Virulence difference of five type I dengue viruses and the intrinsic molecular mechanism
Virulence difference of five type I dengue viruses and the intrinsic molecular mechanism
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五种I型登革热病毒毒力差异及其内在分子机制
DOI：
10.1371/journal.pntd.0007202
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发表时间：
2019
影响因子：
3.8
通讯作者：
Dai Jianfeng
中科院分区：
文献类型：
--
作者：
Zou Chunling;Huang Chenxiao;Zhang Jinyu;Wu Qihan;Ni Xiaohua;Sun Jiufeng;Dai Jianfeng
登革病毒（DENV）是全球最重要的媒介传播病毒。安全有效的疫苗仍在开发中，没有针对DENV引起的疾病的抗病毒药物。本研究从2014年中国广州登革热暴发疫情中分离到5株DENV 1（DENV 1 A ~ E），并对其进行了体外和体内复制效率和毒力分析。结果表明，5株DENV 1中，DENV 1 B在人和蚊细胞中的体外复制效率最高，对乳鼠的致死率也最高。进一步的研究表明，来自DENV 1B的非结构蛋白具有更高的抑制宿主干扰素信号传导的能力。另外，DENV 1B的NS 2B 3蛋白酶与DENV 1 E的NS 2B 3蛋白酶相比具有更高的酶活性。最终确定NS 2A的第64位氨基酸和NS 2B的第55位氨基酸是DENV 1的两个毒力决定位点。本研究为DENV毒力的分子机制提供了新的证据。
Dengue virus (DENV) is the most important vector-borne virus globally. The safe and effective vaccines are still under development and there are no antiviral drugs for DENV induced diseases. In this study, we obtained five DENV1 isolates (DENV1 A to E) from the outbreak of dengue fever in 2014 of Guangzhou, China, and analyzed their replication efficiency and virulence in vitro and in vivo. The results suggested that among the five DENV1 strains, DENV1 B has the highest replication efficiency in both human and mosquito cells in vitro, also causes the highest mortality to suckling mice. Further study suggested that nonstructural proteins from DENV1B have higher capacity to suppress host interferon signaling. In addition, the NS2B3 protease from DENV1B has higher enzymatic activity compared with that from DENV1 E. Finally, we identified that the 64th amino acid of NS2A and the 55th amino acid of NS2B were two virulence determining sites for DENV1. This study provided new evidences of the molecular mechanisms of DENV virulence.