Comparative genomic analysis of pre-epidemic and epidemic Zika virus strains for virological factors potentially associated with the rapidly expanding epidemic.
Comparative genomic analysis of pre-epidemic and epidemic Zika virus strains for virological factors potentially associated with the rapidly expanding epidemic.
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DOI：
10.1038/emi.2016.48
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发表时间：
2016-03-16
影响因子：
13.2
通讯作者：
Yuen KY
中科院分区：
文献类型：
--
作者：
Zhu Z;Chan JF;Tee KM;Choi GK;Lau SK;Woo PC;Tse H;Yuen KY
在2007年之前，非洲和亚洲报告的人寨卡病毒（ZIKV）感染的零星病例不到20例，但自2007年以来，太平洋岛屿上多达73%的人口开始大规模爆发，并于2014年蔓延到美洲。此外，ZIKV感染的临床表现已经明显改变，如神经系统并发症的报告增加所证明的，例如成人中的格林-巴利综合征和新生儿中的先天性异常。我们将流行前和流行ZIKV毒株的基因组序列与GenBank中可获得的完整基因组或完整多蛋白序列进行了全面比较。除已报道的流行株与亚洲株的系统发生树聚类外，我们发现除非结构2B（NS 2B）编码区外，其他编码区的系统发生树拓扑结构均相同。这一发现得到了bootscan分析和多重序列比对的证实，表明在NS 2B处存在与Spondweni病毒基因重组的片段。此外，代表性流行株在1947年流行前原型株的NS 5终止密码子远端的3′-非翻译区的第一个茎环结构上具有一个9个碱基的大凸起，而不是外部环。流行株与流行前相比，有15个氨基酸发生了替换。由于其他黄病毒中的突变可能与毒力、复制效率、抗原表位和宿主嗜性的变化相关，因此进一步的研究对于确定这些基因组变化的生物学意义至关重要。
Less than 20 sporadic cases of human Zika virus (ZIKV) infection were reported in Africa and Asia before 2007, but large outbreaks involving up to 73% of the populations on the Pacific islands have started since 2007, and spread to the Americas in 2014. Moreover, the clinical manifestation of ZIKV infection has apparently changed, as evident by increasing reports of neurological complications, such as Guillain–Barré syndrome in adults and congenital anomalies in neonates. We comprehensively compared the genome sequences of pre-epidemic and epidemic ZIKV strains with complete genome or complete polyprotein sequences available in GenBank. Besides the reported phylogenetic clustering of the epidemic strains with the Asian lineage, we found that the topology of phylogenetic tree of all coding regions is the same except that of the non-structural 2B (NS2B) coding region. This finding was confirmed by bootscan analysis and multiple sequence alignment, which suggested the presence of a fragment of genetic recombination at NS2B with that of Spondweni virus. Moreover, the representative epidemic strain possesses one large bulge of nine bases instead of an external loop on the first stem-loop structure at the 3′-untranslated region just distal to the stop codon of the NS5 in the 1947 pre-epidemic prototype strain. Fifteen amino acid substitutions are found in the epidemic strains when compared with the pre-epidemic strains. As mutations in other flaviviruses can be associated with changes in virulence, replication efficiency, antigenic epitopes and host tropism, further studies would be important to ascertain the biological significance of these genomic changes.