World Reference Center for Emerging Viruses and Arboviruses, Institute for Human Infections and Immunity, and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
Department of Biochemistry and Molecular Biology and Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, 77555, USA.
Nat Commun. 2021 Jan 26;12(1):595. doi: 10.1038/s41467-020-20747-3.
Zika virus (ZIKV) emerged from obscurity in 2013 to spread from Asia to the South Pacific and the Americas, where millions of people were infected, accompanied by severe disease including microcephaly following congenital infections. Phylogenetic studies have shown that ZIKV evolved in Africa and later spread to Asia, and that the Asian lineage is responsible for the recent epidemics in the South Pacific and Americas. However, the reasons for the sudden emergence of ZIKV remain enigmatic. Here we report evolutionary analyses that revealed four mutations, which occurred just before ZIKV introduction to the Americas, represent direct reversions of previous mutations that accompanied earlier spread from Africa to Asia and early circulation there. Our experimental infections of Aedes aegypti mosquitoes, human cells, and mice using ZIKV strains with and without these mutations demonstrate that the original mutations reduced fitness for urban, human-amplifed transmission, while the reversions restored fitness, increasing epidemic risk. These findings include characterization of three transmission-adaptive ZIKV mutations, and demonstration that these and one identified previously restored fitness for epidemic transmission soon before introduction into the Americas. The initial mutations may have followed founder effects and/or drift when the virus was introduced decades ago into Asia.
寨卡病毒（ZIKV）于 2013 年从默默无闻中出现，从亚洲传播到南太平洋和美洲，数百万人感染了这种病毒，同时还伴有包括先天性感染后小头畸形在内的严重疾病。系统发育研究表明，ZIKV 在非洲进化，后来传播到亚洲，而亚洲谱系是导致最近南太平洋和美洲流行的原因。然而，寨卡病毒突然出现的原因仍然是个谜。在这里，我们报告了进化分析，这些分析显示，在寨卡病毒传入美洲之前发生的四个突变，是之前伴随其从非洲传播到亚洲和早期在那里循环的突变的直接回复。我们使用具有和不具有这些突变的寨卡病毒株对埃及伊蚊、人类细胞和小鼠进行的实验感染表明，原始突变降低了在城市中、人类传播的适应性，而回复突变则恢复了适应性，增加了流行风险。这些发现包括对三个传播适应性寨卡病毒突变的特征描述，并证明这些突变以及之前确定的一个突变在病毒几十年前引入亚洲之前不久就恢复了流行传播的适应性。最初的突变可能是在几十年前病毒传入亚洲时伴随着创始效应和/或漂变而产生的。
