Viral determinants that drive Enterovirus-A71 fitness and virulence.
Viral determinants that drive Enterovirus-A71 fitness and virulence.
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DOI：
10.1080/22221751.2021.1906754
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发表时间：
2021-12
影响因子：
13.2
通讯作者：
Alonso S
中科院分区：
文献类型：
--
作者：
Ang PY;Chong CWH;Alonso S
手足口病（HFMD）通常是一种自限性的轻度儿童疾病，主要由小核糖核酸病毒科的科萨基病毒A16（CVA 16）和肠道病毒A71（EV-A71）引起。然而，由于EV-A71感染在西太平洋地区反复发生的手足口病爆发和流行，以及EV-A71毒株引起严重神经系统并发症的倾向，使得这种嗜神经病毒成为受影响国家的严重公共卫生问题。导致病毒准种的高突变率与共循环EV-A71毒株之间频繁的型内和型间重组事件相结合，导致EV-A71基因组的巨大多样性和快速进化，使得不可能准确预测下一个流行毒株。比较基因组序列分析和诱变方法已经导致鉴定了许多参与EV-A71适应性和毒力的病毒决定簇。这些病毒决定簇包括位于病毒结构蛋白中的氨基酸残基，影响与宿主细胞表面的附着、受体结合和脱壳事件。非结构蛋白中的关键残基也已被鉴定，包括2C、3A、3C蛋白酶和RNA依赖性RNA聚合酶。最后，还发现改变5'非翻译区中的关键二级结构的突变影响EV-A71适应性和毒力。虽然我们目前对EV-A71发病机制的理解仍然不完整，但这些研究可能有助于合理设计有效的治疗方法和广泛保护的候选疫苗。
Hand, Foot and Mouth Disease (HFMD) is usually a self-limiting, mild childhood disease that is caused mainly by Coxsackie virus A16 (CVA16) and Enterovirus A71 (EV-A71), both members of the Picornaviridae family. However, recurring HFMD outbreaks and epidemics due to EV-A71 infection in the Western Pacific region, and the propensity of EV-A71 strains to cause severe neurological complications have made this neurotropic virus a serious public health concern in afflicted countries. High mutation rate leading to viral quasispecies combined with frequent intra- and inter-typic recombination events amongst co-circulating EV-A71 strains have contributed to the great diversity and fast evolution of EV-A71 genomes, making impossible any accurate prediction of the next epidemic strain. Comparative genome sequence analyses and mutagenesis approaches have led to the identification of a number of viral determinants involved in EV-A71 fitness and virulence. These viral determinants include amino acid residues located in the structural proteins of the virus, affecting attachment to the host cell surface, receptor binding, and uncoating events. Critical residues in non-structural proteins have also been identified, including 2C, 3A, 3C proteases and the RNA-dependent RNA polymerase. Finally, mutations altering key secondary structures in the 5’ untranslated region were also found to influence EV-A71 fitness and virulence. While our current understanding of EV-A71 pathogenesis remains fragmented, these studies may help in the rational design of effective treatments and broadly protective vaccine candidates.
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影响因子：
4.8
作者：
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通讯作者：
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影响因子：
6.7
作者：
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影响因子：
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作者：
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影响因子：
3.7
作者：
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通讯作者：
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影响因子：
5.2
作者：
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通讯作者：
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