The Change P82L in the Rift Valley Fever Virus NSs Protein Confers Attenuation in Mice.

Belén Borrego,Alejandro Brun,Nuria De La Losa,Friedemann Weber,Sandra Moreno

doi:10.3390/v13040542

Belén Borrego, Alejandro Brun + Show 3 more

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https://doi.org/10.3390/v13040542

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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 interferon (IFN)-competent cell line as well as the production of interferon beta (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 highlight the key role of the NSs protein in the modulation of viral infectivity.

Highlights

In a previous work aimed to characterize a novel Rift valley fever virus (RVFV) variant that was selected in cell culture in the presence of the antiviral compound favipiravir, we found that this virus, named as 40F-p8, was highly attenuated in vivo [14]
We planned to rescue recombinant ZH548 viruses carrying the amino acid substitution P82L in the NSs protein by means of our reverse genetic system [17]. This amino acid change was deduced from the nucleotide sequence of the virus 40F-p8 that displayed the change C279T in the corresponding codon
We describe the rescue of recombinant ZH548 RVF viruses carrying a P82L mutated NSs protein and analyze the effect of this change in RVFV

Summary

Introduction

Academic Editors: Esther Schnettler and Benjamin Brennan. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rift valley fever virus (RVFV) is a mosquito-borne phlebovirus of the Phenuiviridae family Bunyavirales) that causes an important disease in ruminants, mostly characterized by a high-rate of abortions, fetal malformation and death of newborn lambs, with great economic losses. The infection can be transmitted to humans through mosquito bites or when exposed to infected material, producing a usually self-limiting disease with more severe development in a low percentage of cases (reviewed in [1]).

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