Functional motifs responsible for human metapneumovirus M2-2-mediated innate immune evasion

Yu Chen, Xiaoling Deng, Junfang Deng, Jiehua Zhou, Yuping Ren, Shengxuan Liu, Deborah J. Prusak, Thomas Wood, Xiaoyong Bao

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Human metapneumovirus (hMPV) is a major cause of lower respiratory infection in young children. Repeated infections occur throughout life, but its immune evasion mechanisms are largely unknown. We recently found that hMPV M2-2 protein elicits immune evasion by targeting mitochondrial antiviral-signaling protein (MAVS), an antiviral signaling molecule. However, the molecular mechanisms underlying such inhibition are not known. Our mutagenesis studies revealed that PDZ-binding motifs, 29-DEMI-32 and 39-KEALSDGI-46, located in an immune inhibitory region of M2-2, are responsible for M2-2-mediated immune evasion. We also found both motifs prevent TRAF5 and TRAF6, the MAVS downstream adaptors, to be recruited to MAVS, while the motif 39-KEALSDGI-46 also blocks TRAF3 migrating to MAVS. In parallel, these TRAFs are important in activating transcription factors NF-kB and/or IRF-3 by hMPV. Our findings collectively demonstrate that M2-2 uses its PDZ motifs to launch the hMPV immune evasion through blocking the interaction of MAVS and its downstream TRAFs.

Original languageEnglish (US)
Pages (from-to)361-368
Number of pages8
JournalVirology
Volume499
DOIs
StatePublished - Dec 1 2016

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Metapneumovirus
Immune Evasion
Antiviral Agents
Proteins
TNF Receptor-Associated Factor 5
TNF Receptor-Associated Factor 3
TNF Receptor-Associated Factor 6
Activating Transcription Factors
Amino Acid Motifs
NF-kappa B
Mutagenesis
Respiratory Tract Infections
Infection

Keywords

  • hMPV
  • Innate immune response
  • M2-2 motif
  • MAVS
  • TRAF

ASJC Scopus subject areas

  • Virology

Cite this

Functional motifs responsible for human metapneumovirus M2-2-mediated innate immune evasion. / Chen, Yu; Deng, Xiaoling; Deng, Junfang; Zhou, Jiehua; Ren, Yuping; Liu, Shengxuan; Prusak, Deborah J.; Wood, Thomas; Bao, Xiaoyong.

In: Virology, Vol. 499, 01.12.2016, p. 361-368.

Research output: Contribution to journalArticle

Chen, Y, Deng, X, Deng, J, Zhou, J, Ren, Y, Liu, S, Prusak, DJ, Wood, T & Bao, X 2016, 'Functional motifs responsible for human metapneumovirus M2-2-mediated innate immune evasion', Virology, vol. 499, pp. 361-368. https://doi.org/10.1016/j.virol.2016.09.026
Chen, Yu ; Deng, Xiaoling ; Deng, Junfang ; Zhou, Jiehua ; Ren, Yuping ; Liu, Shengxuan ; Prusak, Deborah J. ; Wood, Thomas ; Bao, Xiaoyong. / Functional motifs responsible for human metapneumovirus M2-2-mediated innate immune evasion. In: Virology. 2016 ; Vol. 499. pp. 361-368.
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