NSs Filament Formation Is Important but Not Sufficient for RVFV Virulence In Vivo

Viruses

Pierre-Yves Lozach¹  Jeroen Kortekaas²  Zhenqiong Guan³  Wenfeng Huang³  Ke Peng³  Xiangtao Zhu³  Yulan Zhang³  Shufen Li³ 

[1] Cell Networks-Cluster of Excellence and Center for Integrative Infectious Disease Research, University Hospital Heidelberg, 69115 Heidelberg, Germany;Department of Virology, Wageningen Bioveterinary Research, 8211 Lelystad, The Netherlands;State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China;

关键词: RVFV;    reverse genetics system;    NSs;    filament;    virulence;   

DOI  :  10.3390/v11090834

来源: DOAJ

【 摘 要 】

Rift Valley fever virus (RVFV) is a mosquito-borne phlebovirus that represents as a serious health threat to both domestic animals and humans. The viral protein NSs is the key virulence factor of RVFV, and has been proposed that NSs nuclear filament formation is critical for its virulence. However, the detailed mechanisms are currently unclear. Here, we generated a T7 RNA polymerase-driven RVFV reverse genetics system based on a strain imported into China (BJ01). Several NSs mutations (T1, T3 and T4) were introduced into the system for investigating the correlation between NSs filament formation and virulence in vivo. The NSs T1 mutant showed distinct NSs filament in the nuclei of infected cells, the T3 mutant diffusively localized in the cytoplasm and the T4 mutant showed fragmented nuclear filament formation. Infection of BALB/c mice with these NSs mutant viruses revealed that the in vivo virulence was severely compromised for all three NSs mutants, including the T1 mutant. This suggests that NSs filament formation is not directly correlated with RVFV virulence in vivo. Results from this study not only shed new light on the virulence mechanism of RVFV NSs but also provided tools for future in-depth investigations of RVFV pathogenesis and anti-RVFV drug screening.

【 授权许可】

Unknown