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
Por:
Velazquez-Salinas, Lauro, Pauszek, Steven J., Holinka, Lauren G., Gladue, Douglas P., Rekant, Steven I., Bishop, Elizabeth A., Stenfeldt, Carolina, Verdugo-Rodriguez, Antonio, Borca, Manuel V., Arzt, Jonathan, Rodriguez, Luis L.
Publicada:
29 may 2020
Resumen:
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.
Filiaciones:
Velazquez-Salinas, Lauro:
USDA ARS, Foreign Anim Dis Res Unit, Plum Isl Anim Dis Ctr, Greenport, NY 11944 USA
Univ Nacl Autonoma Mexico, Coll Vet Med & Anim Sci, Mexico City, DF, Mexico
Oak Ridge Inst Sci & Educ, PIADC Res Participat Program, Oak Ridge, TN USA
Pauszek, Steven J.:
USDA ARS, Foreign Anim Dis Res Unit, Plum Isl Anim Dis Ctr, Greenport, NY 11944 USA
Holinka, Lauren G.:
USDA ARS, Foreign Anim Dis Res Unit, Plum Isl Anim Dis Ctr, Greenport, NY 11944 USA
Gladue, Douglas P.:
USDA ARS, Foreign Anim Dis Res Unit, Plum Isl Anim Dis Ctr, Greenport, NY 11944 USA
Rekant, Steven I.:
USDA ARS, Foreign Anim Dis Res Unit, Plum Isl Anim Dis Ctr, Greenport, NY 11944 USA
Oak Ridge Inst Sci & Educ, PIADC Res Participat Program, Oak Ridge, TN USA
Bishop, Elizabeth A.:
USDA ARS, Foreign Anim Dis Res Unit, Plum Isl Anim Dis Ctr, Greenport, NY 11944 USA
Stenfeldt, Carolina:
USDA ARS, Foreign Anim Dis Res Unit, Plum Isl Anim Dis Ctr, Greenport, NY 11944 USA
Univ Minnesota, Dept Vet Populat Med, St Paul, MN 55108 USA
Verdugo-Rodriguez, Antonio:
Univ Nacl Autonoma Mexico, Coll Vet Med & Anim Sci, Mexico City, DF, Mexico
Borca, Manuel V.:
USDA ARS, Foreign Anim Dis Res Unit, Plum Isl Anim Dis Ctr, Greenport, NY 11944 USA
Arzt, Jonathan:
USDA ARS, Foreign Anim Dis Res Unit, Plum Isl Anim Dis Ctr, Greenport, NY 11944 USA
Rodriguez, Luis L.:
USDA ARS, Foreign Anim Dis Res Unit, Plum Isl Anim Dis Ctr, Greenport, NY 11944 USA
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