Possible Roles of New Mutations Shared by Asian and American Zika Viruses.
Possible Roles of New Mutations Shared by Asian and American Zika Viruses.
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DOI：
10.1093/molbev/msw270
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发表时间：
2017-03-01
影响因子：
10.7
通讯作者：
Starmer WT
中科院分区：
文献类型：
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作者：
Yokoyama S;Starmer WT
寨卡病毒（ZIKV）起源于非洲，已传播至亚洲、太平洋岛屿，现在又传播到美洲及其他地区。自1947年首次被分离出来后，在过去69年的不同时间里对寨卡病毒株进行了采样，但在研究其基因组的突变积累模式时，这段历史并未得到体现。通过梳理该病毒的历史，我们发现寨卡病毒的祖先大约在1930年至1945年期间出现，当时其突变率可能低于每年每个核苷酸位点0.2×10⁻³，并且在其大多数后代中突变率显著增加。从马来西亚一只蚊子身上采集到的亚洲祖先株在其整个进化过程中保持着每年每个位点4×10⁻³的高突变率，在1963年之前，它在RNA茎环的3′ - 非翻译区积累了13个突变，其中7个突变产生了更稳定的茎环结构，可能会抑制细胞的抗病毒活性，包括免疫和RNA干扰（RNAi）途径。这7个突变在所有亚洲和美洲的病毒株中都得以保留，可能是我们如今面临的严重医学问题的原因，并为研究它们在大脑发育过程中的分子相互作用中的作用提供了可验证的假设。
Originating in Africa, the Zika virus (ZIKV) has spread to Asia, Pacific Islands and now to the Americas and beyond. Since the first isolation in 1947, ZIKV strains have been sampled at various times in the last 69 years, but this history has not been reflected in studying the patterns of mutation accumulation in their genomes. Implementing the viral history, we show that the ZIKV ancestor appeared sometime in 1930–1945 and, at that point, its mutation rate was probably less than 0.2 × 10−3/nucleotide site/year and subsequently increased significantly in most of its descendants. Sustaining a high mutation rate of 4 × 10−3/site/year throughout its evolution, the Ancestral Asian strain, which was sampled from a mosquito in Malaysia, accumulated 13 mutations in the 3′-untranslated region of RNA stem-loops prior to 1963, seven of which generate more stable stem-loop structures and are likely to inhibit cellular antiviral activities, including immune and RNA interference (RNAi) pathways. The seven mutations have been maintained in all Asian and American strains and may be responsible for serious medical problems we are facing today and offer testable hypotheses to examine their roles in molecular interactions during brain development.