Title: 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

Abstract

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 correlationmore » 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.« less

Authors:

Velazquez-Salinas, Lauro ^[1]; Pauszek, Steven J. ^[2]; Holinka, Lauren G. ^[2]; Gladue, Douglas P. ^[2]; Rekant, Steven I. ^[3]; Bishop, Elizabeth A. ^[2]; Stenfeldt, Carolina ^[4]; Verdugo-Rodriguez, Antonio ^[5]; Borca, Manuel V. ^[2]; Arzt, Jonathan ^[2]; Rodriguez, Luis L. ^[2]

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+ Show Author Affiliations

1. US Dept. of Homeland Security (DHS), Greenport, NY (United States). Plum Island Animal Disease Center. Foreign Animal Disease Research Unit; National Autonomous Univ. of Mexico, Mexico City (Mexico). College of Veterinary Medicine and Animal Science; Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States). PIADC Research Participation Program
2. US Dept. of Homeland Security (DHS), Greenport, NY (United States). Plum Island Animal Disease Center. Foreign Animal Disease Research Unit
3. US Dept. of Homeland Security (DHS), Greenport, NY (United States). Plum Island Animal Disease Center. Foreign Animal Disease Research Unit; Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States). PIADC Research Participation Program
4. US Dept. of Homeland Security (DHS), Greenport, NY (United States). Plum Island Animal Disease Center. Foreign Animal Disease Research Unit; Univ. of Minnesota, Saint Paul, MN (United States). Dept. of Veterinary Population Medicine
5. National Autonomous Univ. of Mexico, Mexico City (Mexico). College of Veterinary Medicine and Animal Science

Publication Date:

Fri May 29 00:00:00 EDT 2020

Research Org.:

Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Org.:

USDOE Office of Science (SC)

OSTI Identifier:

1816400

Grant/Contract Number:  

SC0014664

Resource Type:

Accepted Manuscript

Journal Name:

Frontiers in Microbiology

Additional Journal Information:

Journal Volume: 11; Journal ID: ISSN 1664-302X

Publisher:

Frontiers Research Foundation

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES; vesicular stomatitis; pathogenesis; M51R; virulence; macrophages; immune response; type 1 interferon