PMID- 30619364 OWN - NLM STAT- MEDLINE DCOM- 20191125 LR - 20200309 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 9 DP - 2018 TI - 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. PG - 3023 LID - 10.3389/fimmu.2018.03023 [doi] LID - 3023 AB - In this study, we show that porcine reproductive and respiratory syndrome virus (PRRSV) non-structural protein 1alpha (nsp1alpha) facilitates PRRSV escape from innate immune by modulating nuclear to cytoplasmic translocation and distribution ratio of TRAIP to promote virus proliferation. Mechanistically, TRAIP interacts with PRRSV nsp1alpha via its K205 site, while NSP1alpha decreases the SUMOylation and K48 ubiquitination independent of the TRAIP interaction K205 site. 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. FAU - Shi, Peidian AU - Shi P AD - School of Life Sciences, Tianjin University, Tianjin, China. FAU - Su, Yanxin AU - Su Y AD - School of Life Sciences, Tianjin University, Tianjin, China. FAU - Li, Ruiqiao AU - Li R AD - School of Life Sciences, Tianjin University, Tianjin, China. FAU - Zhang, Lei AU - Zhang L AD - School of Life Sciences, Tianjin University, Tianjin, China. FAU - Chen, Chen AU - Chen C AD - School of Life Sciences, Tianjin University, Tianjin, China. FAU - Zhang, Lilin AU - Zhang L AD - School of Life Sciences, Tianjin University, Tianjin, China. FAU - Faaberg, Kay AU - Faaberg K AD - Agricultural Research Service, USDA, National Animal Disease Center, Ames, IA, United States. FAU - Huang, Jinhai AU - Huang J AD - School of Life Sciences, Tianjin University, Tianjin, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181218 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Interferon Type I) RN - 0 (RNA, Small Interfering) RN - 0 (Viral Nonstructural Proteins) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM MH - Animals MH - Cell Nucleus/metabolism MH - Cytoplasm/metabolism MH - HEK293 Cells MH - HeLa Cells MH - Host-Pathogen Interactions/*immunology MH - Humans MH - Immunity, Innate MH - Interferon Type I/immunology/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Porcine Reproductive and Respiratory Syndrome/*immunology/virology MH - Porcine respiratory and reproductive syndrome virus/*immunology/pathogenicity MH - RNA, Small Interfering/metabolism MH - Sus scrofa MH - Swine MH - Ubiquitin-Protein Ligases/genetics/*metabolism MH - Ubiquitination/immunology MH - Viral Nonstructural Proteins/*immunology MH - Virus Replication/immunology PMC - PMC6305329 OTO - NOTNLM OT - IFN OT - PRRSV OT - SUMOylation OT - TBK1 OT - TRAIP OT - nsp1alpha EDAT- 2019/01/09 06:00 MHDA- 2019/11/26 06:00 PMCR- 2018/01/01 CRDT- 2019/01/09 06:00 PHST- 2018/09/21 00:00 [received] PHST- 2018/12/06 00:00 [accepted] PHST- 2019/01/09 06:00 [entrez] PHST- 2019/01/09 06:00 [pubmed] PHST- 2019/11/26 06:00 [medline] PHST- 2018/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2018.03023 [doi] PST - epublish SO - Front Immunol. 2018 Dec 18;9:3023. doi: 10.3389/fimmu.2018.03023. eCollection 2018.