{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T08:58:49Z","timestamp":1774342729030,"version":"3.50.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen threatening the global swine industry, with existing vaccines failing to provide broad protection due to the high viral genetic variability and immune evasion capacity. Retinoic acid (RA), a vitamin A metabolite known for immunomodulatory functions, has been reported to enhance antiviral innate immunity and suppress excessive inflammation. However, whether RA affects PRRSV infection remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The antiviral efficacy of all-trans retinoic acid (ATRA), the major biologically active form of RA, against PRRSV infection was evaluated in both MARC-145 cells and primary porcine alveolar macrophages (PAMs). Furthermore, transcriptomic profiling was conducted to investigate the regulatory effects of ATRA on uninfected and PRRSV-infected PAMs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ATRA significantly inhibited PRRSV infection and replication with minimal cytotoxicity. Transcriptomic profiling revealed that ATRA upregulated basal immune signaling and metabolic transport pathways while suppressing non-specific inflammatory activity in uninfected PAMs. Interestingly, comparative transcriptomics revealed that PRRSV infection led to hyperinflammatory responses and disrupted lipid homeostasis in PAMs, while ATRA treatment reversed these alterations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our findings elucidate that RA exerts antiviral effects against PRRSV through a dual mechanism of attenuating excessive inflammation and restoring cellular metabolic homeostasis, highlighting its potential as an immunomodulatory agent for viral infection control.<\/jats:p>\n                  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