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Title: Nonstructural proteins nsp2TF and nsp2N of porcine reproductive and respiratory syndrome virus (PRRSV) play important roles in suppressing host innate immune responses

Abstract

Recently, we identified a unique -2/-1 ribosomal frameshift mechanism in PRRSV, which yields two truncated forms of nonstructural protein (nsp) 2 variants, nsp2TF and nsp2N. Here, in vitro expression of individual PRRSV nsp2TF and nsp2N demonstrated their ability to suppress cellular innate immune responses in transfected cells. Two recombinant viruses were further analyzed, in which either nsp2TF was C-terminally truncated (vKO1) or expression of both nsp2TF and nsp2N was knocked out (vKO2). Host cellular mRNA profiling showed that a panel of cellular immune genes, in particular those involved in innate immunity, was upregulated in cells infected with vKO1 and vKO2. Compared to the wild-type virus, vKO1 and vKO2 expedited the IFN-α response and increased NK cell cytotoxicity, and subsequently enhanced T cell immune responses in infected pigs. Here, our data strongly implicate nsp2TF/nsp2N in arteriviral immune evasion and demonstrate that nsp2TF/nsp2N-deficient PRRSV is less capable of counteracting host innate immune responses.

Authors:
 [1];  [1];  [2];  [3];  [3];  [3];  [2];  [4];  [5];  [1]
  1. Kansas State Univ., Manhattan, KS (United States). Kansas State Veterinary Diagnostic Lab., College of Veterinary Medicine, Dept. of Diagnostic Medicine and Pathobiology
  2. The Ohio State Univ., Columbus, OH (United States). Food Animal Health Research Program (FAHRP), Veterinary Preventive Medicine
  3. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Physical & Life Sciences Directorate
  4. Univ. of Cambridge (United Kingdom). Dept. of Pathology
  5. Leiden Univ. Medical Center, Leiden (The Netherlands). Molecular Virology Lab., Dept. of Medical Microbiology
Publication Date:
Research Org.:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org.:
USDOE National Nuclear Security Administration (NNSA)
OSTI Identifier:
1512605
Report Number(s):
LLNL-JRNL-772861
Journal ID: ISSN 0042-6822; 964039
Grant/Contract Number:  
AC52-07NA27344
Resource Type:
Accepted Manuscript
Journal Name:
Virology
Additional Journal Information:
Journal Volume: 517; Journal Issue: C; Journal ID: ISSN 0042-6822
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Li, Y., Shang, P., Shyu, D., Carrillo, C., Naraghi-Arani, P., Jaing, Crystal J., Renukaradhya, G. J., Firth, A. E., Snijder, E. J., and Fang, Y. Nonstructural proteins nsp2TF and nsp2N of porcine reproductive and respiratory syndrome virus (PRRSV) play important roles in suppressing host innate immune responses. United States: N. p., 2018. Web. doi:10.1016/j.virol.2017.12.017.
Li, Y., Shang, P., Shyu, D., Carrillo, C., Naraghi-Arani, P., Jaing, Crystal J., Renukaradhya, G. J., Firth, A. E., Snijder, E. J., & Fang, Y. Nonstructural proteins nsp2TF and nsp2N of porcine reproductive and respiratory syndrome virus (PRRSV) play important roles in suppressing host innate immune responses. United States. doi:10.1016/j.virol.2017.12.017.
Li, Y., Shang, P., Shyu, D., Carrillo, C., Naraghi-Arani, P., Jaing, Crystal J., Renukaradhya, G. J., Firth, A. E., Snijder, E. J., and Fang, Y. Sun . "Nonstructural proteins nsp2TF and nsp2N of porcine reproductive and respiratory syndrome virus (PRRSV) play important roles in suppressing host innate immune responses". United States. doi:10.1016/j.virol.2017.12.017. https://www.osti.gov/servlets/purl/1512605.
@article{osti_1512605,
title = {Nonstructural proteins nsp2TF and nsp2N of porcine reproductive and respiratory syndrome virus (PRRSV) play important roles in suppressing host innate immune responses},
author = {Li, Y. and Shang, P. and Shyu, D. and Carrillo, C. and Naraghi-Arani, P. and Jaing, Crystal J. and Renukaradhya, G. J. and Firth, A. E. and Snijder, E. J. and Fang, Y.},
abstractNote = {Recently, we identified a unique -2/-1 ribosomal frameshift mechanism in PRRSV, which yields two truncated forms of nonstructural protein (nsp) 2 variants, nsp2TF and nsp2N. Here, in vitro expression of individual PRRSV nsp2TF and nsp2N demonstrated their ability to suppress cellular innate immune responses in transfected cells. Two recombinant viruses were further analyzed, in which either nsp2TF was C-terminally truncated (vKO1) or expression of both nsp2TF and nsp2N was knocked out (vKO2). Host cellular mRNA profiling showed that a panel of cellular immune genes, in particular those involved in innate immunity, was upregulated in cells infected with vKO1 and vKO2. Compared to the wild-type virus, vKO1 and vKO2 expedited the IFN-α response and increased NK cell cytotoxicity, and subsequently enhanced T cell immune responses in infected pigs. Here, our data strongly implicate nsp2TF/nsp2N in arteriviral immune evasion and demonstrate that nsp2TF/nsp2N-deficient PRRSV is less capable of counteracting host innate immune responses.},
doi = {10.1016/j.virol.2017.12.017},
journal = {Virology},
number = C,
volume = 517,
place = {United States},
year = {2018},
month = {4}
}

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