State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.
FASEB J. 2024 Nov 30;38(22):e70187. doi: 10.1096/fj.202400931RR.
African swine fever virus (ASFV) is a large, icosahedral, double-stranded DNA virus in the Asfarviridae family and the causative agent of African swine fever (ASF). ASFV causes a hemorrhagic fever with high mortality rates in domestic and wild pigs. ASFV contains an open reading frame named EP152R, previous research has shown that EP152R is an essential gene for virus rescue in swine macrophages. However, the detailed functions of ASFV EP152R remain elusive. Herein, we demonstrate that EP152R, a membrane protein located in the endoplasmic reticulum (ER), induces ER stress and swelling, triggering the PERK/eIF2α pathway, and broadly inhibiting host protein synthesis in vitro. Additionally, EP152R strongly promotes immune evasion, reduces cell proliferation, and alters cellular metabolism. These results suggest that ASFV EP152R plays a critical role in the intracellular environment, facilitating viral replication. Furthermore, virus-level experiments have shown that the knockdown of EP152R or PERK inhibitors efficiently affects viral replication by decreasing viral gene expression. In summary, these findings reveal a series of novel functions of ASFV EP152R and have important implications for understanding host-pathogen interactions.
非洲猪瘟病毒（ASFV）是一种在 Asfarviridae 科的大型、二十面体、双链 DNA 病毒，也是非洲猪瘟（ASF）的病原体。ASFV 会导致家猪和野猪发生高死亡率的出血性发热。ASFV 包含一个名为 EP152R 的开放阅读框，先前的研究表明，EP152R 是在猪巨噬细胞中拯救病毒所必需的基因。然而，ASFV EP152R 的详细功能仍不清楚。在此，我们证明 EP152R，一种位于内质网（ER）中的膜蛋白，会引发 ER 应激和肿胀，从而触发 PERK/eIF2α 通路，并广泛抑制体外的宿主蛋白合成。此外，EP152R 还能强烈促进免疫逃逸、降低细胞增殖并改变细胞代谢。这些结果表明，ASFV EP152R 在细胞内环境中发挥着关键作用，有助于病毒的复制。此外，病毒水平的实验表明，通过降低病毒基因表达，EP152R 的敲低或 PERK 抑制剂的处理能有效地影响病毒的复制。总之，这些发现揭示了 ASFV EP152R 的一系列新功能，对理解宿主-病原体相互作用具有重要意义。
