Ueda Mahoko Takahashi, Kurosaki Yohei, Izumi Taisuke, Nakano Yusuke, Oloniniyi Olamide K, Yasuda Jiro, Koyanagi Yoshio, Sato Kei, Nakagawa So
Micro/Nano Technology Center, Tokai University, 411 Kitakaname, Hiratsuka, Kanagawa, 259-1193, Japan.
Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
Genes Cells. 2017 Feb;22(2):148-159. doi: 10.1111/gtc.12463. Epub 2017 Jan 13.
Ebola virus (EBOV) is extremely virulent, and its glycoprotein is necessary for viral entry. EBOV may adapt to its new host humans during outbreaks by acquiring mutations especially in glycoprotein, which allows EBOV to spread more efficiently. To identify these evolutionary selected mutations and examine their effects on viral infectivity, we used experimental-phylogenetic-structural interdisciplinary approaches. In evolutionary analysis of all available Zaire ebolavirus glycoprotein sequences, we detected two codon sites under positive selection, which are located near/within the region critical for the host-viral membrane fusion, namely alanine-to-valine and threonine-to-isoleucine mutations at 82 (A82V) and 544 (T544I), respectively. The fine-scale transmission dynamics of EBOV Makona variants that caused the 2014-2015 outbreak showed that A82V mutant was fixed in the population, whereas T544I was not. Furthermore, pseudotype assays for the Makona glycoprotein showed that the A82V mutation caused a small increase in viral infectivity compared with the T544I mutation. These findings suggest that mutation fixation in EBOV glycoprotein may be associated with their increased infectivity levels; the mutant with a moderate increase in infectivity will fix. Our findings showed that a driving force for Ebola virus evolution via glycoprotein may be a balance between costs and benefits of its virulence.
埃博拉病毒（EBOV）极具毒性，其糖蛋白是病毒进入宿主细胞所必需的。在疫情爆发期间，EBOV可能通过获取突变，特别是糖蛋白中的突变来适应其新宿主人类，从而使EBOV能够更有效地传播。为了识别这些经过进化选择的突变并研究它们对病毒感染性的影响，我们采用了实验-系统发育-结构跨学科方法。在对所有可用的扎伊尔埃博拉病毒糖蛋白序列进行进化分析时，我们检测到两个处于正选择状态的密码子位点，它们分别位于宿主-病毒膜融合关键区域附近/内部，即82位的丙氨酸到缬氨酸突变（A82V）和544位的苏氨酸到异亮氨酸突变（T544I）。对导致2014 - 2015年疫情爆发的EBOV Makona变体的精细传播动态分析表明，A82V突变体在群体中固定下来，而T544I突变体则没有。此外，对Makona糖蛋白的假型试验表明，与T544I突变相比，A82V突变导致病毒感染性略有增加。这些发现表明，EBOV糖蛋白中的突变固定可能与其感染性水平的提高有关；感染性适度增加的突变体将被固定下来。我们的研究结果表明，埃博拉病毒通过糖蛋白进化的驱动力可能是其毒力成本与收益之间的平衡。
