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 G. Wood, Xiaoyong Bao

Research output: Contribution to journalArticle

12 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Virology

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    Chen, Y., Deng, X., Deng, J., Zhou, J., Ren, Y., Liu, S., Prusak, D. J., Wood, T. G., & Bao, X. (2016). Functional motifs responsible for human metapneumovirus M2-2-mediated innate immune evasion. Virology, 499, 361-368. https://doi.org/10.1016/j.virol.2016.09.026