HCV Phylogeography of the General Population and High-Risk Groups in Cyprus Identifies the Island as a Global Sink for and Source of Infection.

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.

Spatiotemporal Characteristics of the HIV-1 CRF02_AG/CRF63_02A1 Epidemic in Russia and Central Asia.

Eastern European countries, including Russia, Ukraine, and other former Soviet Union (FSU) countries, have experienced a human immunodeficiency virus (HIV) epidemic spreading mostly among people who inject drugs (PWID). We aimed to investigate the origin and the dispersal patterns of HIV-1 CRF02_AG in Russia and other FSU countries. We studied 136 CRF02_AG sequences originating from Russia, and FSU countries along with a globally sampled dataset of 3,580 CRF02_AG sequences. Maximum-likelihood phylogeny reconstruction with bootstrap evaluation was conducted in RAxML. Bayesian phylogeographic analysis was performed in BEAST v1.8 using the discrete trait model. We found that all CRF02_AG sequences from Russia and other FSU countries formed a single monophyletic cluster within CRF02_AG radiation. The Russian/FSU clade was classified as CRF63_02A1. Sequences from the FSU countries clustered further within distinct subclades (two from Russia, three from Uzbekistan, and one Kazakhstan) according to the geographic origin of sampling. Molecular clock analysis revealed that the time to the most recent common ancestor (tMRCA) of the CRF63_02A1 epidemic was in 1996 [95% higher posterior density (95% HPD): 1992-1999], while for the two Russian subclades, tMRCA was estimated in 2003 (95% HPD: 2001-2004) and in 2007 (95% HPD: 2005-2008). Phylogeographic analysis suggested that the potential origin of the epidemic was in Uzbekistan. Early dispersal of CRF63_02A1 occurred in Kazakhstan and Uzbekistan and thereafter the epidemic spread to Russia. Notably, spillover transmissions to Russia kept occurring from both countries. Previous studies have shown that Russia and Ukraine have provided the source for the PWID-driven, HIV-1 subtype-A epidemic, spreading across the FSU countries (AFSU). In great contrast, CRF63_02A1 established an epidemic in central Asia (Uzbekistan and Kazakhstan), from where it subsequently disseminated to Russia. Our study suggests that cross-border transmissions among PWID occur bidirectionally between Russian and other FSU populations. These results are of public health importance and suggest that prevention actions have to be reinforced in this area to assist the management of high-risk practices.