Porcine reproductive and respiratory syndrome virus nonstructural protein 1β modulates host innate immune response by antagonizing IRF3 activation

Lalit K. Beura, Saumendra N. Sarkar, Byungjoon Kwon, Sakthivel Subramaniam, Clinton Jones, Asit K Pattnaik, Fernando A. Osorio

Research output: Contribution to journalArticle

169 Citations (Scopus)

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) infection of swine leads to a serious disease characterized by a delayed and defective adaptive immune response. It is hypothesized that a suboptimal innate immune response is responsible for the disease pathogenesis. In the study presented here we tested this hypothesis and identified several nonstructural proteins (NSPs) with innate immune evasion properties encoded by the PRRS viral genome. Four of the total ten PRRSV NSPs tested were found to have strong to moderate inhibitory effects on beta interferon (IFN-β) promoter activation. The strongest inhibitory effect was exhibited by NSP1 followed by, NSP2, NSP11, and NSP4. We focused on NSP1α and NSP1β (self-cleavage products of NSP1 during virus infection) and NSP11, three NSPs with strong inhibitory activity. All of three proteins, when expressed stably in cell lines, strongly inhibited double-stranded RNA (dsRNA) signaling pathways. NSP1β was found to inhibit both IFN regulatory factor 3 (IRF3)- and NF-κB-dependent gene induction by dsRNA and Sendai virus. Mechanistically, the dsRNA-induced phosphorylation and nuclear translocation of IRF3 were strongly inhibited by NSP1β. Moreover, when tested in a porcine myelomonocytic cell line, NSP1β inhibited Sendai virus-mediated activation of porcine IFN-β promoter activity. We propose that this NSP1β-mediated subversion of the host innate immune response plays an important role in PRRSV pathogenesis.

Original languageEnglish (US)
Pages (from-to)1574-1584
Number of pages11
JournalJournal of virology
Volume84
Issue number3
DOIs
StatePublished - Feb 1 2010

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Interferon Regulatory Factor-3
Porcine respiratory and reproductive syndrome virus
Porcine reproductive and respiratory syndrome virus
Innate Immunity
Double-Stranded RNA
Sendai virus
Swine
double-stranded RNA
Virus Diseases
swine
Proteins
pathogenesis
proteins
Porcine Reproductive and Respiratory Syndrome
dsRNA viruses
promoter regions
cell lines
interferon-beta
immune evasion
Immune Evasion

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Porcine reproductive and respiratory syndrome virus nonstructural protein 1β modulates host innate immune response by antagonizing IRF3 activation. / Beura, Lalit K.; Sarkar, Saumendra N.; Kwon, Byungjoon; Subramaniam, Sakthivel; Jones, Clinton; Pattnaik, Asit K; Osorio, Fernando A.

In: Journal of virology, Vol. 84, No. 3, 01.02.2010, p. 1574-1584.

Research output: Contribution to journalArticle

Beura, Lalit K. ; Sarkar, Saumendra N. ; Kwon, Byungjoon ; Subramaniam, Sakthivel ; Jones, Clinton ; Pattnaik, Asit K ; Osorio, Fernando A. / Porcine reproductive and respiratory syndrome virus nonstructural protein 1β modulates host innate immune response by antagonizing IRF3 activation. In: Journal of virology. 2010 ; Vol. 84, No. 3. pp. 1574-1584.
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