The nonstructural protein 11 of porcine reproductive and respiratory syndrome virus inhibits NF-κB signaling by means of its deubiquitinating activity

Dang Wang, Jinxiu Fan, Liurong Fang, Rui Luo, Haiping Ouyang, Chao Ouyang, Huan Zhang, Huanchun Chen, Kui Li, Shaobo Xiao

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Since its emergence in the late 1980s, porcine reproductive and respiratory syndrome (PRRS) has been devastating the swine industry worldwide. The causative agent is an Arterivirus, referred to as PRRS virus (PRRSV). The pathogenic mechanisms of PRRS are poorly understood, but are believed to correlate with the ability of PRRSV to inhibit immune responses of the host. However, precisely how the virus is capable of doing so remains obscure. In this study, we showed that PRRSV infection led to reduced ubiquitination of cellular proteins. Screening all of the 12 nonstructural proteins (Nsps) encoded by PRRSV revealed that, apart from the Nsp2 which contains the deubiqintinating (DUB) ovarian tumor (OTU) domain, Nsp11, which encodes a unique and conserved endoribonuclease (NendoU) throughout the Nidovirus order, also possesses DUB activity. In vivo assay demonstrated that Nsp11 specifically removed lysine 48 (K48)-linked polyubiquitin chains and the conserved sites C112, H144, D173, K180, and Y219 were critical for its DUB activity. Remarkably, DUB activity was responsible for the capacity of Nsp11 to inhibit nuclear factor κB (NF-κB) activation. Mutations abrogating the DUB activity of Nsp11 toward K48-linked polyubiquitin chains of IκBα nullified the suppressive effect on NF-κB. Our data add Nsp11 to the list of DUBs encoded by PRRSV and uncover a novel mechanism by which PRRSV cripples host innate immune responses.

Original languageEnglish (US)
Pages (from-to)357-366
Number of pages10
JournalMolecular Immunology
Volume68
Issue number2
DOIs
StatePublished - May 6 2015

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Porcine Reproductive and Respiratory Syndrome
Porcine respiratory and reproductive syndrome virus
Viruses
Polyubiquitin
Proteins
Nidovirales
Arterivirus
Endoribonucleases
Ubiquitination
Virus Diseases
Innate Immunity
Lysine
Industry
Swine
Mutation

All Science Journal Classification (ASJC) codes

  • Immunology
  • Molecular Biology

Cite this

The nonstructural protein 11 of porcine reproductive and respiratory syndrome virus inhibits NF-κB signaling by means of its deubiquitinating activity. / Wang, Dang; Fan, Jinxiu; Fang, Liurong; Luo, Rui; Ouyang, Haiping; Ouyang, Chao; Zhang, Huan; Chen, Huanchun; Li, Kui; Xiao, Shaobo.

In: Molecular Immunology, Vol. 68, No. 2, 06.05.2015, p. 357-366.

Research output: Contribution to journalArticle

Wang, Dang ; Fan, Jinxiu ; Fang, Liurong ; Luo, Rui ; Ouyang, Haiping ; Ouyang, Chao ; Zhang, Huan ; Chen, Huanchun ; Li, Kui ; Xiao, Shaobo. / The nonstructural protein 11 of porcine reproductive and respiratory syndrome virus inhibits NF-κB signaling by means of its deubiquitinating activity. In: Molecular Immunology. 2015 ; Vol. 68, No. 2. pp. 357-366.
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