A Single Amino Acid Substitution in the Matrix Protein (M51R) of Vesicular Stomatitis New Jersey Virus Impairs Replication in Cultured Porcine Macrophages and Results in Significant Attenuation in Pigs.
M51R
immune response
macrophages
pathogenesis
type 1 interferon
vesicular stomatitis
virulence
Journal
Frontiers in microbiology
ISSN: 1664-302X
Titre abrégé: Front Microbiol
Pays: Switzerland
ID NLM: 101548977
Informations de publication
Date de publication:
2020
2020
Historique:
received:
21
01
2020
accepted:
05
05
2020
entrez:
27
6
2020
pubmed:
27
6
2020
medline:
27
6
2020
Statut:
epublish
Résumé
In this study, we explore the virulence of vesicular stomatitis New Jersey virus (VSNJV) in pigs and its potential relationship with the virus's ability to modulate innate responses. For this purpose, we developed a mutant of the highly virulent strain NJ0612NME6, containing a single amino acid substitution in the matrix protein (M51R). The M51R mutant of NJ0612NME6 was unable to suppress the transcription of genes associated with the innate immune response both in primary fetal porcine kidney cells and porcine primary macrophage cultures. Impaired viral growth was observed only in porcine macrophage cultures, indicating that the M51 residue is required for efficient replication of VSNJV in these cells. Furthermore, when inoculated in pigs by intradermal scarification of the snout, M51R infection was characterized by decreased clinical signs including reduced fever and development of less and smaller secondary vesicular lesions. Pigs infected with M51R had decreased levels of viral shedding and absence of RNAemia compared to the parental virus. The ability of the mutant virus to infect pigs by direct contact remained intact, indicating that the M51R mutation resulted in a partially attenuated phenotype capable of causing primary lesions and transmitting to sentinel pigs. Collectively, our results show a positive correlation between the ability of VSNJV to counteract the innate immune response in swine macrophage cultures and the level of virulence in pigs, a natural host of this virus. More studies are encouraged to evaluate the interaction of VSNJV with macrophages and other components of the immune response in pigs.
Identifiants
pubmed: 32587580
doi: 10.3389/fmicb.2020.01123
pmc: PMC7299242
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1123Informations de copyright
Copyright © 2020 Velazquez-Salinas, Pauszek, Holinka, Gladue, Rekant, Bishop, Stenfeldt, Verdugo-Rodriguez, Borca, Arzt and Rodriguez.
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