The hepatitis C virus (HCV), which currently infects an estimated 3% of people worldwide, has been present in some human populations for several centuries, notably HCV genotypes 1 and 2 in West Africa and genotype 6 in Southeast Asia. Here we use newly developed methods of sequence analysis to conduct the first comprehensive investigation of the epidemic and evolutionary history of HCV in Asia. Our analysis includes new HCV core (n ‫؍‬ 16) and NS5B (n ‫؍‬ 14) gene sequences, obtained from serum samples of jaundiced patients from Laos. These exceptionally diverse isolates were analyzed in conjunction with all available reference strains using phylogenetic and Bayesian coalescent methods. We performed statistical tests of phylogeographic structure and applied a recently developed "relaxed molecular clock" approach to HCV for the first time, which indicated an unexpectedly high degree of rate variation. Our results reveal a >1,000-year-long development of genotype 6 in Asia, characterized by substantial phylogeographic structure and two distinct phases of epidemic history, before and during the 20th century. We conclude that HCV lineages representing preexisting and spatially restricted strains were involved in multiple, independent local epidemics during the 20th century. Our analysis explains the generation and maintenance of HCV diversity in Asia and could provide a template for further investigations of HCV spread in other regions.

Understanding the origin and nature of hepatitis C virus (HCV) genetic diversity is critical for improving treatment and vaccine design, and such diversity is the sole source of information about the virus' epidemic history prior to its identification 20 years ago. In this paper, we study the molecular epidemiology of HCV genotype 2 in its region of endemic origin, west and central Africa. Our analysis includes 56 new and highly diverse HCV isolates sampled from infected individuals in Guinea-Bissau. By combining phylogenetic, geographical and epidemiological information, we find a previously unappreciated geographical structure in the diversity of HCV genotype 2, pointing to a history of eastwards spatial spread from the west African coast to Cameroon that took place over several centuries. Molecular clock analysis dates the common ancestor of HCV in Guinea-Bissau to 1470 (1414-1582). The phylogenetic position of isolates from Madagascar and Martinique suggests a role for the historical slave trade in the global dissemination of HCV and of the epidemic subtypes 2a and 2c. Coalescent-based estimates of epidemic growth indicate a rapid 20th-century spread of HCV genotype 2 in Cameroon that is absent in Guinea-Bissau. We discuss this contrast in the context of possible parenteral HCV exposure during public-health campaigns undertaken during the colonial era.

g Evolutionary analysis of hepatitis C virus (HCV) genome sequences has provided insights into the epidemic history and transmission of this widespread human pathogen. Here we report an exceptionally diverse set of 178 HCV genotype 2 (HCV-2) isolates from 189 patients in Amsterdam, comprising 8 distinct HCV subtypes and 10 previously not recognized, unclassified lineages. By combining study subjects' demographic information with phylogeographic and molecular clock analyses, we demonstrate for the first time that the trans-Atlantic slave trade and colonial history were the driving forces behind the global dissemination of HCV-2. We detect multiple HCV-2 movements from present-day Ghana/Benin to the Caribbean during the peak years of the slave trade (1700 to 1850) and extensive transfer of HCV-2 among the Netherlands and its former colonies Indonesia and Surinam over the last 150 years. The latter coincides with the bidirectional migration of Javanese workers between Indonesia and Surinam and subsequent immigration to the Netherlands. In addition, our study sheds light on contemporary trends in HCV transmission within the Netherlands. We observe multiple lineages of the epidemic subtypes 2a, 2b, and 2c (together 67% of HCV-2 infections in Amsterdam), which cluster according to their suspected routes of transmission, specifically, injecting drug use (IDU) and contaminated blood/blood products. Understanding the epidemiological processes that generated the global pattern of HCV diversity seen today is critical for exposing associations between populations, risk factors, and specific HCV subtypes and might help HCV screening and prevention campaigns to minimize the future burden of HCV-related liver disease.

No abstract

No abstract