Virulence difference of five type I dengue viruses and the intrinsic molecular mechanism.

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 Gu...

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Bibliographic Details
Published in:PLOS Neglected Tropical Diseases
Main Authors: Chunling Zou, Chenxiao Huang, Jinyu Zhang, Qihan Wu, Xiaohua Ni, Jiufeng Sun, Jianfeng Dai
Format: Article in Journal/Newspaper
Language:English
Published: Public Library of Science (PLoS) 2019
Subjects:
Online Access:https://doi.org/10.1371/journal.pntd.0007202
https://doaj.org/article/36495a146f424b9183138b7145511f73
Description
Summary: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.