ID1 通过靶向干扰素通路抑制口蹄疫病毒复制。

ID1 inhibits foot-and-mouth disease virus replication via targeting of interferon pathways.

机构信息

State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.

Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, China.

出版信息

FEBS J. 2021 Jul;288(14):4364-4381. doi: 10.1111/febs.15725. Epub 2021 Feb 12.

DOI:10.1111/febs.15725

PMID:33492759

Abstract

Inhibitor of DNA-binding 1 (ID1) protein has been studied intensively for its functions in tumorigenesis and maintenance of stem cell-like properties, but its roles in virus infection are less understood. In the present study, we have clearly shown that the foot-and-mouth disease virus (FMDV) promotes ID1 degradation via Cdh1-mediated ubiquitination to facilitate its replication. Mechanistic investigations reveal Forkhead Box O1 (FOXO1) as an ID1 partner, which suppresses interferon regulatory factors 3 expression and interferon (IFN) production. Further investigation identified that ID1 suppresses FOXO1 transcription activity through HDAC4-mediated deacetylation, promoting IFN production and antiviral immune response. These studies establish a prominent role for ID1 in suppressing FDMV replication, which may be extended to other viruses.

摘要

DNA 结合抑制因子 1（ID1）蛋白在肿瘤发生和维持干细胞样特性方面的功能已得到深入研究，但它在病毒感染中的作用知之甚少。在本研究中，我们清楚地表明，口蹄疫病毒（FMDV）通过 Cdh1 介导的泛素化促进 ID1 降解，以促进其复制。机制研究揭示 Forkhead Box O1（FOXO1）是 ID1 的伴侣，它抑制干扰素调节因子 3 的表达和干扰素（IFN）的产生。进一步的研究表明，ID1 通过 HDAC4 介导的去乙酰化抑制 FOXO1 的转录活性，从而促进 IFN 的产生和抗病毒免疫反应。这些研究确立了 ID1 在抑制 FMDV 复制中的重要作用，这可能扩展到其他病毒。