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
In this study, we show that porcine reproductive and respiratory syndrome virus (PRRSV) non-structural protein 1α (nsp1α) facilitates PRRSV escape from innate immune by modulating nuclear to cytoplasmic translocation and distribution ratio of TRAIP to promote virus proliferation. Mechanistically, TR...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-12-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.03023/full |
| _version_ | 1819132502014427136 |
|---|---|
| author | Peidian Shi Yanxin Su Ruiqiao Li Lei Zhang Chen Chen Lilin Zhang Kay Faaberg Jinhai Huang |
| author_facet | Peidian Shi Yanxin Su Ruiqiao Li Lei Zhang Chen Chen Lilin Zhang Kay Faaberg Jinhai Huang |
| author_sort | Peidian Shi |
| collection | DOAJ |
| description | In this study, we show that porcine reproductive and respiratory syndrome virus (PRRSV) non-structural protein 1α (nsp1α) 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 nsp1α via its K205 site, while NSP1α decreases the SUMOylation and K48 ubiquitination independent of the TRAIP interaction K205 site. 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. |
| first_indexed | 2024-12-22T09:32:25Z |
| format | Article |
| id | doaj.art-4177cec4bc8b4d60a46a851dd0e05172 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T09:32:25Z |
| publishDate | 2018-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4177cec4bc8b4d60a46a851dd0e051722022-12-21T18:30:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-12-01910.3389/fimmu.2018.03023426234Dual Regulation of Host TRAIP Post-translation and Nuclear/Plasma Distribution by Porcine Reproductive and Respiratory Syndrome Virus Non-structural Protein 1α Promotes Viral ProliferationPeidian Shi0Yanxin Su1Ruiqiao Li2Lei Zhang3Chen Chen4Lilin Zhang5Kay Faaberg6Jinhai Huang7School of Life Sciences, Tianjin University, Tianjin, ChinaSchool of Life Sciences, Tianjin University, Tianjin, ChinaSchool of Life Sciences, Tianjin University, Tianjin, ChinaSchool of Life Sciences, Tianjin University, Tianjin, ChinaSchool of Life Sciences, Tianjin University, Tianjin, ChinaSchool of Life Sciences, Tianjin University, Tianjin, ChinaAgricultural Research Service, USDA, National Animal Disease Center, Ames, IA, United StatesSchool of Life Sciences, Tianjin University, Tianjin, ChinaIn this study, we show that porcine reproductive and respiratory syndrome virus (PRRSV) non-structural protein 1α (nsp1α) 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 nsp1α via its K205 site, while NSP1α decreases the SUMOylation and K48 ubiquitination independent of the TRAIP interaction K205 site. 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.https://www.frontiersin.org/article/10.3389/fimmu.2018.03023/fullPRRSVTRAIPnsp1αSUMOylationIFNTBK1 |
| spellingShingle | Peidian Shi Yanxin Su Ruiqiao Li Lei Zhang Chen Chen Lilin Zhang Kay Faaberg Jinhai Huang 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 Frontiers in Immunology PRRSV TRAIP nsp1α SUMOylation IFN TBK1 |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | PRRSV TRAIP nsp1α SUMOylation IFN TBK1 |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.03023/full |
| work_keys_str_mv | AT peidianshi dualregulationofhosttraipposttranslationandnuclearplasmadistributionbyporcinereproductiveandrespiratorysyndromevirusnonstructuralprotein1apromotesviralproliferation AT yanxinsu dualregulationofhosttraipposttranslationandnuclearplasmadistributionbyporcinereproductiveandrespiratorysyndromevirusnonstructuralprotein1apromotesviralproliferation AT ruiqiaoli dualregulationofhosttraipposttranslationandnuclearplasmadistributionbyporcinereproductiveandrespiratorysyndromevirusnonstructuralprotein1apromotesviralproliferation AT leizhang dualregulationofhosttraipposttranslationandnuclearplasmadistributionbyporcinereproductiveandrespiratorysyndromevirusnonstructuralprotein1apromotesviralproliferation AT chenchen dualregulationofhosttraipposttranslationandnuclearplasmadistributionbyporcinereproductiveandrespiratorysyndromevirusnonstructuralprotein1apromotesviralproliferation AT lilinzhang dualregulationofhosttraipposttranslationandnuclearplasmadistributionbyporcinereproductiveandrespiratorysyndromevirusnonstructuralprotein1apromotesviralproliferation AT kayfaaberg dualregulationofhosttraipposttranslationandnuclearplasmadistributionbyporcinereproductiveandrespiratorysyndromevirusnonstructuralprotein1apromotesviralproliferation AT jinhaihuang dualregulationofhosttraipposttranslationandnuclearplasmadistributionbyporcinereproductiveandrespiratorysyndromevirusnonstructuralprotein1apromotesviralproliferation |