A Genetic Analysis of Hepatitis C Virus Transmission between Injection Drug Users

Cochrane, Alexandra; Searle, Benjamin; Hardie, Alison; Robertson, Roy; Delahooke, Toby; Cameron, S.; Tedder, Richard S.; Dusheiko, G.; Lamballerie, Xavier de; Simmonds, Peter

doi:10.1086/344314

Cited by 62 publications

(64 citation statements)

References 27 publications

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“…2). The method for scoring is related to that used by the Association Index, a method developed previously to quantify the degree of segregation of different predefined groups (6,47).…”

Section: Resultsmentioning

confidence: 99%

Recombination in the Genesis and Evolution of Hepatitis B Virus Genotypes

Simmonds

Midgley

2005

J Virol

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Hepatitis B virus (HBV) infection is widely distributed in both human and ape populations throughout the world and is a major cause of human morbidity and mortality. HBV variants are currently classified into the human genotypes A to H and species-associated chimpanzee and gibbon/orangutan groups. To examine the role of recombination in the evolution of HBV, large-scale data retrieval and automated phylogenetic analysis (TreeOrder scanning) were carried out on all available published complete genome sequences of HBV. We detected a total of 24 phylogenetically independent potential recombinants (different genotype combinations or distinct breakpoints), eight of which were previously undescribed. Instances of intergenotype recombination were observed in all human and ape HBV variants, including evidence for a novel gibbon/genotype C recombinant among HBV variants from Vietnam. By recording sequence positions in trees generated from sequential fragments across the genome, violations of phylogeny between trees also provided evidence for frequent intragenotype recombination between members of genotypes A, D, F/H, and gibbon variants but not in B, C, or the Asian B/C recombinant group. In many cases, favored positions for both inter-and intragenotype recombination matched positions of phylogenetic reorganization between the human and ape genotypes, such as the end of the surface gene and the core gene, where sequence relationships between genotypes changed in the TreeOrder scan. These findings provide evidence for the occurrence of past, extensive recombination events in the evolutionary history of the currently classified genotypes of HBV and potentially in changes in its global epidemiology and associations with human disease.Infection with hepatitis B virus (HBV) is globally distributed, infecting approximately one-third of the world's human population. It is responsible for substantial proportion of liver disease that kills over one million people through uncompensated liver disease or hepatocellular carcinoma each year (43). Populations in South and East Asia, sub-Saharan Africa, and Central and South America show particularly high frequencies of HBV infection that may be maintained through mother-tochild perinatal transmission (13) or horizontal transmission in childhood (8,41).HBV variants infecting humans show genetic and antigenic heterogeneity and are currently classified into seven or eight genotypes that differ from each other in nucleotide sequence by 10 to 13% (29-31, 33). While genotypes A, D, and possibly G have global distributions, genotypes B and C are found predominantly in East and Southeast Asia, genotype E is found in West Africa, and genotypes F and H are found among various population groups, including indigenous peoples in Central and South America. Active and resolved HBV infections are also found at high frequencies in chimpanzees (17,17,24,42,45) and Southeast Asian apes (12,28,46,49) with species-associated HBV variants distinct from those found in human populations. Finally, an HBV varia...

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“…2). The method for scoring is related to that used by the Association Index, a method developed previously to quantify the degree of segregation of different predefined groups (6,47).…”

Section: Resultsmentioning

confidence: 99%

Recombination in the Genesis and Evolution of Hepatitis B Virus Genotypes

Simmonds

Midgley

2005

J Virol

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214

255

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“…The introduction of such strains may arise through travel or immigration (Bernier et al, 1996;Morice et al, 2001;Stuyver et al, 1995), by the import and export of contaminated blood products (Kinoshita et al, 1993) or through networks of injecting drug users (Cochrane et al, 2002). It is interesting to note that the two transmission patterns described above have also recently been noted for another virus; in an analysis of HIV-1 subtype B in the UK, Hue et al (2005) found at least six co-circulating transmission clusters within a single risk group.…”

Section: Discussionmentioning

confidence: 98%

“…The second pattern is represented by the individual Chinese isolates of HCV that are more closely related to non-Chinese isolates of HCV, which most likely represent multiple, sporadic migration of strains of HCV. We tried to investigate which countries these sporadic strains were derived from but our phylogenies were insufficiently resolved to answer this question reliably (data not shown).The introduction of such strains may arise through travel or immigration (Bernier et al, 1996;Morice et al, 2001;Stuyver et al, 1995), by the import and export of contaminated blood products (Kinoshita et al, 1993) or through networks of injecting drug users (Cochrane et al, 2002). It is interesting to note that the two transmission patterns described above have also recently been noted for another virus; in an analysis of HIV-1 subtype B in the UK, Hue et al (2005) found at least six co-circulating transmission clusters within a single risk group.…”

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confidence: 99%

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

Nakano

Lü

et al. 2006

Journal of General Virology

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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...

