Evasion of innate antiviral responses by picornavirus security proteins

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.