AUTHOR=Shi Peidian , Su Yanxin , Li Ruiqiao , Zhang Lei , Chen Chen , Zhang Lilin , Faaberg Kay , Huang Jinhai 

TITLE=Dual Regulation of Host TRAIP Post-translation and Nuclear/Plasma Distribution by Porcine Reproductive and Respiratory Syndrome Virus Non-structural Protein 1α Promotes Viral Proliferation

JOURNAL=Frontiers in Immunology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.03023

DOI=10.3389/fimmu.2018.03023

ISSN=1664-3224

ABSTRACT=In this study, we show that porcine reproductive and respiratory syndrome virus (PRRSV) nonstructural protein 1α (nsp1α) 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 nsp1α inhibits small ubiquitin-like modifier self-addition (SUMOylation) and K48-linked polyubiquitination of TRAIP. Modulation of the dual modification of TRAIP by PRRSV nsp1α results in over-enrichment of TRAIP in the cytoplasm. Enrichment of nsp1α-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.