State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, China; Key Laboratory of Zoonoses, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China; National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangzhou 510642, China; Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Guangzhou 510642, China.
Key Laboratory of Zoonoses, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China.
Vet Microbiol. 2024 Oct;297:110199. doi: 10.1016/j.vetmic.2024.110199. Epub 2024 Jul 29.
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.
日本脑炎病毒（JEV）是一种经蚊子传播的正链黄病毒，可引起人类脑炎和猪的生殖障碍。细胞内固有抗病毒限制因子是防止病毒建立有效感染的第一道防线，而病毒-宿主相互作用的分子机制尚不完全清楚。我们的体外实验表明，溶质载体家族 25 成员 12（SLC25A12）与 JEV 非结构蛋白 1（NS1）相互作用并抑制 JEV 复制。此外，我们表明 SLC25A12 的敲低或敲除促进了 JEV 的复制，而 SLC25A12 的过表达抑制了病毒的复制。最后，我们证明 SLC25A12 增加了 IRF7 mRNA 水平，从而促进 IFN-β 的表达，并随后诱导抗病毒作用。总之，我们的研究表明，SLC25A12 与 NS1 相互作用，抑制病毒 RNA 合成和转录，并增强 I 型干扰素诱导以发挥抗病毒作用。
