Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Oct;596(19):2538-2554.
doi: 10.1002/1873-3468.14486. Epub 2022 Sep 8.

Middle East respiratory syndrome coronavirus ORF4b protein inhibits TLR7- and TLR9-dependent alpha interferon induction

Yoshinori Kitagawa  1 , Takumi Tsukamoto  2 , Masae Itoh  2 , Bin Gotoh  1
Affiliations
Free article

Middle East respiratory syndrome coronavirus ORF4b protein inhibits TLR7- and TLR9-dependent alpha interferon induction

Yoshinori Kitagawa et al. FEBS Lett. 2022 Oct.
Free article

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: IKKα; Middle East respiratory syndrome coronavirus; ORF4b protein; TLR7/9-dependent signalling cascade; accessory proteins; interferon.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

References

    1. Yang Y, Zhang L, Geng H, Deng Y, Huang B, Guo Y, et al. The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists. Protein Cell. 2013;4:951-61.
    1. Matthews KL, Coleman CM, van der Meer Y, Snijder EJ, Frieman MB. The ORF4b-encoded accessory proteins of Middle East respiratory syndrome coronavirus and two related bat coronaviruses localize to the nucleus and inhibit innate immune signalling. J Gen Virol. 2014;95:874-82.
    1. Kehrer T, Garcia-Sastre A, Miorin L. Control of innate immune activation by severe acute respiratory syndrome coronavirus 2 and other coronaviruses. J Interferon Cytokine Res. 2021;41:205-19.
    1. Li JY, Zhou ZJ, Wang Q, He QN, Zhao MY, Qiu Y, et al. Innate immunity evasion strategies of highly pathogenic coronaviruses: SARS-CoV, MERS-CoV, and SARS-CoV-2. Front Microbiol. 2021;12:770656.
    1. Menachery VD, Mitchell HD, Cockrell AS, Gralinski LE, Yount BL Jr, Graham RL, et al. MERS-CoV accessory ORFs play key role for infection and pathogenesis. mBio. 2017;8:e00665-17.

Publication types

MeSH terms

Associated data

LinkOut - more resources