Population genetic history of hepatitis C virus 1b infection in China

Abstract

Subtype 1b is the most common strain of Hepatitis C virus (HCV) in China. Here, the molecular epidemiology and epidemic history of this strain were investigated by conducting phylogenetic and population genetic analyses of E1 and NS5B gene sequences sampled from nine Chinese cities. The phylogenetic analysis indicated the presence of two clusters of Chinese strains that did not include reference strains from other countries, suggesting that these clusters represent two independent chains of HCV transmission within China. The remaining Chinese isolates were more closely related to reference strains from other countries. The date of origin and past population dynamics of the two groups were investigated using a new population genetic method, the Bayesian skyline plot. The estimated dates of origin of both groups coincide with the period of the Chinese 'Cultural Revolution' during the years [1966][1967][1968][1969][1970][1971][1972][1973][1974][1975][1976]. Both groups grew at a rapid exponential rate between~1970 and~1990, after which transmission slowed considerably. Possible explanations for the groups' fast spread and subsequent slowdown are discussed, including parenteral transmission by unsafe injection, iatrogenic transmission by infected blood or blood products and improvements in blood safety since 1990. These results shed light on HCV transmission in China and may help to predict the future burden of HCV-related disease in the country. INTRODUCTIONHepatitis C virus (HCV) is a genetically diverse RNA virus with a single-stranded, positive-sense genome. The virus is classified into six major genotypes with closely related isolates within each genotype being grouped into subtypes (Simmonds et al., 1993;Robertson et al., 1998). Partial genome sequences, particularly those from the E1 and NS5B genes, are commonly used in HCV genotyping and evolutionary analysis (e.g. Simmonds et al., 1993;Smith et al., 1997). Different HCV genotypes and subtypes have different geographical distributions, transmission routes and rates of spread (Bukh et al., 1993;Smith et al., 1997;Pybus et al., 2001). 'Epidemic' subtypes, such as 1a, 1b and 3a, are typically found at high prevalences globally having spread rapidly during the twentieth century, probably via infected blood, blood products and injecting drug use. In contrast, 'endemic' strains of HCV are usually less prevalent, found in restricted geographical areas and represent long-term, low-level endemic infection in particular populations Pybus et al., 2001).Evolutionary analysis of sampled virus sequences has advanced considerably during the past decade and is now an important tool in molecular epidemiology. In addition to standard phylogenetic analysis, population genetic methods based on coalescent theory can be used to estimate epidemiological history from viral gene sequences. Coalescent 3These authors contributed equally to this work. , 2003Tanaka et al., 2002Tanaka et al., , 2004Tanaka et al., , 2005Nakano et al., 2004).It has been estimated that 2?5-4?9 % of China's...

Evolutionary analysis of hepatitis C virus gene sequences from 1953

“…The phylogeny shows some spatial structure, with two well-supported clades containing the majority of the Chinese and Japanese sequences, as noted previously [27]. Several well-supported clades of US sequences are also evident.…”

Genetic History of Hepatitis C Virus in East Asia

“…However, such methods cannot be reliably applied to small data sets or short sequences. It is common for HCV molecular epidemiological surveys to produce short subgenomic fragments around 300 nt long, which by themselves are insufficient to reliably estimate phylogenetic groupings (34,52). The compromise solution used here was to increase statistical power by concatenating multiple subgenomic sequences, but at the expense of a reduction in the number of available reference strains for comparison.…”

The Current Hepatitis C Virus Prevalence in China May Have Resulted Mainly from an Officially Encouraged Plasma Campaign in the 1990s: a Coalescence Inference with Genetic Sequences

“…Before this study, the majority of the reports used two rates, 7.9 ϫ 10 Ϫ4 for E1 and 5.0 ϫ 10 Ϫ4 for NS5B, estimated based on the single-lineage-among-host 1b data sets (7). Although lower than those recently estimated (34,39), the two rates have been widely used for different HCV genotypes in various scenarios (5,8,18,33,40,41), and thus, they must also be applicable to this study. Based on such a premise, we may perform additional BEAST analyses for the 3a and 3b data sets using additional prior rates to obtain more time frames before selecting the most appropriate.…”

“…It correlates epidemic events and estimates historical population growth rates. It is powerful for performing retrospective analysis of the changes in effective population size using Bayesian skyline plots (BSPs), and this enables an easy display of the diverse histories from the most recent common ancestor (tMRCA) to the newest descendants (5,(16)(17)(18). Therefore, it has been widely used to estimate the past dynamics of HCV in various scenarios.…”