The C proteins of human parainfluenza virus type 1 block IFN signaling by binding and retaining Stat1 in perinuclear aggregates at the late endosome.

PloS One
Henrick SchomackerAlexander Schmidt

Abstract

Interferons (IFNs) play a crucial role in the antiviral immune response. Whereas the C proteins of wild-type human parainfluenza virus type 1 (WT HPIV1) inhibit both IFN-β induction and signaling, a HPIV1 mutant encoding a single amino acid substitution (F170S) in the C proteins is unable to block either host response. Here, signaling downstream of the type 1 IFN receptor was examined in Vero cells to define at what stage WT HPIV1 can block, and F170S HPIV1 fails to block, IFN signaling. WT HPIV1 inhibited phosphorylation of both Stat1 and Stat2, and this inhibition was only slightly reduced for F170S HPIV1. Degradation of Stat1 or Stat2 was not observed. The HPIV1 C proteins were found to accumulate in the perinuclear space, often forming large granules, and co-localized with Stat1 and the cation-independent mannose 6-phosphate receptor (M6PR) that is a marker for late endosomes. Upon stimulation with IFN-β, both the WT and F170S C proteins remained in the perinuclear space, but only the WT C proteins prevented Stat1 translocation to the nucleus. In addition, WT HPIV1 C proteins, but not F170S C proteins, co-immunoprecipitated both phosphorylated and unphosphorylated Stat1. Our findings suggest that the WT HPIV1 C proteins for...Continue Reading

References

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Citations

Nov 24, 2012·Immunology·Kathryne E Taylor, Karen L Mossman
Jun 20, 2012·Current Opinion in Virology·Henrick SchomackerAlexander C Schmidt
Mar 12, 2017·Current Allergy and Asthma Reports·Malgorzata Pawełczyk, Marek Leszek Kowalski
Jul 20, 2018·Viruses·Leonie F ForthMartin Beer
Jul 11, 2014·Journal of Virology·Virginie DoceulDamien Vitour
May 27, 2020·Journal of Immunology Research·Patricio L AcostaLaura B Talarico
Jan 24, 2019·Frontiers in Immunology·Hao-Sen Chiang, Helene Minyi Liu
Jul 10, 2021·Frontiers in Microbiology·Kul Raj RaiJi-Long Chen

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Methods Mentioned

BETA
ubiquitination
confocal microscopy
co-immunoprecipiation
immunoprecipitation
transfection
co-immunoprecipitation
nuclear translocation
PCR
FCS

Clinical Trials Mentioned

NCT00641017

Software Mentioned

Imaris
Alix

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