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

Abstract

Receptor mediated entry is the first step for viral infection. There are thousands of cell membrane proteins, yet only a few of them were identified as viral receptors. How the virus selects receptors is an unsolved important question. 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. This work could deepen our understanding towards the viral receptor selection and help for identification of viral receptors.