Ursodeoxycholic acid inhibits feline infectious peritonitis virus infection through activating JAK-STAT signaling pathway-induced type I interferon

Feline infectious peritonitis virus (FIPV), a highly pathogenic subtype of feline coronavirus, is characterized by antigenic variability and immune evasion, resulting in limited efficacy of existing clinical therapeutic regimens. In recent years, ursodeoxycholic acid (UDCA), a hydrophilic bile acid derivative, has been found to have broad Antiviral activity. Based on this, this study significantly improved the replication efficiency of FIPV by constructing a CRFK-PHBLV-N cell line that can stably express the FIPV N protein; UDCA had obvious Antiviral effects, and signaling pathways related to UDCA's anti-FIPV activity were screened by transcriptome Sequencing, and it was found that UDCA could significantly promote secretion of interferon-β by CRFK-PHBLV-N cells, activating the JAK-STAT signaling pathway and upregulating the expression of interferon-stimulated genes. This study revealed that FIPV escapes host immune response by inhibiting the JAK-STAT pathway, and UDCA was able to reverse this inhibition and enhance the expression of Antiviral proteins, thus effectively inhibiting the replication and spread of FIPV. Furthermore, UDCA can also directly disrupt the envelope components of FIPV, inducing the disintegration of the viral structure. This study not only provides a new strategy for the efficient in vitro culture of FIPV, but also lays a theoretical foundation for the development of anti-FIPV drugs targeting the JAK-STAT pathway.

Importance: In this study, through the establishment of a complete research chain of "virus titer-enhanced cell model-drug effect evaluation-signaling pathway analysis", we confirmed that ursodeoxycholic acid (UDCA) can inhibit feline infectious peritonitis virus (FIPV) Infection and revealed that UDCA can activate the JAK-STAT signaling pathway by promoting the production of large amounts of interferon-β in host cells to protect against FIPV Infection. It not only provides a new experimental tool (CRFK-PHBLV-N cell line) and drug candidate (UDCA) for FIP prevention and control, but also lays a theoretical foundation for the development of novel therapeutic strategies targeting the host Antiviral pathway through the elucidation of the JAK-STAT pathway mechanism.