Parainfluenza Virus 3 Blocks Antiviral Mediators Downstream of the Interferon Lambda Receptor by Modulating Stat1 Phosphorylation

• DOI: 10.1128/jvi.02502-15
• Publication Date: 2015-12-31T02:54:03Z
• Authors: Kirsten C. Eberle; Jodi L. McGill; Timothy A. Reinhardt; Randy E. Sacco
• Keywords: Vero cell; STAT1; STAT2

ABSTRACT Parainfluenza viruses are known to inhibit type I interferon (IFN) production; however, there is a lack of information regarding the III IFN response during infection. Type IFNs signal through unique heterodimeric receptor, IFN-λR1/interleukin-10R2 (IL-10R2), which primarily expressed by epithelial cells. virus 3 (PIV-3) infection highly restricted airway epithelium. We therefore sought examine signaling pathways PIV-3 used three strains PIV-3: human (HPIV-3), bovine (BPIV-3), and dolphin PIV-1 ( Tursiops truncatus PIV-1, or TtPIV-1). Here, we show that message levels IL-29 significantly increased infection, yet downstream antiviral molecules not upregulated similar those positive control. Furthermore, in Vero cells infected with PIV-3, stimulation recombinant IL-29/-28A/-28B does cause upregulation molecules, suggesting interferes JAK/STAT pathway IFN-λR1/IL-10R2 receptor. Western blotting phosphorylation Stat1 Stat2 bronchial cell line BEAS-2B. In cells, observed reduced serine 727 (S727) site on Stat1, while BEAS-2B was decreased at tyrosine 701 (Y701) These data provide new evidence strategies employed parainfluenza effectively circumvent respiratory cell-specific immunity. IMPORTANCE (PIV) humans associated bronchiolitis pneumonia can be especially problematic infants elderly. Also seen cattle, causes infections young calves. addition, one number pathogens contribute disease complex (BRDC). As their name suggests, interferons (IFNs) produced interfere viral replication. Paramyxoviruses have previously been shown block production IFNs. For first time, it here induce protective primary However, found modulates receptor several specific aid productive response. Importantly, this work expands our understanding how evades host innate