Open AccessInducible ATP1B1 Upregulates Antiviral Innate Immune Responses by the Ubiquitination of TRAF3 and TRAF6
Author(s) -
Wei Cao,
Yifei Guo,
Zhikui Cheng,
Gang Xu,
Qi Zuo,
Longyu Nie,
Yu Huang,
Shi Liu,
Ying Zhu
Publication year - 2021
Publication title -
the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.2001262
Subject(s) - innate immune system , proinflammatory cytokine , tank binding kinase 1 , gene knockdown , biology , microbiology and biotechnology , small hairpin rna , immune system , ubiquitin , kinase , nf κb , phosphorylation , rna interference , iκb kinase , rna , signal transduction , immunology , protein kinase a , inflammation , gene , map kinase kinase kinase , genetics
The antiviral innate immune responses are crucial steps during host defense and must be strictly regulated, but the molecular mechanisms of control remain unclear. In this study, we report increased expression of human ATPase Na + /K + ransporting subunit β 1(ATP1B1) after DNA and RNA virus infections. We found that the expression of ATP1B1 can inhibit viral replication and increase the levels of IFNs, IFN-stimulated genes, and inflammatory cytokines. Knockdown of ATP1B1 by specific short hairpin RNA had the opposite effects. Upon viral infection, ATP1B1 was induced, interacted with TRAF3 and TRAF6, and potentiated the ubiquitination of these proteins, leading to increased phosphorylation of downstream molecules, including TGF-β-activated kinase 1 (TAK1) and TANK-binding kinase 1 (TBK1). These results reveal a previously unrecognized role of ATP1B1 in antiviral innate immunity and suggest a novel mechanism for the induction of IFNs and proinflammatory cytokines during viral infection.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom