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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Virus and Prion Research » Research » Publications at this Location » Publication #355984

Research Project: Intervention Strategies to Control Endemic and New and Emerging Viral Diseases of Swine

Location: Virus and Prion Research

Title: Dual regulation of nuclear/plasma distribution and modification of TRAIP by porcine reproductive and respiratory syndrome virus nonstructural protein 1alpha promotes viral proliferation

item SHI, PEIDIAN - Tianjin University
item SU, YANXIN - Tianjin University
item LI, RUIQIAO - Tianjin University
item ZHANG, LEI - Tianjin University
item CHEN, CHEN - Tianjin University
item ZHANG, LILIN - Tianjin University
item Faaberg, Kay
item HUANG, JINHAI - Tianjin University

Submitted to: Frontiers in Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/6/2018
Publication Date: 12/18/2019
Citation: Shi, P., Su, Y., Li, R., Zhang, L., Chen, C., Zhang, L., Faaberg, K., Huang, J. 2019. Dual regulation of host TRAIP post-translation and nuclear/plasma distribution by porcine reproductive and respiratory syndrome virus non-structural protein 1alpha promotes viral proliferation. Frontiers in Immunology. 9:3023.

Interpretive Summary: Porcine reproductive and respiratory syndrome virus (PRRSV) causes an economically devastating disease and is the most problematic pathogen for swine in the United States. Like many viruses, PRRSV has evolved mechanisms to evade the host's immune system. In this study, we show that PRRSV nonstructural protein 1alpha (nsp1alpha), a protein made by the virus, will alter how the pig's immune system functions. This alteration is to the advantage of the virus and works by nsp1alpha interacting with specific proteins in the pig that normally upregulate the pig's immune response. The viral protein-host protein interaction inhibits the pig’s immune response which gives the virus an advantage and leads to a chronic infection of the pig. Understanding this novel mechanism can provide insight into new ways to develop PRRSV vaccines to aid in the fight against this virus.

Technical Abstract: In this study, we show that porcine reproductive and respiratory syndrome virus (PRRSV) nonstructural protein 1alpha (nsp1alpha) escapes innate immunity and also promotes virus proliferation by modulating nuclear to cytoplasmic translocation and distribution ratio of tumor necrosis factor (TNF) receptor associated factors (TRAF) interacting protein (TRAIP). Mechanistically, PRRSV nsp1alpha inhibits small ubiquitin-like modifier self-addition (SUMOylation) and K48-linked polyubiquitination of TRAIP. Modulation of the dual modification of TRAIP by PRRSV nsp1alpha results in over-enrichment of TRAIP in the cytoplasm. Enrichment of nsp1alpha-induced cytoplasmic TRAIP in turn leads to excessive K48 ubiquitination and degradation of serine/threonine-protein kinase (TBK1), thereby antagonizing TBK1-IRF3-IFN signaling. This study proposes a novel mechanism by which PRRSV utilizes host proteins to regulate innate immunity. Findings from this study provides novel perspective to advance our understanding in the pathogenesis of PRRSV.