Modulation of type I interferon induction by porcine reproductive and respiratory syndrome virus and degradation of CREB-binding protein by non-structural protein 1 in MARC-145 and HeLa cells.
Porcine reproductive and respiratory syndrome (PRRS) is an emerged disease of swine characterized by negligible response of type I IFNs and viral persistence. We show that the PRRSV non-structural protein 1 (Nsp1) is the viral component responsible for modulation of IFN response. Nsp1 blocked dsRNA-induced IRF3 and IFN promoter activities. Nsp1 did not block phosphorylation and nuclear translocation of IRF3 but inhibited IRF3 association with CREB-binding protein (CBP) in the nucleus. While IRF3 was stable, CBP was degraded, and CBP degradation was proteasome-dependent, suggesting that CBP degradation is not due to the protease activity of Nsp1 but an intermediary is involved. Our data suggest that the Nsp1-mediated CBP degradation inhibits the recruitment of CBP for enhanceosome assembly, leading to the block of IFN response. CBP degradation is a novel strategy for viral evasion from the host response, and Nsp1 may form a new class of viral antagonists for IFN modulation.
Kim
Oekyung
O
Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.
Sun
Yan
Y
Lai
Frances W
FW
Song
Cheng
C
Yoo
Dongwan
D
D000818:Animals; D050882:CREB-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000037:antagonists & inhibitors; D007370:Interferon Type I / Q000096:biosynthesis* / Q000276:immunology*; D019316:Porcine respiratory and reproductive syndrome virus / Q000276:immunology* / Q000472:pathogenicity*; D013552:Swine; D017361:Viral Nonstructural Proteins / Q000378:metabolism*
C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D017361:Viral Nonstructural Proteins; D050882:CREB-Binding Protein