Cellular receptors for mammalian viruses

The interaction of viral surface components with cellular receptors and other entry factors determines key features of viral infection such as host range, tropism and virulence. Despite intensive research, our understanding of these interactions remains limited. Here, we report a systematic analysis of published work on mammalian virus receptors and attachment factors. We build a dataset twice the size of those available to date and specify the role of each factor in virus entry. We identify cellular proteins that are preferentially used as virus receptors, which tend to be plasma membrane proteins with a high propensity to interact with other proteins. Using machine learning, we assign cell surface proteins a score that predicts their ability to function as virus receptors. Our results also reveal common patterns of receptor usage among viruses and suggest that enveloped viruses tend to use a broader repertoire of alternative receptors than non-enveloped viruses, a feature that might confer them with higher interspecies transmissibility. Specific interactions between viruses and cellular entry factors are a critical initial step in viral infection. The identification of virus receptors and other key entry factors is important for understanding viral tropism, pathogenesis and cross-species transmissibility, as well as for the design of antiviral drugs. Here, we provide a comprehensive meta-analysis of our current knowledge of virus receptors and attachment factors. We use the newly assembled dataset to reveal general patterns of receptor use across viruses and to derive predictions about the propensity of each cell surface protein to serve as a virus receptor. This work may assist future research on receptor discoveries, and suggests new implications of virus-receptor interactions, including viral emergence.