Retinoic acid inhibits the infection of porcine reproductive and respiratory syndrome virus.

Abstract

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.