title: Genetic history of hepatitis C virus in Pakistan.
abstract: Hepatitis C virus (HCV) genotype 3a accounts for ∼80% of HCV infections in Pakistan, where ∼10 million people are HCV-infected. Here, we report analysis of the genetic heterogeneity of HCV NS3 and NS5b subgenomic regions from genotype 3a variants obtained from Pakistan. Phylogenetic analyses showed that Pakistani genotype 3a variants were as genetically diverse as global variants, with extensive intermixing. Bayesian estimates showed that the most recent ancestor for genotype 3a in Pakistan was last extant in ∼1896-1914 C.E. (range: 1851-1932). This genotype experienced a population expansion starting from ∼1905 to ∼1970 after which the effective population leveled. Death/birth models suggest that HCV 3a has reached saturating diversity with decreasing turnover rate and positive extinction. Taken together, these observations are consistent with a long and complex history of HCV 3a infection in Pakistan.
authors.affiliation: National Centre of Excellence in Molecular Biology, Division of Molecular Virology and Molecular Diagnostics, University of the Punjab, Genome Center for Molecular Diagnosis & Research, Lahore, Pakistan.
authors.forename: Irshad
authors.initials: I
authors.lastname: ur Rehman
authors.affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: GVaughan@cdc.gov.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Vaughan
authors.affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Purdy
authors.affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Guo-liang
authors.initials: GL
authors.lastname: Xia
authors.affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Forbi
authors.affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA; Department of Biology, Institute of Bioscience, Language and Exact Science, São Paulo State University, São José do Rio Preto, SP, Brazil.
authors.forename: Livia Maria Gonçalves
authors.initials: LM
authors.lastname: Rossi
authors.affiliation: National Centre of Excellence in Molecular Biology, Division of Molecular Virology and Molecular Diagnostics, University of the Punjab, Genome Center for Molecular Diagnosis & Research, Lahore, Pakistan.
authors.forename: Sadia
authors.initials: S
authors.lastname: Butt
authors.affiliation: National Centre of Excellence in Molecular Biology, Division of Molecular Virology and Molecular Diagnostics, University of the Punjab, Genome Center for Molecular Diagnosis & Research, Lahore, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Idrees
authors.affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Yury E
authors.initials: YE
authors.lastname: Khudyakov
mesh_terms: D001499:Bayes Theorem; D019143:Evolution, Molecular; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D010154:Pakistan / Q000453:epidemiology; D010802:Phylogeny; D017361:Viral Nonstructural Proteins; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
chemical_list: D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: Genetic diversity; Hepatitis C Virus; Pakistan