The alternatively spliced porcine FcγRI regulated PRRSV-ADE infection and proinflammatory cytokine production

Dev Comp Immunol. 2019 Jan:90:186-198. doi: 10.1016/j.dci.2018.09.019. Epub 2018 Sep 28.

Abstract

Receptors for the Fc region of IgG (FcγRs) play a key role in protecting the immune system and host from infection. In this study, we described the cloning, sequencing and characterization of porcine FcγRI, and reported six different FcγRI isoforms, four of which have never been reported before. Further analysis revealed that FcγR isoforms are generated by alternative splicing mechanisms, including two membrane isoforms and four soluble isoforms. Importantly, we found FcγRI splice variants differentially influence PRRSV antibody-dependent enhancement (ADE) effects. Membrane pCD64-T1 promotes endocytosis of the PRRSV-antibody complex to enhance PRRSV replication, and soluble pCD64-T3 has no ADE effect on PRRSV proliferation, but shows an inflammation enhancement effect. The differential expression of selective splicing in primary PAM cells and 3D4/21 cell lines are altered and regulated by PRRSV infection and inflammatory environment. Our results indicated that porcine FcγRI plays dual regulatory roles in PRRSV multiplication and PRRSV inflammation process by the alternatively spliced mechanism, which will be a new target in PRRSV prevention and control.

Keywords: ADE; Alternative splicing; FcγRI; Inflammation; PRRSV; Porcine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • Antibodies, Viral / metabolism*
  • Antibody-Dependent Enhancement
  • Cell Line
  • Cloning, Molecular
  • Cytokines / metabolism
  • Inflammation / immunology*
  • Inflammation Mediators / metabolism
  • Macrophages, Alveolar / immunology*
  • Macrophages, Alveolar / virology
  • Porcine Reproductive and Respiratory Syndrome / immunology*
  • Porcine respiratory and reproductive syndrome virus / physiology*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA Splicing
  • Receptors, IgG / genetics*
  • Receptors, IgG / metabolism*
  • Swine / immunology*
  • Virus Replication

Substances

  • Antibodies, Viral
  • Cytokines
  • Inflammation Mediators
  • Protein Isoforms
  • Receptors, IgG