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

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.