TGEV activates RIG-I/IFN-β/STAT1 axis to promote NLRC5-mediated SLA-I upregulation

Porcine transmissible gastroenteritis virus (TGEV) is a major pathogen causing acute diarrhea and high mortality in neonatal piglets, yet the interplay between TGEV infection and host immune responses, particularly swine leukocyte antigen class I (SLA-I) mediated antigen presentation and type I interferon (IFN) signaling, remains poorly defined. This study aimed to clarify how TGEV modulates SLA-I expression through NOD-like receptor family CARD domain containing 5 (NLRC5) and the underlying signaling pathways. Since TGEV infection was shown to induce SLA-I upregulation in porcine intestinal tissues, we used swine testicular (ST) cells to investigate the expression dynamics of retinoic acid inducible gene I (RIG-I)/IFN-β/signal transducer and activator of transcription 1 (STAT1) axis. TGEV infection significantly upregulated SLA-I and NLRC5 in ST cells, with high expression coinciding with active viral replication, while NLRC5 inhibited TGEV proliferation. Furthermore, TGEV upregulated SLA-I and NLRC5 expression via RIG-I activation, which triggered downstream IFN-β secretion and subsequent STAT1 phosphorylation, thereby facilitating the induction of SLA-I and NLRC5. Moreover, the TGEV open reading frame 7 (ORF7) protein was identified as a critical viral effector contributing to SLA-I and NLRC5 upregulation. Collectively, TGEV infection activates the RIG-I/IFN-β/STAT1 axis to promote NLRC5 mediated SLA-I upregulation, which inhibits TGEV proliferation, elucidating a novel immune regulatory mechanism that balances viral replication and host antiviral defense and providing insights for targeted management strategies against porcine enteric coronaviruses.