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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]
+ Show Author Affiliations
  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.
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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. https://doi.org/10.1016/j.virol.2017.12.017
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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. https://doi.org/10.1016/j.virol.2017.12.017. https://www.osti.gov/servlets/purl/1512605.
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@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 = {Sun Apr 01 00:00:00 EDT 2018},
month = {Sun Apr 01 00:00:00 EDT 2018}
}
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https://doi.org/10.1016/j.virol.2017.12.017
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Works referenced in this record:

Immune responses in pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV)
journal, February 1998

Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein 1β Modulates Host Innate Immune Response by Antagonizing IRF3 Activation
journal, February 2010

  • Beura, Lalit K.; Sarkar, Saumendra N.; Kwon, Byungjoon
  • Journal of Virology, Vol. 84, Issue 3
  • DOI: 10.1128/JVI.01326-09

Influenza virus-infected dendritic cells stimulate strong proliferative and cytolytic responses from human CD8+ T cells.
journal, August 1994

  • Bhardwaj, N.; Bender, A.; Gonzalez, N.
  • Journal of Clinical Investigation, Vol. 94, Issue 2
  • DOI: 10.1172/JCI117399

Biodegradable nanoparticle delivery of inactivated swine influenza virus vaccine provides heterologous cell-mediated immune response in pigs
journal, February 2017

The PRRSV replicase: Exploring the multifunctionality of an intriguing set of nonstructural proteins
journal, December 2010

Efficient -2 frameshifting by mammalian ribosomes to synthesize an additional arterivirus protein
journal, October 2012

  • Fang, Y.; Treffers, E. E.; Li, Y.
  • Proceedings of the National Academy of Sciences, Vol. 109, Issue 43
  • DOI: 10.1073/pnas.1211145109

Ovarian Tumor Domain-Containing Viral Proteases Evade Ubiquitin- and ISG15-Dependent Innate Immune Responses
journal, December 2007

  • Frias-Staheli, Natalia; Giannakopoulos, Nadia V.; Kikkert, Marjolein
  • Cell Host & Microbe, Vol. 2, Issue 6
  • DOI: 10.1016/j.chom.2007.09.014

Porcine Reproductive and Respiratory Syndrome Virus Utilizes Nanotubes for Intercellular Spread
journal, March 2016

  • Guo, Rui; Katz, Benjamin B.; Tomich, John M.
  • Journal of Virology, Vol. 90, Issue 10
  • DOI: 10.1128/JVI.00036-16

Comparison of the Pathogenicity of Two US Porcine Reproductive and Respiratory Syndrome Virus Isolates with that of the Lelystad Virus
journal, November 1995

The interferon response circuit: Induction and suppression by pathogenic viruses
journal, January 2006

Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists
journal, November 2008

  • Huang, Da Wei; Sherman, Brad T.; Lempicki, Richard A.
  • Nucleic Acids Research, Vol. 37, Issue 1
  • DOI: 10.1093/nar/gkn923

Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
journal, December 2008

  • Huang, Da Wei; Sherman, Brad T.; Lempicki, Richard A.
  • Nature Protocols, Vol. 4, Issue 1
  • DOI: 10.1038/nprot.2008.211

Control of adaptive immunity by the innate immune system
journal, March 2015

  • Iwasaki, Akiko; Medzhitov, Ruslan
  • Nature Immunology, Vol. 16, Issue 4
  • DOI: 10.1038/ni.3123

Innate Control of Adaptive Immunity: Beyond the Three-Signal Paradigm
journal, May 2017

The viral innate immune antagonism and an alternative vaccine design for PRRS virus
journal, September 2017

Ultrastructural Characterization of Arterivirus Replication Structures: Reshaping the Endoplasmic Reticulum To Accommodate Viral RNA Synthesis
journal, December 2011

  • Knoops, K.; Barcena, M.; Limpens, R. W. A. L.
  • Journal of Virology, Vol. 86, Issue 5
  • DOI: 10.1128/JVI.06677-11

Reorganization and expansion of the nidoviral family Arteriviridae
journal, November 2015

A novel flow cytometric assay for quantitation and multiparametric characterization of cell-mediated cytotoxicity
journal, July 2001

