Membrane proteins with high N-glycosylation, high expression, and multiple interaction partners were preferred by mammalian viruses as receptors

Zhang, Zheng; Zhu, Zhaozhong; Chen, Wenjun; Cai, Zena; Xu, Beibei; Tan, Zhiying; Wu, Aiping; Ge, Xingyi; Guo, Xinhong; Tan, Zhongyang; Xia, Zanxian; Zhu, Haizhen; Jiang, Taijiao; Peng, Yousong

Receptor mediated entry is the first step for viral infection. However, the relationship between viruses and receptors is still obscure. Here, by manually curating a high-quality database of 268 pairs of mammalian virus-host receptor interaction, which included 128 unique viral species or sub-species and 119 virus receptors, we found the viral receptors were structurally and functionally diverse, yet they had several common features when compared to other cell membrane proteins: more protein domains, higher level of N-glycosylation, higher ratio of self-interaction and more interaction partners, and higher expression in most tissues of the host. Additionally, the receptors used by the same virus tended to co-evolve. Further correlation analysis between viral receptors and the tissue and host specificity of the virus shows that the virus receptor similarity was a significant predictor for mammalian virus cross-species. This work could deepen our understanding towards the viral receptor selection and help evaluate the risk of viral zoonotic diseases.