Phylogenetic and phylodynamic study of Human T-cell lymphotropic virus Type 1 (HTLV-1) in Iran.

Human T-lymphotropic virus type-1 (HTLV-1) is a retrovirus that causes the neurological disorder HTLV-1 associated myelopathy/ tropical spastic paraparesis (HAM/TSP) and/or adult T-cell leukemia/lymphoma (ATLL). Iran is one of the endemic regions of the HTLV-1 in the Middle East. To infer the origin of the virus in Iran and to follow the movements of human population and routes of virus spread to this country, phylogenetic and phylodynamic analyses were performed. To this purpose, the long terminal repeat (LTR) region of HTLV-1 was used. New LTR sequences were obtained from 100 blood samples which infected with HTLV-1. Moreover, all Iranian LTR sequences which have been reported so far, were obtained from GenBank database. Sequences were aligned and maximum-likelihood and Bayesian tree topologies were explored. After identification of Iranian specific cluster, molecular-clock and coalescent models were used to estimate time to the most recent common ancestor (tMRCA). Bayesian Skyline Plots (BSP), representing population dynamics HTLV-1 strains back to the MRCA, were estimated using BEAST software. Phylogenetic analysis demonstrated that the Iranian, Kuwaiti, German, Israelite and southern Indian isolates are located within the widespread "transcontinental" subgroup A clade of HTLV-1 Cosmopolitan subtype a. Molecular clock analysis of the Iranian cluster dated back their respective tMRCA to be 1290 AC with a 95% HPD confidence intervals (918, 1517). BSPs indicated a rapid exponential growth rate in the effective number of infections prior the 15th century. Our results support the hypothesis of a multiple introductions of HTLV-1 into Iran with the majority of introductions occurring in prior the 15th century, at the same time the Mongol invasion of Iran. Our results further suggest that HTLV-1 introduction into Iran was facilitated by the commercial/migratory linkage as known as the ancient Silk Road which linked China to Antioch (now in Turkey).