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The transmission of viruses between different host species is a major source of emerging diseases and is of particular concern in the case of zoonotic transmission from mammals to humans. Several zoonosis risk factors have been identified, but it is currently unclear which viral traits primarily influence this process, as previous work has focused on a few hundred viruses that are not representative of the actual viral diversity. Here we investigate fundamental virological traits that influence cross-species transmissibility and zoonotic propensity by interrogating a database of over 12,000 mammalian virus-host associations, obtained mainly from recent viral metagenomics projects. Our analysis reveals that enveloped viruses tend to infect more host species and are more likely to infect humans than non-enveloped viruses, while other viral traits such as genome composition, structure, size or the viral replication compartment play a minor role. This contrasts with the previous notion that viral envelopes did not significantly impact or even reduced zoonotic risk, and should help better prioritize outbreak prevention efforts. We suggest several mechanisms by which viral envelopes could promote cross-species transmissibility, including structural flexibility and evasion of viral entry barriers.
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