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

Shufen Li,Yulan Zhang,Pierre-Yves Lozach,Jeroen Kortekaas,Xiangtao Zhu,Zhenqiong Guan,Ke Peng,Wenfeng Huang

doi:10.3390/v11090834

Abstract

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.

Highlights

Rift Valley fever (RVF) is a mosquito-borne anthropozoonosis caused by the RVF virus (RVFV), which belongs to the family Phenuiviridae in the order of Bunyavirales [1]
RNA polymerase-dependent system that relies on the T7 promoter for the synthesis of viral transcripts, the anti-genomic full-length segments L, M and S from RVFV were cloned into the vector pVSV-T7, which contains a T7 promoter and terminator
Investigating the virulence mechanism of RVFV is critical for understanding its pathogenesis, and

Summary

Introduction

Rift Valley fever (RVF) is a mosquito-borne anthropozoonosis caused by the RVF virus (RVFV), which belongs to the family Phenuiviridae in the order of Bunyavirales [1]. RVFV is a negative-sense single-stranded RNA virus with a segmented genome, comprising large (L), medium (M) and small (S). Sheep are most susceptible to infection, manifesting with abortion of pregnant animals and acute mortality among newborns. Humans can become infected via contact with tissues and fluids released during the slaughtering of infected animals or via bites of infected mosquitoes [3]. Infected humans usually remain asymptomatic or develop a self-limiting febrile illness. In some cases, patients develop severe complications manifesting with acute hepatitis, encephalitis or hemorrhagic fever

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Conclusion