Classical swine fever virus npro limits type I interferon induction in plasmacytoid dendritic cells by interacting with interferon regulatory factor 7
Résumé
Viruses are detected by different classes of pattern recognition receptors that lead to the activation of
interferon regulatory factors (IRF) and consequently to the induction of alpha/beta interferon (IFN-/). In
turn, efficient viral strategies to escape the type I IFN-induced antiviral mechanisms have evolved. Previous
studies established that pestivirus Npro antagonizes the early innate immune response by targeting the
transcription factor IRF3 for proteasomal degradation. Here, we report that Npro of classical swine fever virus
(CSFV) interacts also with IRF7, another mediator of type I IFN induction. We demonstrate that the Znbinding
domain of Npro is essential for the interaction of Npro with IRF7. For IRF3 and IRF7, the DNA-binding
domain, the central region, and most of the regulatory domain are required for the interaction with Npro.
Importantly, the induction of IRF7-dependent type I IFN responses in plasmacytoid dendritic cells (pDC) is
reduced after wild-type CSFV infection compared with infection with virus mutants unable to interact with
IRF7. This is associated with lower levels of IRF7 in pDC. Consequently, wild-type but not Npro mutant
CSFV-infected pDC show reduced responses to other stimuli. Taken together, the results of this study show
that CSFV Npro is capable of manipulating the function of IRF7 in pDC and provides the virus with an
additional strategy to circumvent the innate defense.
Domaines
Sciences du Vivant [q-bio]
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Fiebach 2011_{0063EA0D-8EB2-473B-9E20-19D9DA44C906}.pdf (1.6 Mo)
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