December 6, 2022

Ana Valero-Rello and Rafael Sanjuán


The cross-species transmission of viruses from wild or domestic animals to humans (zoonosis) has produced major epidemics, but our understanding of this complex process is still very limited. Some risk factors have been identified, such as ecological perturbations and the nature of viral reservoir species. However, it remains unclear how cross-species transmission and zoonosis depend on fundamental viral features. Using large amounts of data released by recent viral discovery initiatives, here we show that enveloped viruses tend to infect more host species and are more likely to cause zoonotic infections than nonenveloped viruses, while other basic viral features examined play less obvious roles. These findings challenge previous views in the field and will help guide viral outbreak surveillance.


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 determine this process as previous work has focused on a few hundred viruses that are not representative of 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. Our analysis reveals that enveloped viruses tend to infect more host species and are more likely to be zoonotic than nonenveloped viruses, while other viral traits such as genome composition, structure, size, or the viral replication compartment play a less obvious role. This contrasts with the previous notion that viral envelopes did not significantly impact or even reduce 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 of receptor-binding proteins and evasion of viral entry barriers.