Moreno, S.; Lorenzo, G.; López-Valiñas, Á.; de la Losa, N.; Alonso, C.; Charro, E.; Núñez, J.I.; Sánchez-Cordón, P.J.; Borrego, B.; Brun, A. Safety and Efficacy upon Infection in Sheep with Rift Valley Fever Virus ZH548-rA2, a Triple Mutant Rescued Virus. Viruses2024, 16, 87.
Moreno, S.; Lorenzo, G.; López-Valiñas, Á.; de la Losa, N.; Alonso, C.; Charro, E.; Núñez, J.I.; Sánchez-Cordón, P.J.; Borrego, B.; Brun, A. Safety and Efficacy upon Infection in Sheep with Rift Valley Fever Virus ZH548-rA2, a Triple Mutant Rescued Virus. Viruses 2024, 16, 87.
Moreno, S.; Lorenzo, G.; López-Valiñas, Á.; de la Losa, N.; Alonso, C.; Charro, E.; Núñez, J.I.; Sánchez-Cordón, P.J.; Borrego, B.; Brun, A. Safety and Efficacy upon Infection in Sheep with Rift Valley Fever Virus ZH548-rA2, a Triple Mutant Rescued Virus. Viruses2024, 16, 87.
Moreno, S.; Lorenzo, G.; López-Valiñas, Á.; de la Losa, N.; Alonso, C.; Charro, E.; Núñez, J.I.; Sánchez-Cordón, P.J.; Borrego, B.; Brun, A. Safety and Efficacy upon Infection in Sheep with Rift Valley Fever Virus ZH548-rA2, a Triple Mutant Rescued Virus. Viruses 2024, 16, 87.
Abstract
The introduction of three single nucleotide mutations into the genome of the virulent RVFV ZH548 strain allows the rescue of a fully attenuated virus in mice (ZH548-rA2). These mutations are located in the viral genes encoding the RdRp and the non-structural protein NSs. This paper shows the results obtained after subcutaneous inoculation of ZH548-rA2 in adult sheep and subsequent challenge with the parental virus (ZH548-rC1). Inoculation with ZH548-rA2 virus caused no detectable clinical or pathological effect in sheep, whereas inoculation of the parental rC1 virus caused lesions compatible with viral infection characterized by the presence of scattered hepatic necrosis. Viral infection was confirmed by immunohistochemistry, with hepatocytes within the necrotic foci appearing as the main cells immunolabelled against viral antigen. Furthermore, inoculation of sheep with rA2 virus prevented the liver damage expected after rC1 virus inoculation, suggesting a protective efficacy in sheep which correlated with the induction of both humoral and cell mediated immune responses.
Keywords
Rift Valley fever virus; attenuating mutations; vaccine efficacy; sheep pathology
Subject
Biology and Life Sciences, Virology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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