Home > Research > Publications & Outputs > Poxvirus targeting of E3 ligase β-TrCP by molec...

Research

Associated organisational unit

Links

Text available via DOI:

Keywords

View graph of relations

Poxvirus targeting of E3 ligase β-TrCP by molecular mimicry: a mechanism to inhibit NF-κB activation and promote immune evasion and virulence

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Published

Standard

Poxvirus targeting of E3 ligase β-TrCP by molecular mimicry: a mechanism to inhibit NF-κB activation and promote immune evasion and virulence. / Mansur, Daniel S.; Maluquer de Motes, Carlos; Unterholzner, Leonie et al.
In: PLoS Pathogens, Vol. 9, No. 2, e1003183, 02.2013.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Mansur, DS, Maluquer de Motes, C, Unterholzner, L, Sumner, RP, Ferguson, BJ, Ren, H, Strnadova, P, Bowie, AG & Smith, GL 2013, 'Poxvirus targeting of E3 ligase β-TrCP by molecular mimicry: a mechanism to inhibit NF-κB activation and promote immune evasion and virulence', PLoS Pathogens, vol. 9, no. 2, e1003183. https://doi.org/10.1371/journal.ppat.1003183

APA

Mansur, D. S., Maluquer de Motes, C., Unterholzner, L., Sumner, R. P., Ferguson, B. J., Ren, H., Strnadova, P., Bowie, A. G., & Smith, G. L. (2013). Poxvirus targeting of E3 ligase β-TrCP by molecular mimicry: a mechanism to inhibit NF-κB activation and promote immune evasion and virulence. PLoS Pathogens, 9(2), Article e1003183. https://doi.org/10.1371/journal.ppat.1003183

Vancouver

Mansur DS, Maluquer de Motes C, Unterholzner L, Sumner RP, Ferguson BJ, Ren H et al. Poxvirus targeting of E3 ligase β-TrCP by molecular mimicry: a mechanism to inhibit NF-κB activation and promote immune evasion and virulence. PLoS Pathogens. 2013 Feb;9(2):e1003183. doi: 10.1371/journal.ppat.1003183

Author

Mansur, Daniel S. ; Maluquer de Motes, Carlos ; Unterholzner, Leonie et al. / Poxvirus targeting of E3 ligase β-TrCP by molecular mimicry : a mechanism to inhibit NF-κB activation and promote immune evasion and virulence. In: PLoS Pathogens. 2013 ; Vol. 9, No. 2.

Bibtex

@article{962e2bfc6d3548e1b2c56ab36dbed197,
title = "Poxvirus targeting of E3 ligase β-TrCP by molecular mimicry: a mechanism to inhibit NF-κB activation and promote immune evasion and virulence",
abstract = "The transcription factor NF-κB is essential for immune responses against pathogens and its activation requires the phosphorylation, ubiquitination and proteasomal degradation of IκBα. Here we describe an inhibitor of NF-κB from vaccinia virus that has a closely related counterpart in variola virus, the cause of smallpox, and mechanistic similarity with the HIV protein Vpu. Protein A49 blocks NF-κB activation by molecular mimicry and contains a motif conserved in IκBα which, in IκBα, is phosphorylated by IKKβ causing ubiquitination and degradation. Like IκBα, A49 binds the E3 ligase β-TrCP, thereby preventing ubiquitination and degradation of IκBα. Consequently, A49 stabilised phosphorylated IκBα (p-IκBα) and its interaction with p65, so preventing p65 nuclear translocation. Serine-to-alanine mutagenesis within the IκBα-like motif of A49 abolished β-TrCP binding, stabilisation of p-IκBα and inhibition of NF-κB activation. Remarkably, despite encoding nine other inhibitors of NF-κB, a VACV lacking A49 showed reduced virulence in vivo.",
keywords = "Animals, Cell Line, I-kappa B Kinase, Immune Evasion, Mice, Mice, Inbred BALB C, Molecular Mimicry, Mutagenesis, Site-Directed, NF-kappa B, Phosphorylation, Protein Binding, Ubiquitin-Protein Ligases, Vaccinia virus, Variola virus, Virulence, beta-Transducin Repeat-Containing Proteins",
author = "Mansur, {Daniel S.} and {Maluquer de Motes}, Carlos and Leonie Unterholzner and Sumner, {Rebecca P.} and Ferguson, {Brian J.} and Hongwei Ren and Pavla Strnadova and Bowie, {Andrew G.} and Smith, {Geoffrey L.}",
year = "2013",
month = feb,
doi = "10.1371/journal.ppat.1003183",
language = "English",
volume = "9",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "2",

