{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:55:35Z","timestamp":1785434135350,"version":"3.56.0"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,4,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Porcine reproductive and respiratory syndrome virus (PRRSV) poses a major threat to the swine industry worldwide. The viral matrix (M) protein is essential for virion assembly and infectivity. In this study, we found that the M protein is degraded through the ubiquitin-proteasome system. Immunoprecipitation and mass spectrometry identified the host deubiquitinase OTUB1 as an M-binding partner. Overexpression of OTUB1 increased M protein stability and expression levels, while OTUB1 knockdown promoted M degradation. OTUB1 interacted with the C-terminal ectodomain of the M protein and specifically removed K48-linked ubiquitin chains that target proteins for proteasomal degradation. Mechanistically, a catalytically inactive OTUB1 mutant (C91A) retained the ability to stabilize and deubiquitinate M, while a mutant defective in the non-canonical pathway (D88A) lost this function, indicating that OTUB1 acts primarily by sequestering E2 ubiquitin-conjugating enzymes. Furthermore, we identified UBE2D2 as the specific E2 ubiquitin-conjugating enzyme sequestered by OTUB1 to prevent M protein degradation. Depletion of OTUB1 significantly attenuated PRRSV replication in MARC-145 cells and primary porcine alveolar macrophages. OTUB1 specifically targeted the M protein without stabilizing other PRRSV proteins. Importantly, OTUB1-mediated stabilization was conserved across M proteins from diverse PRRSV strains, including PRRSV-1, PRRSV-2, and emerging NADC30-like and NADC34-like variants. Collectively, our findings revealed a host mechanism exploited by PRRSV to enhance replication and identified OTUB1 as a potential target for antiviral development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>Porcine reproductive and respiratory syndrome (PRRS) poses a substantial threat to global swine production, resulting in major economic losses. The causative agent, PRRS virus (PRRSV), exhibits high genetic variability, which frequently enables it to evade existing vaccine-induced immunity. Our study identifies the host deubiquitinase OTUB1 as a critical factor exploited by PRRSV to stabilize the essential M protein by sequestering the E2 ubiquitin-conjugating enzyme UBE2D2. This mechanism facilitates enhanced viral replication and is conserved across diverse PRRSV strains. Our findings reveal a key host-pathogen interaction and suggest that disrupting OTUB1-mediated stabilization of the M protein may pave the way for novel antiviral strategies against diverse PRRSV variants. This work thus provides a conceptual foundation for future host-directed interventions against this economically significant pathogen.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01868-25","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T13:01:11Z","timestamp":1774962071000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["OTUB1 stabilizes PRRSV matrix protein through a non-canonical deubiquitination mechanism to promote viral replication"],"prefix":"10.1128","volume":"100","author":[{"given":"Benjin","family":"Liu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0515nd386","id-type":"ROR","asserted-by":"publisher"}],"name":"College of Veterinary Medicine, Northeast Agricultural University","place":["Harbin, 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