol at core, E1, E2, NS2, NS4A, NS4B and NS5A. Phylogenetic analysis show that 5′ UTR HCV-2a Pakistan is closely related to US HCV-2a and 5′ UTR of HCV-3a Pakistan is closely related to that of 5′UTR of HCV-3a of India