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

Journal Article · · Virology
 [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
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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.

Research Organization:
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
Sponsoring Organization:
USDOE National Nuclear Security Administration (NNSA)
Grant/Contract Number:
AC52-07NA27344
OSTI ID:
1512605
Report Number(s):
LLNL-JRNL--772861; 964039
Journal Information:
Virology, Journal Name: Virology Journal Issue: C Vol. 517; ISSN 0042-6822
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (6)

Expanding the Arterivirus Host Spectrum: Olivier’s Shrew Virus 1, A Novel Arterivirus Discovered in African Giant Shrews journal July 2018
Programmed −2/−1 Ribosomal Frameshifting in Simarteriviruses: an Evolutionarily Conserved Mechanism journal June 2019
Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein 1 Beta Interacts with Nucleoporin 62 To Promote Viral Replication and Immune Evasion journal May 2019
The nsp2 Hypervariable Region of Porcine Reproductive and Respiratory Syndrome Virus Strain JXwn06 Is Associated with Viral Cellular Tropism to Primary Porcine Alveolar Macrophages journal September 2019
A Nanobody Targeting Viral Nonstructural Protein 9 Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication journal November 2018
Programmed -2/-1 Ribosomal Frameshifting in Simarteriviruses: an Evolutionarily Conserved Mechanism. text January 2019

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