Geographic characteristics of HTLV-1 molecular subgroups and genetic substitutions in East Asia: Insights from complete genome sequencing of HTLV-1 strains isolated in Taiwan and Japan.

Background: Although Japan is a major endemic area for human T-lymphotropic virus type 1 (HTLV-1) and the virus has been well-studied in this region, there is limited research on HTLV-1 in surrounding regions. In this study, we determined the complete genome sequences of HTLV-1 strains isolated from Taiwan and Japan and investigated the geographic characteristics of molecular subgroups and substitution mutations to understand the spread of HTLV-1 and its correlation with human migration. Methodology/Principal findings: The complete genome sequences of 26 HTLV-1 isolates from Taiwan were determined using next-generation sequencing and were compared with those of 211 isolates from Japan in terms of subgroup and genetic mutations. In total, 15/26 (58%) isolates from Taiwan belonged to the transcontinental subgroup and 11/26 (42%) isolates belonged to the Japanese subgroup. The transcontinental subgroup was significantly more prevalent among Taiwanese isolates than Japanese isolates (58% vs 18%, P < 0.0001). The mutation rate for the complete HTLV-1 sequence was as low as 0.2%. On examining individual base substitutions, the G-to-A mutation was predominant. Bayesian phylogenetic tree analysis estimated the time to the most recent common ancestor for the transcontinental and Japanese subgroups to be 28447 years. The transcontinental subgroups from Taiwan and Japan appeared to form clusters according to their respective regions. Conclusions/Significance: The transcontinental subgroup of HTLV-1 is predominant in Taiwan, while the Japanese subgroup is common in Japan. The difference in subgroup distribution may be attributed to the initial spread of the transcontinental subgroup in East Asia, followed by the influx of the Japanese subgroup. Author summary: Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects 5–10 million people worldwide. HTLV-1 infection can cause serious diseases including hematologic malignancy, adult T-cell leukemia/lymphoma (ATL), and progressive neurologic disease known as HTLV-1-associated myelopathy/tropical spastic paraplegia (HAM/TSP). An increase in the mortality rate among HTLV-1-infected individuals has become an issue of concern in recent years. Differences in HTLV-1 infection rates and subgroup distribution are considered to be caused by the historical global movement of HTLV-1-infected individuals. Furthermore, recent global population movements have resulted in the redistribution of HTLV-1-infected individuals, which may lead to outbreaks of ATL and HAM/TSP in non-endemic areas. In this study, we investigated the molecular characteristics of HTLV-1 in East Asia and found that the transcontinental subgroup was more prevalent in Taiwan, whereas the Japanese subgroup was common in Japan. The difference in subgroup distribution may be attributed to the initial spread of the transcontinental subgroup in East Asia, followed by the influx of the Japanese subgroup. [ABSTRACT FROM AUTHOR]