Abstract

Hepatitis C virus (HCV) genotype and subtype distribution differs according to geographic origin and transmission risk category. Previous molecular epidemiology studies suggest the presence of multiple subtypes among Cypriot subjects. To investigate HCV genotype- and subtype-specific dissemination patterns, origins, and transmission in Cyprus, we analyzed HCV sequences encoding partial Core-E1 and NS5B regions. Analyzed populations comprised the general population and high-risk cohorts in Cyprus and a globally sampled dataset. Maximum-likelihood phylogeny reconstruction with bootstrap evaluation, character reconstruction using parsimony, and bootstrap trees estimated by ML were performed to identify the geographic origin of HCV subtypes and statistically significant dispersal pathways among geographic regions. Phylogeographic analyses traced the origin of subtypes in the general population and among PWID in Cyprus to unique and overlapping globally distributed regions. Phylogenetic analysis in Core-E1 revealed that most sequences from incarcerated populations in Cyprus clustered with the general population and PWID. We estimate that HCV infections in Cyprus originate from multiple global sources while most HCV transmissions among incarcerated individuals occur locally. This analysis is one of a few studies tracing HCV dispersal patterns using global datasets, and these practices and findings should inform how HCV epidemics are targeted by future prevention policies.

Highlights

  • Previous estimates reported that genotype 1 was the most prevalent (46.2%), followed by 3a (30.1%)[5]

  • Hepatitis C virus (HCV) dispersal for the most prevalent subtypes (1a, 1b, and 3a) in Cyprus were estimated by means of statistical phylogeographic analysis using globally sampled HCV sequences as references

  • Inferences about the origin of HCV transmission events were based on estimations of the number of viral mobility events between sampled locations

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Summary

Introduction

Previous estimates reported that genotype 1 was the most prevalent (46.2%), followed by 3a (30.1%)[5]. For people who inject drugs, the 2k/1b recombinant type that has been previously described in Russia was detected[6].The global distribution of subtypes 1a and 1b has likely been shaped by the dissemination of blood and blood products after the Second World War[7], while the distribution of genotype 3 is likely a result of the mobility of PWID and drug trafficking[8,9,10]. In Cyprus, HCV infection from intravenous drug use is associated with each prevalent subtype[11]. With these transmission mechanisms, local and global human movement primarily drive the phylogeography of HCV due to the evolutionary dynamics of the virus[12]. Phylogeographic analysis, which has been underutilized to studies of trends of HCV distribution and dissemination patterns, is an applicable tool to assess these topics

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