Key result
Pseudorabies virus inhibits both type I and III interferon signaling pathways by triggering proteasome-dependent degradation of Jak1 and Tyk2, suppressing STAT1 phosphorylation and ISG expression.
Why the study?
Viruses have evolved mechanisms to evade host antiviral type I and III interferon signaling, but alphaherpesvirus evasion of type III interferon-mediated signaling was not well addressed.
PRV evades host antiviral responses by triggering proteasomal degradation of Janus kinases, revealing a novel alphaherpesvirus evasion mechanism against type I and III interferons.
Identifies a novel alphaherpesvirus evasion mechanism in animal models; leaves open relevance to human IFN signaling and antiviral strategies.
Type I and III interferons (IFNs) trigger signaling via Janus kinases that phosphorylate and activate signal transducer and activator of transcription (STAT) transcription factors, leading to the expression of antiviral interferon-stimulated genes (ISGs) that result in an antiviral state of host cells. Viruses have evolved various mechanisms to evade this response. Our results indicate that an alphaherpesvirus, the porcine pseudorabies virus (PRV), inhibits both type I and III IFN signaling pathways by triggering proteasome-dependent degradation of the key Janus kinases Jak1 and Tyk2 and consequent inhibition of STAT1 phosphorylation and suppression of ISG expression. Moreover, we found that this inhibition is not caused by incoming virions and does not depend on expression of the viral EP0 protein or viral true late proteins. These data for the first time address alphaherpesvirus evasion of type III IFN-mediated signaling and reveal a previously uncharacterized alphaherpesvirus mechanism of IFN evasion via proteasomal degradation of Janus kinases.
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Yin et al. (2021) studied Pseudorabies virus infection (in vitro). Pseudorabies virus (PRV) infection vs. Mock infection was evaluated on STAT1 phosphorylation and Jak1/Tyk2 protein levels. Pseudorabies virus inhibits both type I and III interferon signaling pathways by triggering proteasome-dependent degradation of Jak1 and Tyk2, suppressing STAT1 phosphorylation and ISG expression.
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