}

RIS

TY - JOUR

T1 - Poxvirus targeting of E3 ligase β-TrCP by molecular mimicry

T2 - a mechanism to inhibit NF-κB activation and promote immune evasion and virulence

AU - Mansur, Daniel S.

AU - Maluquer de Motes, Carlos

AU - Unterholzner, Leonie

AU - Sumner, Rebecca P.

AU - Ferguson, Brian J.

AU - Ren, Hongwei

AU - Strnadova, Pavla

AU - Bowie, Andrew G.

AU - Smith, Geoffrey L.

PY - 2013/2

Y1 - 2013/2

N2 - The transcription factor NF-κB is essential for immune responses against pathogens and its activation requires the phosphorylation, ubiquitination and proteasomal degradation of IκBα. Here we describe an inhibitor of NF-κB from vaccinia virus that has a closely related counterpart in variola virus, the cause of smallpox, and mechanistic similarity with the HIV protein Vpu. Protein A49 blocks NF-κB activation by molecular mimicry and contains a motif conserved in IκBα which, in IκBα, is phosphorylated by IKKβ causing ubiquitination and degradation. Like IκBα, A49 binds the E3 ligase β-TrCP, thereby preventing ubiquitination and degradation of IκBα. Consequently, A49 stabilised phosphorylated IκBα (p-IκBα) and its interaction with p65, so preventing p65 nuclear translocation. Serine-to-alanine mutagenesis within the IκBα-like motif of A49 abolished β-TrCP binding, stabilisation of p-IκBα and inhibition of NF-κB activation. Remarkably, despite encoding nine other inhibitors of NF-κB, a VACV lacking A49 showed reduced virulence in vivo.

AB - The transcription factor NF-κB is essential for immune responses against pathogens and its activation requires the phosphorylation, ubiquitination and proteasomal degradation of IκBα. Here we describe an inhibitor of NF-κB from vaccinia virus that has a closely related counterpart in variola virus, the cause of smallpox, and mechanistic similarity with the HIV protein Vpu. Protein A49 blocks NF-κB activation by molecular mimicry and contains a motif conserved in IκBα which, in IκBα, is phosphorylated by IKKβ causing ubiquitination and degradation. Like IκBα, A49 binds the E3 ligase β-TrCP, thereby preventing ubiquitination and degradation of IκBα. Consequently, A49 stabilised phosphorylated IκBα (p-IκBα) and its interaction with p65, so preventing p65 nuclear translocation. Serine-to-alanine mutagenesis within the IκBα-like motif of A49 abolished β-TrCP binding, stabilisation of p-IκBα and inhibition of NF-κB activation. Remarkably, despite encoding nine other inhibitors of NF-κB, a VACV lacking A49 showed reduced virulence in vivo.

KW - Animals

KW - Cell Line

KW - I-kappa B Kinase

KW - Immune Evasion

KW - Mice

KW - Mice, Inbred BALB C

KW - Molecular Mimicry

KW - Mutagenesis, Site-Directed

KW - NF-kappa B

KW - Phosphorylation

KW - Protein Binding

KW - Ubiquitin-Protein Ligases

KW - Vaccinia virus

KW - Variola virus

KW - Virulence

KW - beta-Transducin Repeat-Containing Proteins

U2 - 10.1371/journal.ppat.1003183

DO - 10.1371/journal.ppat.1003183

M3 - Journal article

C2 - 23468625

VL - 9

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 2

M1 - e1003183

ER -