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“…A disadvantage of this study type is that transmission inference is based on phylogenetic data derived from strains of long-standing infection combined with information on current injecting partners, similar to the contemporaneous residential data used in the current study. Other investigators have taken phylogenetic clustering outcome as direct evidence of individual membership in a contact network (34)(35)(36)(37)(38).…”

Section: Gt3mentioning

confidence: 99%

Spatiotemporal Reconstruction of the Introduction of Hepatitis C Virus into Scotland and Its Subsequent Regional Transmission

McNaughton

Cameron

Wignall-Fleming

et al. 2015

J Virol

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A more comprehensive understanding of hepatitis C virus (HCV) transmission dynamics could facilitate public health initiatives to reduce the prevalence of HCV in people who inject drugs. We aimed to determine how HCV sequences entered and spread throughout Scotland and to identify transmission hot spots. A Scottish data set with embedded demographic data was created by sequencing the NS5B of 125 genotype 1a (Gt1a) samples and 166 Gt3a samples and analyzed alongside sequences from public databases. Applying Bayesian inference methods, we reconstructed the global origin and local spatiotemporal dissemination of HCV in Scotland. Scottish sequences mainly formed discrete clusters interspersed between sequences from the rest of the world; the most recent common ancestors of these clusters dated to 1942 to 1952 (Gt1a) and 1926 to 1942 (Gt3a), coincident with global diversification and distribution. Extant Scottish sequences originated in Edinburgh (Gt1a) and Glasgow (Gt3a) in the 1970s, but both genotypes spread from Glasgow to other regions. The dominant Gt1a strain differed between Edinburgh (cluster 2 [C2]), Glasgow (C3), and Aberdeen (C4), whereas significant Gt3a strain specificity occurred only in Aberdeen. Specific clusters initially formed separate transmission zones in Glasgow that subsequently overlapped, occasioning city-wide cocirculation. Transmission hot spots were detected with 45% of samples from patients residing in just 9 of Glasgow's 57 postcode districts. HCV was introduced into Scotland in the 1940s, concomitant with its worldwide dispersal likely arising from global-scale historical events. Cluster-specific transmission hubs were identified in Glasgow, the key Scottish city implicated in HCV dissemination. This fine-scale spatiotemporal reconstruction improves understanding of HCV transmission dynamics in Scotland. IMPORTANCEHCV is a major health burden and the leading cause of hepatocellular carcinoma. Public health needle exchange and "treatment as prevention" strategies targeting HCV are designed to reduce prevalence of the virus in people who inject drugs (PWID), potentially mitigating the future burden of HCV-associated liver disease. Understanding HCV transmission dynamics could increase the effectiveness of such public health initiatives by identifying and targeting regions playing a central role in virus dispersal. In this study, we examined HCV transmission in Scotland by analyzing the genetic relatedness of strains from PWID alongside data inferring the year individuals became infected and residential information at a geographically finer-scale resolution than in previous studies. Clusters of Scotland-specific strains were identified with regional specificity, and mapping the spread of HCV allowed the identification of key areas central to HCV transmission in Scotland. This research provides a basis for identifying HCV transmission hot spots. H epatitis C virus (HCV) currently infects an estimated 180 million people throughout the world. Following a short acute phase, the virus ...

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A Genetic Analysis of Hepatitis C Virus Transmission between Injection Drug Users

Cited by 62 publications

References 27 publications

Recombination in the Genesis and Evolution of Hepatitis B Virus Genotypes

Recombination in the Genesis and Evolution of Hepatitis B Virus Genotypes

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

Spatiotemporal Reconstruction of the Introduction of Hepatitis C Virus into Scotland and Its Subsequent Regional Transmission

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