Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China; Laboratory Animal Center, Zunyi Medical University, Zunyi, China.
Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
J Biol Chem. 2024 Jan;300(1):105536. doi: 10.1016/j.jbc.2023.105536. Epub 2023 Dec 12.
Porcine deltacoronavirus (PDCoV) is an emerging enteropathogenic coronavirus. It causes mortality in neonatal piglets and is of growing concern because of its broad host range, including humans. To date, the mechanism of PDCoV infection remains poorly understood. Here, based on a genome-wide CRISPR screen of PDCoV-infected cells, we found that HSP90AB1 (heat shock protein 90 alpha family class B1) promotes PDCoV infection. Knockdown or KO of HSP90AB1 in LLC-PK cells resulted in a significantly suppressed PDCoV infection. Infected cells treated with HSP90 inhibitors 17-AAG and VER-82576 also showed a significantly suppressed PDCoV infection, although KW-2478, which does not affect the ATPase activity of HSP90AB1, had no effect on PDCoV infection. We found that HSP90AB1 interacts with the N, NS7, and NSP10 proteins of PDCoV. We further evaluated the interaction between N and HSP90AB1 and found that the C-tail domain of the N protein is the HSP90AB1-interacting domain. Further studies showed that HSP90AB1 protects N protein from degradation via the proteasome pathway. In summary, our results reveal a key role for HSP90AB1 in the mechanism of PDCoV infection and contribute to provide new host targets for PDCoV antiviral research.
猪德尔塔冠状病毒（PDCoV）是一种新兴的肠道致病性冠状病毒。它会导致新生仔猪死亡，由于其广泛的宿主范围，包括人类，因此越来越受到关注。迄今为止，PDCoV 感染的机制仍知之甚少。在这里，我们基于 PDCoV 感染细胞的全基因组 CRISPR 筛选，发现 HSP90AB1（热休克蛋白 90 家族 B1 类）促进了 PDCoV 的感染。在 LLC-PK 细胞中敲低或 KO HSP90AB1 会导致 PDCoV 感染显著受到抑制。用 HSP90 抑制剂 17-AAG 和 VER-82576 处理感染细胞也会导致 PDCoV 感染显著受到抑制，尽管 KW-2478 不影响 HSP90AB1 的 ATP 酶活性，对 PDCoV 感染没有影响。我们发现 HSP90AB1 与 PDCoV 的 N、NS7 和 NSP10 蛋白相互作用。我们进一步评估了 N 和 HSP90AB1 之间的相互作用，发现 N 蛋白的 C 尾结构域是与 HSP90AB1 相互作用的结构域。进一步的研究表明，HSP90AB1 通过蛋白酶体途径保护 N 蛋白免受降解。总之，我们的研究结果揭示了 HSP90AB1 在 PDCoV 感染机制中的关键作用，并为 PDCoV 抗病毒研究提供了新的宿主靶标。
