Evasion of innate antiviral responses by picornavirus security proteins

Abstract

The Picornaviridae are a large virus family consisting of 47 genera and 110 species and amongst these viruses are several human and veterinary pathogens. Viral infection is recognized by the host and triggers an antiviral response, which is centered around the production of type I interferons and the antiviral effects of interferon stimulated genes (ISGs). Meanwhile, viruses try to evade the antiviral effects of this response. Picornaviruses are known to predominantly depend on their security proteins (2A and L) to evade antiviral responses, although many of the underlying molecular mechanisms remain to be elucidated. In this thesis, we studied how several picornaviruses evade the induction of type I interferons and the antiviral activities of the ISG PKR. PKR acts as a dsRNA sensor and activator of the cellular stress response. In chapter 2-4 we studied the mechanisms employed by foot-and-mouth disease virus to evade the induction of type I interferons and the cellular stress response. In chapter 5 we investigated how enteroviruses suppress both antiviral pathways and in chapter 6 we explored how kobuviruses evade the cellular stress response.

Full scientific summary can be found on p. 186-189.