Identification of porcine reproductive and respiratory syndrome virus ORF1a-encoded non-structural proteins in virus-infected cells
journal, April 2012

  • Li, Yanhua; Tas, Ali; Snijder, Eric J.
  • Journal of General Virology, Vol. 93, Issue 4
  • DOI: 10.1099/vir.0.039289-0

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV): Pathogenesis and Interaction with the Immune System
journal, February 2016

Interferon type I response in porcine reproductive and respiratory syndrome virus-infected MARC-145 cells
journal, August 2004

A novel role for poly(C) binding proteins in programmed ribosomal frameshifting
journal, June 2016

  • Napthine, Sawsan; Treffers, Emmely E.; Bell, Susanne
  • Nucleic Acids Research, Vol. 44, Issue 12
  • DOI: 10.1093/nar/gkw480

Differentiation of U.S. and European isolates of porcine reproductive and respiratory syndrome virus by monoclonal antibodies.
journal, January 1993

Advances in anti-viral immune defence: revealing the importance of the IFN JAK/STAT pathway
journal, April 2017

  • Raftery, Nicola; Stevenson, Nigel J.
  • Cellular and Molecular Life Sciences, Vol. 74, Issue 14
  • DOI: 10.1007/s00018-017-2520-2

Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures
journal, January 2008

A Simple Method of Estimating Fifty per cent Endpoints12
journal, May 1938

Interferon-stimulated genes and their antiviral effector functions
journal, December 2011

The ontogeny of the porcine immune system
journal, March 2009

Arterivirus molecular biology and pathogenesis
journal, October 2013

  • Snijder, Eric J.; Kikkert, Marjolein; Fang, Ying
  • Journal of General Virology, Vol. 94, Issue 10
  • DOI: 10.1099/vir.0.056341-0

STRING v10: protein–protein interaction networks, integrated over the tree of life
journal, October 2014

  • Szklarczyk, Damian; Franceschini, Andrea; Wyder, Stefan
  • Nucleic Acids Research, Vol. 43, Issue D1
  • DOI: 10.1093/nar/gku1003

Phenotypic maturation of porcine NK- and T-cell subsets
journal, May 2013

  • Talker, Stephanie C.; Käser, Tobias; Reutner, Katharina
  • Developmental & Comparative Immunology, Vol. 40, Issue 1
  • DOI: 10.1016/j.dci.2013.01.003

Arterivirus and Nairovirus Ovarian Tumor Domain-Containing Deubiquitinases Target Activated RIG-I To Control Innate Immune Signaling
journal, November 2011

  • van Kasteren, P. B.; Beugeling, C.; Ninaber, D. K.
  • Journal of Virology, Vol. 86, Issue 2
  • DOI: 10.1128/JVI.06277-11

Differential production of proinflammatory cytokines in the pig lung during different respiratory virus infections: correlations with pathogenicity
journal, August 1999

  • Van Reeth, K.; Labarque, G.; Nauwynck, H.
  • Research in Veterinary Science, Vol. 67, Issue 1
  • DOI: 10.1053/rvsc.1998.0277

Viral tricks to grid-lock the type I interferon system
journal, August 2010

Autocrine Amplification of Type I Interferon Gene Expression Mediated by Interferon Stimulated Gene Factor 3 (ISGF3)
journal, July 1996

Laboratory Investigation of PRRS Virus Infection in Three Swine Herds
journal, October 1993

  • Zeman, D.; Neiger, R.; Yaeger, M.
  • Journal of Veterinary Diagnostic Investigation, Vol. 5, Issue 4
  • DOI: 10.1177/104063879300500404
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    Expanding the Arterivirus Host Spectrum: Olivier’s Shrew Virus 1, A Novel Arterivirus Discovered in African Giant Shrews
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    • DOI: 10.1128/jvi.01888-18

    Programmed −2/−1 Ribosomal Frameshifting in Simarteriviruses: an Evolutionarily Conserved Mechanism
    journal, June 2019

    • Li, Yanhua; Firth, Andrew E.; Brierley, Ian
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    • Li, Yanhua; Firth, Andrew; Brierley, Ian
    • Apollo - University of Cambridge Repository
    • DOI: 10.17863/cam.40421
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