Characterization of a MAVS Ortholog From the Chinese Tree Shrew (Tupaia Belangeri Chinensis)

Dev Comp Immunol. 2015 Sep;52(1):58-68. doi: 10.1016/j.dci.2015.04.014. Epub 2015 Apr 27.

Abstract

Human mitochondrial antiviral signaling protein (hMAVS, also known as IPS-1, VISA, or Cardif) is essential for antiviral innate immunity. The Chinese tree shrew (Tupaia belangeri chinenses), a close relative of primates, is emerging as a potential animal model for investigating viral infection. However, there is a lack of biological knowledge about the antiviral innate immunity of the tree shrew. In this study, we identified and characterized the function of the Chinese tree shrew MAVS gene (tMAVS). The cDNA of tMAVS was 2771 bp in length and encoded a polypeptide of 501 amino acids. Phylogenetic analyses based on the amino acid sequences revealed a closer affinity of tMAVS with those of primates. Quantitative real-time PCR analysis indicated that tMAVS mRNA was constitutively expressed in all seven tissues analyzed in this study. The tMAVS mRNA expression was rapidly and significantly increased after RNA virus infections. Ectopic-expression of tMAVS significantly potentiated the virus-triggered activation of IRF3, NF-κB and interferon-β (IFN-β), whereas knockdown of tMAVS displayed the opposite effect. Furthermore, tMAVS mutants lacking the caspase activation and recruitment (CARD) domains or the transmembrane (TM) domain were unable to induce IFN-β. Similar with hMAVS, mitochondrial localization of tMAVS was dependent on its domain. Collectively, this study revealed evolutionary conservation of the MAVS antiviral signaling pathway in the Chinese tree shrew.

Keywords: Antiviral innate immunity; Evolutionary conservation; MAVS; Tree shrew.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Base Sequence
  • Disease Models, Animal
  • Evolution, Molecular
  • Humans
  • Immunity, Innate / genetics
  • Interferon Regulatory Factor-3 / genetics
  • Interferon Regulatory Factor-3 / metabolism
  • Interferon-beta / genetics
  • Interferon-beta / metabolism
  • Molecular Sequence Data
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Phylogeny
  • Protein Engineering
  • Protein Structure, Tertiary / genetics
  • Signal Transduction / genetics
  • Tupaiidae / genetics
  • Tupaiidae / immunology*
  • Virus Diseases / genetics
  • Virus Diseases / immunology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Interferon Regulatory Factor-3
  • NF-kappa B
  • VISA protein, human
  • Interferon-beta