title: Origin of hepatitis C virus genotype 3 in Africa as estimated through an evolutionary analysis of the full-length genomes of nine subtypes, including the newly sequenced 3d and 3e.
abstract: We characterized the full-length genomes of nine hepatitis C virus genotype 3 (HCV-3) isolates: QC7, QC8, QC9, QC10, QC34, QC88, NE145, NE274 and 811. To the best of our knowledge, NE274 and NE145 were the first full-length genomes for confirming the provisionally assigned subtypes 3d and 3e, respectively, whereas 811 represented the first HCV-3 isolate that had its extreme 3' UTR terminus sequenced. Based on these full-length genomes, together with 42 references representing eight assigned subtypes and an unclassified variant of HCV-3, and 10 sequences of six other genotypes, a timescaled phylogenetic tree was reconstructed after an evolutionary analysis using a coalescent Bayesian procedure. The results indicated that subtypes 3a, 3d and 3e formed a subset with a common ancestor dated to ~202.89 [95% highest posterior density (HPD): 160.11, 264.6] years ago. The analysis of all of the HCV-3 sequences as a single lineage resulted in the dating of the divergence time to ~457.81 (95% HPD: 350.62, 587.53) years ago, whereas the common ancestor of all of the seven HCV genotypes dated to ~780.86 (95% HPD: 592.15, 1021.34) years ago. As subtype 3h and the unclassified variant were relatives, and represented the oldest HCV-3 lineages with origins in Africa and the Middle East, these findings may indicate the ancestral origin of HCV-3 in Africa. We speculate that the ancestral HCV-3 strains may have been brought to South Asia from Africa by land and/or across the sea to result in its indigenous circulation in that region. The spread was estimated to have occurred in the era after Vasco da Gama had completed his expeditions by sailing along the eastern coast of Africa to India. However, before this era, Arabians had practised slave trading from Africa to the Middle East and South Asia for centuries, which may have mediated the earliest spread of HCV-3.
authors.affiliation: Center for Viral Oncology, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Li
authors.affiliation: Center for Viral Oncology, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
authors.affiliation: Institut national de santé publique du Québec, Laboratoire de santé publique du Québec, Sainte-Anne-de-Bellevue, QC, Canada.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Murphy
authors.affiliation: Divisions of Gastroenterology and Hepatology and of Clinical pathology, University Hospitals, Geneva, Switzerland.
authors.forename: Francesco
authors.initials: F
authors.lastname: Negro
authors.affiliation: Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi 329-0498, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okamoto
mesh_terms: D000349:Africa / Q000453:epidemiology; D016000:Cluster Analysis; D019143:Evolution, Molecular; D016679:Genome, Viral; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006526:Hepatitis C / Q000453:epidemiology* / Q000821:virology*; D006801:Humans; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D012367:RNA, Viral