Skip to main content
ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Ruminant Diseases and Immunology Research » Research » Publications at this Location » Publication #322166
Title: Parainfluenza virus 3 blocks antiviral mediators downstream of the interferon lambda receptor by modulating stat1 phosphorylation

Author
item EBERLE, KIRSTEN - Iowa State University
item McGill, Jodi
item Reinhardt, Timothy
item Sacco, Randy

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/22/2015
Publication Date: 3/3/2016
Publication URL: http://handle.nal.usda.gov/10113/62943
Citation: Eberle, K.C., McGill, J.L., Reinhardt, T.A., Sacco, R.E. 2016. Parainfluenza virus 3 blocks antiviral mediators downstream of the interferon lambda receptor by modulating stat1 phosphorylation. Journal of Virology. 90:2948-2958. doi:10.1128/JVI.02502-15.

Interpretive Summary: A virus was isolated from a bottlenose dolphin with cold-like symptoms. It was found that this virus was closely related to similar viruses from human and cattle. When cells become infected with a virus, they try to eliminate the virus by inducing what is called an antiviral response. In the present paper, we show how these viruses from humans, dolphins and cattle alter one of the antiviral responses initiated in respiratory cells. Because there is no effective vaccine for this virus, our results provide new information that could lead to new ways to treat this virus.

Technical Abstract: Paramyxoviruses are known to inhibit type I interferon (IFN) production, however there is a lack of information regarding the type III IFN response during infection. Type III IFNs signal through a unique heterodimeric receptor, the IFN-'R1/IL-10R2, which is primarily expressed by epithelial cells. Parainfluenza virus type 3 (PIV-3) infection is highly restricted to the airway epithelium. We therefore sought to examine type III IFN signaling pathways during PIV-3 infection. We used three strains of PIV-3: human PIV-3 (HPIV-3), bovine PIV-3 (BPIV-3), and dolphin PIV-1 (TtPIV-1). Here we show that message levels of IL-29 are significantly increased during PIV-3 infection, yet downstream antiviral signaling molecules are not upregulated to levels similar to the positive control. Furthermore, in Vero cells infected with PIV-3, stimulation with recombinant IL-29/28A/28B does not cause upregulation of downstream antiviral molecules, suggesting that PIV-3 interferes with the JAK/STAT pathway downstream of the IFN-'R1/IL-10R2 receptor. We used western blotting to examine the phosphorylation of Stat1 and Stat2 in Vero and BEAS-2B cells. In Vero cells we observed reduced phosphorylation of the serine 727 (S727) site on Stat1, while in BEAS-2B cells Stat1 was dephosphorylated at the tyrosine 701 (Y701) site during PIV-3 infection. PIV-3 therefore interferes with the phosphorylation of Stat1 downstream of the type III IFN receptor. It is important to examine PIV-3 infection of epithelial cells at the molecular level to aid in development of a successful vaccine. This data provides novel evidence regarding strategies employed by parainfluenza viruses to effectively evade respiratory epithelial cell antiviral immunity.