Engagement of soluble resistance-related calcium binding protein (sorcin) with foot-and-mouth disease virus (FMDV) VP1 inhibits type I interferon response in cells

Vet Microbiol. 2013 Sep 27;166(1-2):35-46. doi: 10.1016/j.vetmic.2013.04.028. Epub 2013 May 21.

Abstract

Foot-and-mouth disease (FMD) is an acute, highly contagious animal disease caused by FMD virus (FMDV). Although FMDV-induced immunosuppression in host has been well established, the exact molecular mechanism for such induction is not very clear. We report here the identification of FMDV VP1 as an interferon-suppressor by interacting with soluble resistance-related calcium binding protein (sorcin). We found that VP1 suppressed tumor necrosis factor (TNF)-α or Sendai virus (SeV)-induced type I interferon response in HEK293T cells, and that this suppression could be completely abolished by knockdown of sorcin by shRNA. Furthermore, overexpression of sorcin inhibited type I interferon response. Conversely, TNF- or SeV-induced type I interferon response increased when sorcin knocked down, leading to inhibition of vesicular stomatitis virus (VSV) replication. Thus, VP1-induced suppression of type I interferon is mediated by interacting with sorcin, a protein that appears to regulate cell response to viral infections.

Keywords: FMDV; FMDV VP1; Immunosuppression; Interferon; SeV; Sendai virus; Sorcin; foot-and-mouth disease virus; soluble resistance-related calcium binding protein; sorcin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Capsid Proteins / genetics
  • Capsid Proteins / metabolism*
  • Foot-and-Mouth Disease / genetics
  • Foot-and-Mouth Disease / immunology
  • Foot-and-Mouth Disease / metabolism*
  • Foot-and-Mouth Disease / virology
  • Foot-and-Mouth Disease Virus / genetics
  • Foot-and-Mouth Disease Virus / metabolism*
  • Humans
  • Interferon Type I / biosynthesis*
  • Protein Binding
  • RNA, Small Interfering / genetics
  • Swine
  • Swine Diseases / genetics
  • Swine Diseases / immunology
  • Swine Diseases / metabolism*
  • Swine Diseases / virology

Substances

  • Calcium-Binding Proteins
  • Capsid Proteins
  • Interferon Type I
  • RNA, Small Interfering
  • SRI protein, human
  • VP1 protein, Foot-and-mouth disease virus