Risks Posed by Reston, the Forgotten Ebolavirus.
Risks Posed by Reston, the Forgotten Ebolavirus.
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DOI：
10.1128/msphere.00322-16
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发表时间：
2016-11
期刊：
影响因子：
4.8
通讯作者：
Rossman JS
中科院分区：
文献类型：
--
作者：
Cantoni D;Hamlet A;Michaelis M;Wass MN;Rossman JS
在埃博拉病毒家族的五个成员中，有四个会导致危及生命的疾病，而第五个，莱斯顿病毒（RESTV），在人类中是非致病性的。在埃博拉病毒家族的五个成员中，有四个会导致危及生命的疾病，而第五个，莱斯顿病毒（RESTV），在人类中是非致病性的。造成这种差异的原因尚不清楚。在这篇综述中，我们分析了目前可用的信息，以提供一个国家的最先进的总结的因素，确定人类的埃博拉病毒的致病性。RESTV在食蟹猴中引起散发性感染，并在菲律宾和中国的家猪中发现。系统发育分析显示，RESTV与苏丹病毒关系最密切，后者导致人类高死亡率。RESTV和其他埃博拉病毒之间的氨基酸序列差异存在于所有9种埃博拉病毒蛋白中，尽管没有一个残基足以赋予致病性。糖蛋白的变化有助于埃博拉病毒致病性的差异，但不足以赋予其自身的致病性。类似地，VP24和VP35的差异影响病毒免疫逃避，并与人类致病性的变化相关。最近的计算机分析系统地确定了RESTV和人类致病性埃博拉病毒之间序列变异的功能后果。VP24中的多个位置在RESTV和其他埃博拉病毒之间是不同保守的，并且可能改变人类致病性。总之，决定埃博拉病毒在人类中致病性的因素仍然没有得到充分的了解。对这些致病性决定因素的进一步了解对于疾病预防和早期发现紧急和潜在的人类致病性RESTV至关重要。
Out of the five members of the Ebolavirus family, four cause life-threatening disease, whereas the fifth, Reston virus (RESTV), is nonpathogenic in humans. Out of the five members of the Ebolavirus family, four cause life-threatening disease, whereas the fifth, Reston virus (RESTV), is nonpathogenic in humans. The reasons for this discrepancy remain unclear. In this review, we analyze the currently available information to provide a state-of-the-art summary of the factors that determine the human pathogenicity of Ebolaviruses. RESTV causes sporadic infections in cynomolgus monkeys and is found in domestic pigs throughout the Philippines and China. Phylogenetic analyses revealed that RESTV is most closely related to the Sudan virus, which causes a high mortality rate in humans. Amino acid sequence differences between RESTV and the other Ebolaviruses are found in all nine Ebolavirus proteins, though no one residue appears sufficient to confer pathogenicity. Changes in the glycoprotein contribute to differences in Ebolavirus pathogenicity but are not sufficient to confer pathogenicity on their own. Similarly, differences in VP24 and VP35 affect viral immune evasion and are associated with changes in human pathogenicity. A recent in silico analysis systematically determined the functional consequences of sequence variations between RESTV and human-pathogenic Ebolaviruses. Multiple positions in VP24 were differently conserved between RESTV and the other Ebolaviruses and may alter human pathogenicity. In conclusion, the factors that determine the pathogenicity of Ebolaviruses in humans remain insufficiently understood. An improved understanding of these pathogenicity-determining factors is of crucial importance for disease prevention and for the early detection of emergent and potentially human-pathogenic RESTVs.