SLC25A12 inhibits Japanese encephalitis virus replication by interacting with the NS1 and enhancing the type I interferon response

• Published in: Veterinary microbiology 2024-10, Vol.297, p.110199, Article 110199
• Main Authors: Yin, You-qin, Liu, Le-le, Jiang, Yu-ting, Xing, Jin-chao, Qi, Wen-bao, Huang, Li-hong
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; encephalitis; Encephalitis Virus, Japanese - genetics; Encephalitis Virus, Japanese - immunology; Encephalitis Virus, Japanese - physiology; Encephalitis, Japanese - immunology; Encephalitis, Japanese - virology; family; HEK293 Cells; Host factor; Host-Pathogen Interactions; host-pathogen relationships; Humans; IFN-β; Innate immunity; Interferon Type I - genetics; Interferon Type I - immunology; Interferon Type I - metabolism; Interferon-beta - genetics; Interferon-beta - immunology; Interferon-beta - metabolism; interferons; Japanese encephalitis virus; NS1 protein; RNA; SLC25A12; solutes; Swine; viral nonstructural proteins; Viral Nonstructural Proteins - genetics; Viral Nonstructural Proteins - metabolism; Virus Replication; viruses
• ISSN: 0378-1135; 1873-2542; 1873-2542
• DOI: 10.1016/j.vetmic.2024.110199

Japanese encephalitis virus (JEV) is a mosquito-borne, zoonotic orthoflavivirus causing human encephalitis and reproductive disorders in pigs. Cell-intrinsic antiviral restriction factors are the first line of defense that prevent a virus from establishing a productive infection, while the molecular mechanism of the virus-host interaction is still not fully understood. Our in vitro experiments demonstrated that the Solute Carrier Family 25 Member 12 (SLC25A12) interacted with the JEV nonstructural protein 1 (NS1) and inhibited JEV replication. Furthermore, we showed that knockdown or knockout of SLC25A12 promoted JEV replication, while overexpression of SLC25A12 repressed viral replication. Finally, we demonstrated that SLC25A12 increased IRF7 mRNA levels, which promoted IFN-β expression and subsequently induced antiviral effects. Collectively, our study revealed that SLC25A12 interacted with NS1, inhibiting viral RNA synthesis and transcription and enhancing type I interferon induction for antiviral effects. •SLC25A12 co-localizes and interacts with JEV NS1.•SLC25A12 inhibits JEV infection in HeLa cells.•SLC25A12 positively modulates type I interferon induction by upregulating IRF7 mRNA levels.