Abstract

Hepatitis C Virus (HCV) is the most prevalent human pathogen in Pakistan and is the major cause of liver cirrhosis and hepatocellular carcinoma in infected patients. It has shifted from being hypo-endemic to being hyper-endemic. There was no information about the origin and evolution of the local variants. Here we use newly developed phyloinformatic methods of sequence analysis to conduct the first comprehensive investigation of the evolutionary and biogeographic history in unprecedented detail and breadth. Considering evolutionary rate and molecular-clock hypothesis in context, we reconstructed the spatiotemporal spread of HCV in the whole territory of its circulation using a combination of Bayesian MCMC methods utilizing all sequences available in GenBank. Comparative analysis were performed and were addressed. Whole genome and individual gene analysis have shown that sub-types 1a, 1b and 3a are recognized as epidemic strains and are distributed globally. Here we confirm that the origin of HCV 3a genotypes is in South Asia and HCV has evolved in the region to become stably adapted to the host environment.

Highlights

  • Hepatitis C virus (HCV) is a pandemic human virus

  • The maximum likelihood (ML) phylogenetic analysis of NS5B gene S1 Table showed that HCV genotypes 1a origin in Pakistan is polyphyletic and has occurred due to multiple outbreaks at different points in time

  • The results revealed that HCV genotype 3a is the most diverse genotype in Pakistan

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Summary

Introduction

Hepatitis C virus (HCV) is a pandemic human virus. It’s a leading cause of chronic liver diseases including hepatocellular carcinoma and liver cirrhosis. Worldwide about 200 million people are infected with the virus. 3–4 million people are diagnosed with new infections annually [1]. In Pakistan, almost 10 million people i.e. 6% of its population are reported to be infected with the virus[2]. HCV is a blood-borne pathogen and the main cause of virus transmission is a blood transfusion. Other risk factors include medical and dental procedures with unsterilized equipment, hemodialysis, organ transplants from HCV-infected patients, needle injuries, piercing and tattooing in unhygienic circumstances and intravenous drug usage

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