Origin and Evolution of the Unique Hepatitis C Virus Circulating Recombinant Form 2k/1b

Abstract

Since its initial identification in St. Petersburg, Russia, the recombinant hepatitis C virus (HCV) 2k/1b has been isolated from several countries throughout Eurasia. The 2k/1b strain is the only recombinant HCV to have spread widely, raising questions about the epidemiological background in which it first appeared. In order to further understand the circumstances by which HCV recombinants might be formed and spread, we estimated the date of the recombination event that generated the 2k/1b strain using a Bayesian phylogenetic approach. Our study incorporates newly isolated 2k/1b strains from Amsterdam, The Netherlands, and has employed a hierarchical Bayesian framework to combine information from different genomic regions. We estimate that 2k/1b originated sometime between 1923 and 1956, substantially before the first detection of the strain in 1999. The timescale and the geographic spread of 2k/1b suggest that it originated in the former Soviet Union at about the time that the world's first centralized national blood transfusion and storage service was being established. We also reconstructed the epidemic history of 2k/1b using coalescent theory-based methods, matching patterns previously reported for other epidemic HCV subtypes. This study demonstrates the practicality of jointly estimating dates of recombination from flanking regions of the breakpoint and further illustrates that rare genetic-exchange events can be particularly informative about the underlying epidemiological processes. Hepatitis C virus (HCV) infection presents a major global health burden, with the WHO estimating that 170 million chronic carriers are at risk of developing severe clinical outcomes such as cirrhosis and hepatic cellular carcinoma (56, 71). The virus belongs to the single-stranded positive-sense RNA virus family Flaviviridae and is characterized by considerable genetic diversity. HCV diversity is classified into six main genotypes (genotypes 1 to 6), each of which is further divided into numerous subtypes, and the virus exhibits nucleotide sequence divergences of 30 and 20% at the genotype and subtype levels, respectively (58). The high genomic heterogeneity of HCV is a result of both its high rate of evolution and its long-term association with human populations (60). Although there is no indication for a zoonotic virus reservoir, a related virus has recently been discovered in dogs (22).The greatest diversity of HCV is found in West and Central Africa and in Southeast Asia, where the virus appears to have persisted endemically for at least several centuries (49, 60). The current distribution of HCV genotypes and subtypes is geographically structured, reflecting differences in the rates and routes of transmission of the various subtypes and genotypes. Epidemic strains, exemplified by subtypes 1a, 1b, and 3a, are characterized by high prevalence, low genetic diversity, and a global distribution and are typically associated with transmission via infected blood products and injecting drug use (IDU) during the 20th century (13, 4...

Do differences exist between chronic hepatitis C genotypes 2 and 3?

“…The hepatitis C virus (HCV) is characterized by genetic heterogeneity, which permits its classifi cation into distinct genotypes and subtypes by phylogenetic analysis 1 . This genetic diversity is related to the origin of the virus, its interesting evolution, its geographic and epidemiological pattern of dissemination, and its long persistence in humans 2,3 . Simmonds et al 1 proposed the classifi cation of HCV into six viral genotypes with several subtypes: 1 (1a, 1b, 1c), 2 (2a, 2b, 2c), 3 (3a, 3b), 4, 5 (5a), and 6.…”

Potential risk of misclassification HCV 2k/1b strains as HCV 2a/2c using VERSANT HCV Genotype 2.0 assay

“…The recombinant genotype 2k/1b was first described in St Petersburg in 2002 in intravenous (IV) drug users (Kalinina et al, 2002). Since its discovery, the genotype 2k/1b has been detected in many countries, including Ireland, Uzbekistan, Cyprus, France, the Netherlands, and Russia (Demetriou et al, 2009;Kalinina et al, 2002;Karchava et al, 2015;Kurbanov et al, 2008aKurbanov et al, , 2008bMoreau et al, 2006;Morel et al, 2010;Raghwani et al, 2012). In all these cases, the patients originated from Russia or Georgia.…”

“…In all these cases, the patients originated from Russia or Georgia. The recombinant genotype 2k/1b has a 5′ genome region that is most closely related to subtype 2k and a 3′ genome region that is most closely related to the global epidemic subtype 1b (Raghwani et al, 2012).…”

Commentary: Next-Generation Sequencing: a Diagnostic One-Stop Shop for Hepatitis C?

“…CRF1_2k/1b is currently the most prevalent HCV recombinant form. It has been reported in several countries worldwide-the countries of the former Soviet Union, Cyprus, France, the Netherlands, Belgium, and the United States (14)(15)(16)(17)(18)(19), and its prevalence is probably underestimated. Despite the fact that in comparison to human immunodeficiency virus (HIV), not many recombinant HCV forms have been identified so far, their reliable and timely recognition is crucial for selecting the optimal treatment regimen.…”