Abstract

HIV-1 Circulating Recombinant Form 35_AD (CRF35_AD) has an important position in the epidemiological profile of Afghanistan and Iran. Despite the presence of this clade in Afghanistan and Iran for over a decade, our understanding of its origin and dissemination patterns is limited. In this study, we performed a Bayesian phylogeographic analysis to reconstruct the spatio-temporal dispersion pattern of this clade using eligible CRF35_AD gag and pol sequences available in the Los Alamos HIV database (432 sequences available from Iran, 16 sequences available from Afghanistan, and a single CRF35_AD-like pol sequence available from USA). Bayesian Markov Chain Monte Carlo algorithm was implemented in BEAST v1.8.1. Between-country dispersion rates were tested with Bayesian stochastic search variable selection method and were considered significant where Bayes factor values were greater than three. The findings suggested that CRF35_AD sequences were genetically similar to parental sequences from Kenya and Uganda, and to a set of subtype A1 sequences available from Afghan refugees living in Pakistan. Our results also showed that across all phylogenies, Afghan and Iranian CRF35_AD sequences formed a monophyletic cluster (posterior clade credibility> 0.7). The divergence date of this cluster was estimated to be between 1990 and 1992. Within this cluster, a bidirectional dispersion of the virus was observed across Afghanistan and Iran. We could not clearly identify if Afghanistan or Iran first established or received this epidemic, as the root location of this cluster could not be robustly estimated. Three CRF35_AD sequences from Afghan refugees living in Pakistan nested among Afghan and Iranian CRF35_AD branches. However, the CRF35_AD-like sequence available from USA diverged independently from Kenyan subtype A1 sequences, suggesting it not to be a true CRF35_AD lineage. Potential factors contributing to viral exchange between Afghanistan and Iran could be injection drug networks and mass migration of Afghan refugees and labours to Iran, which calls for extensive preventive efforts.

Highlights

  • Human immunodeficiency virus type 1 (HIV-1), is a highly mutating RNA virus [1]

  • The results indicated that among all parental sequences available worldwide, CRF35_AD sequences were genetically similar to parental sequences from Kenya, Uganda, and a cluster containing Afghan refugees living in Pakistan and Native Pakistanis (S1 Fig)

  • Our results suggested the epidemic in Afghanistan and Iran to have started at around 1990–1992 and showed an ongoing bidirectional dispersion of the virus between both countries

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Summary

Introduction

Human immunodeficiency virus type 1 (HIV-1), is a highly mutating RNA virus [1]. HIV-1 group M, the pandemic branch of HIV, is reported to have originated from western-central Africa in around 1900–1930 and started to spread around the world from the 1950s [2, 3]. HIV-1 Circulating Recombinant Form 35_AD (CRF35_AD), a group M recombinant, is the result of subtype A1 and subtype D recombination. Molecular epidemiological studies suggest the predominance of HIV-1 CRF35_AD in both Afghanistan and Iran [5,6,7,8,9,10,11,12]. Data on the Los Alamos HIV database show that of the total number of HIV-1 sequences available from Afghanistan (n = 26) and Iran (n = 974), respectively 756 (78%) and 16 (67%) sequences are of CRF35_AD classification [4]. Other than Afghanistan and Iran, CRF35_AD was only reported from three Afghan refugees living in Pakistan (in 2009) [13]; the clade has not yet been reported among Native Pakistanis. A CRF35_AD-like pol sequence, is reported from a 36-year-old woman living in USA (in 2010), with unknown source of infection [14]

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