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

Chunling Zou; Chenxiao Huang; Jinyu Zhang; Qihan Wu; Xiaohua Ni; Jiufeng Sun; Jianfeng Dai

doi:10.1371/journal.pntd.0007202

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

PLoS Negl Trop Dis. 2019 Mar 4;13(3):e0007202. doi: 10.1371/journal.pntd.0007202. eCollection 2019 Mar.

Authors

Chunling Zou¹, Chenxiao Huang¹, Jinyu Zhang¹, Qihan Wu², Xiaohua Ni², Jiufeng Sun³, Jianfeng Dai¹

Affiliations

¹ Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, P. R. China.
² NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai, P.R. China.
³ Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, P.R. China.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
China
Culicidae
Dengue / blood
Dengue / immunology
Dengue / virology*
Dengue Virus / genetics*
Dengue Virus / immunology
Dengue Virus / isolation & purification
Dengue Virus / pathogenicity*
HEK293 Cells
Human Umbilical Vein Endothelial Cells
Humans
Interferons / metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Peptide Hydrolases / genetics
Peptide Hydrolases / metabolism
Viral Nonstructural Proteins / genetics
Viral Nonstructural Proteins / metabolism
Virulence
Virus Replication / genetics

Substances

Viral Nonstructural Proteins
Interferons
Peptide Hydrolases

Grants and funding

This work was supported by a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT), National Natural Science Foundation of China (31770933, 81471571 (J.D.) and 81872103 (N.X.)), Natural Science Foundation of Colleges in Jiangsu Province (17KJA310005)(J.D.), Open Project Fund from Key Laboratory of Reproduction Regulation of NHC (No. KF2018-01) (J.D.) and Science and Technology Climbing Fund of SIPPR (No.PD2017-2)(N.X.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.