Pseudorabies virus inhibits type I and type III interferon-induced signaling via proteasomal degradation of Janus kinases

Both type I and III interferons (IFNs) play a crucial role in host antiviral response by activating the JAK/STAT (Janus kinase/signal transducer and activator of transcription) signaling pathway to trigger the expression of antiviral IFN-stimulated genes (ISGs). We report that the porcine alphaherpesvirus pseudorabies virus (PRV) triggers proteasomal degradation of the key Janus kinases Jak1 and to a lesser exent Tyk2, thereby inhibiting both type I and III IFN-induced STAT1 phosphorylation and suppressing IFN-induced expression of ISGs. UV-inactivated PRV did not interfere with IFN signaling. In addition, deletion of the EP0 gene from the PRV genome or inhibition of viral genome replication did not affect PRV-induced inhibition of IFN signaling. To our knowledge, this is the first report describing Janus kinase degradation by alphaherpesviruses. These findings thus reveal a novel alphaherpesvirus evasion mechanism of type I and type III IFNs. IMPORTANCE Type I and III IFNs trigger signaling via Janus kinases that phosphorylate and activate 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 IFNs 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.

Prevalence of Porcine Pseudorabies Virus and Its Coinfection Rate in Heilongjiang Province in China from 2013 to 2018

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Simultaneous detection of porcine pseudorabies virus, porcine parvovirus and porcine circovirus type 2 by multiplex real-time PCR and amplicon melting curve analysis using SYBR Green I

Porcine parvovirus, porcine pseudorabies virus and porcine circovirus type 2 can cause reproductive failure in pigs, and swine are often simultaneously infected by combinations of the three viruses. We here report the development of a SYBR Green I-based multiplex real time PCR assay for simultaneous detection of porcine parvovirus, porcine pseudorabies virus and porcine circovirus type 2. Three pairs of specific primers were designed for the porcine parvovirus-VP2, porcine pseudorabies virus-gH and porcine circovirus type 2-ORF2 genes. Viral genomes were identified based on their distinctive melting temperatures in singleplex PCR reactions. The melting temperature was 74.5 °C for the 313 bp amplicon of porcine parvovirus-VP2 gene, 87.5 °C for the 355 bp amplicon of porcine pseudorabies virus-gH gene and 80.5 °C for the 171 bp amplicon of the porcine circovirus type 2-ORF2 gene, respectively. The detection limit of the method ranged from 0.01–0.03 TCID₅₀/ml for the three viruses. In addition, porcine parvovirus, porcine pseudorabies virus and porcine circovirus type 2 viral loads were measured in 100 field samples, and the result showed that the concordance between real-time PCR and conventional PCR was 60.42%. The sensitivity and specificity of real-time PCR were 100% and 100%, while those of conventional PCR were 40.83% and 72.22%, respectively.