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.
Highlights
Dengue virus (DENV) is currently the most popular mosquito-borne virus and widely spreads in tropical and subtropical regions[1]
The nucleotide sequences of Virulence difference of five type I dengue viruses these five DENV1 strains were determined by high throughput sequencing/assembling approach and submitted to Genebank under the accession numbers MH271402 (DENV1A) to MH271406 (DENV1E)
To test the replication efficiency of these five isolates in mammalian cells, human 293T cells were infected with DENV1 A to E respectively at the same multiplicity of infection (MOI) of 0.5
Summary
Dengue virus (DENV) is currently the most popular mosquito-borne virus and widely spreads in tropical and subtropical regions[1]. Virus nucleotide changes will eventually lead to stronger or weaker virus virulence during the long-term process of virus spread. Host response is induced upon virus infection and the interactions between host and virus influence the virulence. These two aspects corporately influence the virus pathogenicity and severity of the diseases[4,5]. It is of great significance to identify the sites within the virus genome that are associated with virulence and to investigate the interactions between virus and host
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