Phylogenetic and Mutational Analysis of the Tax Gene in the Human T-Lymphotropic Virus 1-Associated HAM/TSP in Comparison with Asymptomatic Careers.

Background: Human T-lymphotropic virus 1 (HTLV-1) is a member of the Retroviridae family that can cause two groups of diseases: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL). Despite HTLV having seven different subtypes, cosmopolitan subtype A is responsible for most HTLV-1-related disorders and is the most widely dispersed type globally, including in the Middle East, known to be an endemic area for the virus. Therefore, due to the importance of determining the subtypes of this virus, we aimed to explore the subtypes of HTLV-1 in Iran. Methods: In this cross-sectional study, we screened 140 Blood samples for HAM/TSP infection and approximately 4,500 samples for asymptomatic carriers (ACs) from Sina Hospital, Iran between 2020 and 2021. Positive samples were used for phylogenetic and mutational analysis to compare ACs and HAM/TSP cases via the Tax segment of HTLV. To identify the genotype of positive samples, the Maximum Likelihood method was used to construct the phylogenetic tree based on the positive samples. Results: All Iranian isolates were clustered as HTLV-1a subgroups. Moreover, all of our samples have undergone positive selection pressure. Furthermore, we detected unique mutations in Iranian HAM/TSP and ACs sequences. Conclusion: All of the Iranian Tax proteins are under positive selection pressure with respect to Japanese isolates. Interestingly, we detect specific mutation patterns in the sequences. Positions 51, 82, 109, 172, 232, and 339 in the aa sequence have undergone mutations specific to Iranian HTLV-1; and in positions 22 and 146 aa we detected mutations unique to ACs and HAM/TSP, respectively.