Data_Sheet_1_Genetic Diversity and Phylogeography of Thottapalayam thottimvirus (Hantaviridae) in Asian House Shrew (Suncus murinus) in Eurasia.zip

Murid and cricetid rodents were previously believed to be the principal reservoir hosts of hantaviruses. Recently, however, multiple newfound hantaviruses have been discovered in shrews, moles, and bats, suggesting a complex evolutionary history. Little is known about the genetic diversity and geographic distribution of the prototype shrew-borne hantavirus, Thottapalayam thottimvirus (TPMV), carried by the Asian house shrew (Suncus murinus), which is widespread in Asia, Africa, and the Middle East. Comparison of TPMV genomic sequences from two Asian house shrews captured in Myanmar and Pakistan with TPMV strains in GenBank revealed that the Myanmar TPMV strain (H2763) was closely related to the prototype TPMV strain (VRC66412) from India. In the L-segment tree, on the other hand, the Pakistan TPMV strain (PK3629) appeared to be the most divergent, followed by TPMV strains from Nepal, then the Indian-Myanmar strains, and finally TPMV strains from China. The Myanmar strain of TPMV showed sequence similarity of 79.3–96.1% at the nucleotide level, but the deduced amino acid sequences showed a high degree of conservation of more than 94% with TPMV strains from Nepal, India, Pakistan, and China. Cophylogenetic analysis of host cytochrome b and TPMV strains suggested that the Pakistan TPMV strain was mismatched. Phylogenetic trees, based on host cytochrome b and cytochrome c oxidase subunit I genes of mitochondrial DNA, and on host recombination activating gene 1 of nuclear DNA, suggested that the Asian house shrew and Asian highland shrew (Suncus montanus) comprised a species complex. Overall, the geographic-specific clustering of TPMV strains in Asian countries suggested local host-specific adaptation. Additional in-depth studies are warranted to ascertain if TPMV originated in Asian house shrews on the Indian subcontinent.

此前学界认为鼠科（Murid）与仓鼠科（Cricetid）啮齿动物是汉坦病毒（Hantavirus）的主要储存宿主。然而近期多项研究在鼩鼱、鼹鼠及蝙蝠体内发现了多种新型汉坦病毒，提示汉坦病毒拥有复杂的进化历史。目前学界对首例鼩鼱携带的汉坦病毒——托塔帕拉姆病毒（Thottapalayam thottimvirus，TPMV）的遗传多样性与地理分布特征仍知之甚少；该病毒由广泛分布于亚洲、非洲及中东地区的臭鼩（Suncus murinus）携带。
对捕获自缅甸与巴基斯坦的2只臭鼩体内的TPMV基因组序列，与GenBank中收录的TPMV毒株进行比对后发现：缅甸TPMV毒株（H2763）与印度来源的原型TPMV毒株（VRC66412）亲缘关系紧密。而在L片段系统发育树中，巴基斯坦TPMV毒株（PK3629）的分化程度最高，其次为尼泊尔TPMV毒株，随后是印缅毒株，最后为中国TPMV毒株。缅甸TPMV毒株的核苷酸序列相似度为79.3%~96.1%，但其推导的氨基酸序列与尼泊尔、印度、巴基斯坦及中国的TPMV毒株保守度均超过94%。
对宿主细胞色素b（cytochrome b）基因与TPMV毒株的共系统发育分析显示，巴基斯坦TPMV毒株存在宿主-病毒系统发育匹配失调现象。基于宿主线粒体DNA的细胞色素b、细胞色素C氧化酶亚基I基因，以及宿主核DNA的重组激活基因1（recombination activating gene 1，RAG1）构建的系统发育树显示，臭鼩与亚洲高地鼩（Suncus montanus）构成一个物种复合群。
总体而言，亚洲各国的TPMV毒株呈现地理特异性聚类的特征，提示其存在宿主特异性的本地适应性演化。仍需开展进一步的深入研究，以明确TPMV是否起源于印度次大陆的臭鼩种群。