Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Change P82L in the Rift Valley Fever Virus NSs Protein Confers Attenuation in Mice Not Related with a Type-I IFN Antagonistic Phenotype

Version 1 : Received: 21 January 2021 / Approved: 22 January 2021 / Online: 22 January 2021 (09:47:33 CET)

A peer-reviewed article of this Preprint also exists.

Borrego, B.; Moreno, S.; de la Losa, N.; Weber, F.; Brun, A. The Change P82L in the Rift Valley Fever Virus NSs Protein Confers Attenuation in Mice. Viruses 2021, 13, 542. Borrego, B.; Moreno, S.; de la Losa, N.; Weber, F.; Brun, A. The Change P82L in the Rift Valley Fever Virus NSs Protein Confers Attenuation in Mice. Viruses 2021, 13, 542.

Abstract

Rift valley fever virus (RVFV) is a mosquito-borne bunyavirus that causes an important disease in ruminants, with great economic losses. The infection can be also transmitted to humans; therefore it is considered a major threat to both human and animal health. In a previous work, we described a novel RVFV variant selected in cell culture in the presence of the antiviral agent favipiravir that was highly attenuated in vivo. This variant displayed 24 amino acid substitutions in different viral proteins when compared to its parental viral strain, two of them located in the NSs protein that is known to be the major virulence factor of RVFV. By means of a reverse genetics system, in this work we have analyzed the effect that one of these substitutions, P82L, has in viral attenuation in vivo. Rescued viruses carrying this single amino acid change were clearly attenuated in BALB/c mice while their growth in an IFN-competent cell line as well as the production of IFN-β did not seem to be affected. However, the pattern of nuclear NSs accumulation was modified in cells infected with the mutant viruses. These results unveil a new RVFV virulence marker highlighting the multiple ways of NSs protein to modulate viral infectivity.

Keywords

Rift Valley fever virus; non-structural NSs protein; interferon antagonist; nuclear filaments; PXXP motifs

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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