Viral interferon antagonism shapes host tropism

Outbreaks of zoonotic viruses in human populations highlight the need to understand the molecular factors that influence viral host tropism and interspecies transmission. A virus’s host range is determined not only by the expression of host factors that facilitate viral entry and replication, but also by the virus’s ability to evade host antiviral immunity. The interferon (IFN) response is a potent immune defense rapidly mobilized upon viral infections. To overcome this immune barrier and establish infection, viruses continuously evolve evasion strategies. This review illustrates, through a series of examples, how species-specific interactions between viruses and the IFN response erect interspecies barriers. We discuss the necessity to develop cellular models derived from viral reservoir hosts, as well as machine learning approaches, to better grasp species-specific viral sensitivity to the IFN response. These approaches will be essential for understanding viral interspecies transmission and guiding effective pandemic preparedness measures.