{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:57:58Z","timestamp":1791824278217,"version":"4.3.4"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Tianjin Synthetic biotechnology innovation capability improvement project in China","award":["TSBICIP-KJGG-014"],"award-info":[{"award-number":["TSBICIP-KJGG-014"]}]},{"name":"the key underprop project of Tianjin Municipal Science and Technology Bureau","award":["20YFZCSN00340"],"award-info":[{"award-number":["20YFZCSN00340"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Ubiquitination plays a major role in immune regulation after viral infection. An alternatively spliced porcine E3 ubiquitin ligase RNF122 promoted PRRSV infection and upregulated in PRRSV-infected PAM cells was identified. We characterized the core promoter of RNF122, located between \u2212550 to \u2212470 bp upstream of the transcription start site (TSS), which displayed significant differential transcriptional activities in regulating the transcription and expression of RNF122. The transcription factor HLTF was inhibited by nsp1\u03b1 and nsp7 of PRRSV, and the transcription factor E2F complex regulated by nsp9. Together, they modulated the transcription and expression of RNF122. RNF122 could mediate K63-linked ubiquitination to raise stability of PRRSV nsp4 protein and thus promote virus replication. Moreover, RNF122 also performed K27-linked and K48-linked ubiquitination of MDA5 to degrade MDA5 and inhibit IFN production, ultimately promoted virus proliferation. In this study, we illustrate a new immune escape mechanism of PRRSV that enhances self-stability and function of viral nsp4, thus, regulating RNF122 expression to antagonize IFN\u03b1\/\u03b2 production. The present study broadens our knowledge of PRRSV-coding protein modulating transcription, expression and modification of host protein to counteract innate immune signaling, and may provide novel insights for the development of antiviral drugs.<\/jats:p>","DOI":"10.3390\/v14020424","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T08:23:29Z","timestamp":1645431809000},"page":"424","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["PRRSV Non-Structural Proteins Orchestrate Porcine E3 Ubiquitin Ligase RNF122 to Promote PRRSV Proliferation"],"prefix":"10.3390","volume":"14","author":[{"given":"Ruiqi","family":"Sun","sequence":"first","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyu","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqiao","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxuan","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilin","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7104-7223","authenticated-orcid":false,"given":"Jun","family":"Han","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1073-533X","authenticated-orcid":false,"given":"Jinhai","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.2460\/javma.2005.227.385","article-title":"Assessment of the economic impact of porcine reproductive and respiratory syndrome on swine production in the United States","volume":"227","author":"Neumann","year":"2005","journal-title":"J. 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