Porcine epidemic diarrhea virus (PEDV) causes diarrhea and dehydration in pigs and leads to great economic losses in the commercial swine industry. However, the underlying molecular mechanisms of host response to viral infection remain unclear. In the present study, we investigated a novel mechanism by which RALY, a member of the heterogeneous nuclear ribonucleoprotein family, significantly promotes the degradation of the PEDV nucleocapsid (N) protein to inhibit viral replication. Furthermore, we identified an interaction between RALY and the E3 ubiquitin ligase MARCH8 (membrane-associated RING-CH 8), as well as the cargo receptor NDP52 (nuclear dot protein 52 kDa), suggesting that RALY could suppress PEDV replication by degrading the viral N protein through a RALY–MARCH8–NDP52–autophagosome pathway. Collectively, these results suggest a preventive role of RALY against PEDV infection via the autophagy pathway and open up the possibility of inducing RALY in vivo as an effective prophylactic and preventive treatment for PEDV infection.

猪流行性腹泻病毒（PEDV）引起猪腹泻和脱水，给商业养猪业带来巨大的经济损失。然而，宿主对病毒感染反应的潜在分子机制仍不清楚。在本研究中，我们研究了一种新的机制，通过该机制，异质核核糖核蛋白家族的成员 RALY 显着促进 PEDV 核衣壳 (N) 蛋白的降解以抑制病毒复制。此外，我们确定了 RALY 与 E3 泛素连接酶 MARCH8（膜相关 RING-CH 8）以及货物受体 NDP52（核点蛋白 52 kDa）之间的相互作用，表明 RALY 可以通过降解病毒来抑制 PEDV 复制N 蛋白通过 RALY-MARCH8-NDP52-自噬体途径。集体，通过自噬途径，并开辟了在体内诱导 RALY作为 PEDV 感染的有效预防和预防治疗的可能性。