UBR5 Acts as an Antiviral Host Factor against MERS-CoV via Promoting Ubiquitination and Degradation of ORF4b
Yuzheng Zhou, Rong Zheng, Donglan Liu, Sixu Liu, Cyrollah Disoma, Shiqin Li, Shiqin Li, Yujie Liao, Zongpeng Chen, Ashuai Du, Zijun Dong, Yongxing Zhang, Pinjia Liu, Aroona Razzaq, Dingbin Chen, Xuan Chen, Xiankezi Zhong, Sijie Liu, Siyi Tao, Yuxin Liu, Lunan Xu, Xu Deng, Jia‐Da Li, Taijiao Jiang, Jincun Zhao, Shanni Li, Shanni Li, Zanxian Xia
Abstract
ORF4b was an accessory protein unique to MERS-CoV and was not present in SARS-CoV and SARS-CoV-2 which can also cause severe respiratory disease. Moreover, ORF4b inhibited the production of antiviral cytokines in both the cytoplasm and the nucleus, which was likely to be associated with the high lethality of MERS-CoV. However, whether the host proteins regulate the function of ORF4b is unknown. Our study first determined that UBR5, a host E3 ligase, was a potential host anti-MERS-CoV protein that could reduce the protein level of ORF4b and diminish its anti-immunity ability by inducing ubiquitination and degradation. Based on the discovery of ORF4b-UBR5, a critical molecular target, further increasing the degradation of ORF4b caused by UBR5 could provide a new strategy for the clinical development of drugs for MERS-CoV.