Middle East respiratory syndrome coronavirus ORF4b protein inhibits TLR7- and TLR9-dependent alpha interferon induction.
FEBS Lett
; 596(19): 2538-2554, 2022 10.
Article
in English
| MEDLINE | ID: covidwho-2007085
ABSTRACT
The Toll-like receptor (TLR)7- and TLR9-dependent signalling cascade is responsible for production of a large amount of alpha interferon by plasmacytoid dendritic cells upon viral infection. Here, we show that Middle East respiratory syndrome coronavirus (MERS-CoV) accessory protein ORF4b has the most potential among the MERS-CoV accessory proteins to inhibit the TLR7/9-signaling-dependent alpha interferon production. ORF4b protein, which has a bipartite nuclear localization signal, was found to bind to IKKα, a kinase responsible for phosphorylation of interferon regulatory factor (IRF)7. This interaction caused relocation of a large proportion of IKKα from the cytoplasm to the nucleus. Studies using ORF4b and IKKα mutants demonstrated that ORF4b protein inhibited IKKα-mediated IRF7 phosphorylation by sequestering IKKα in the nucleus and by impeding the phosphorylation process of cytoplasmic IKKα.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
I-kappa B Kinase
/
Middle East Respiratory Syndrome Coronavirus
Language:
English
Journal:
FEBS Lett
Year:
2022
Document Type:
Article
Affiliation country:
1873-3468.14486
Similar
MEDLINE
...
LILACS
LIS