五种 I 型登革热病毒的毒力差异及内在分子机制。
Virulence difference of five type I dengue viruses and the intrinsic molecular mechanism.
机构信息
Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, P. R. China.
NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai, P.R. China.
出版信息
PLoS Negl Trop Dis. 2019 Mar 4;13(3):e0007202. doi: 10.1371/journal.pntd.0007202. eCollection 2019 Mar.
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.
登革热病毒（DENV）是全球最重要的虫媒病毒。安全有效的疫苗仍在开发中，而针对 DENV 引起的疾病尚无抗病毒药物。在这项研究中，我们从中国广州 2014 年登革热爆发中获得了 5 株 DENV1 分离株（DENV1 A 至 E），并分析了它们在体外和体内的复制效率和毒力。结果表明，在这 5 株 DENV1 株中，DENV1 B 在体外的人源和蚊源细胞中具有最高的复制效率，也导致幼鼠的死亡率最高。进一步的研究表明，DENV1B 的非结构蛋白具有更高的抑制宿主干扰素信号的能力。此外，DENV1B 的 NS2B3 蛋白酶比 DENV1E 的具有更高的酶活性。最后，我们确定 NS2A 的第 64 位氨基酸和 NS2B 的第 55 位氨基酸是决定 DENV1 毒力的两个关键位点。本研究为 DENV 毒力的分子机制提供了新的证据。
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