Activation of p38 MAPK by feline infectious peritonitis virus regulates pro-inflammatory cytokine production in primary blood-derived feline mononuclear cells

Virology. 2009 Feb 5;384(1):135-43. doi: 10.1016/j.virol.2008.11.006. Epub 2008 Dec 5.

Abstract

Feline infectious peritonitis (FIP) is an invariably fatal disease of cats caused by systemic infection with a feline coronavirus (FCoV) termed feline infectious peritonitis virus (FIPV). The lethal pathology associated with FIP (granulomatous inflammation and T-cell lymphopenia) is thought to be mediated by aberrant modulation of the immune system due to infection of cells such as monocytes and macrophages. Overproduction of pro-inflammatory cytokines occurs in cats with FIP, and has been suggested to play a significant role in the disease process. However, the mechanism underlying this process remains unknown. Here we show that infection of primary blood-derived feline mononuclear cells by FIPV WSU 79-1146 and FIPV-DF2 leads to rapid activation of the p38 MAPK pathway and that this activation regulates production of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). FIPV-induced p38 MAPK activation and pro-inflammatory cytokine production was inhibited by the pyridinyl imidazole inhibitors SB 203580 and SC 409 in a dose-dependent manner. FIPV-induced p38 MAPK activation was observed in primary feline blood-derived mononuclear cells individually purified from multiple SPF cats, as was the inhibition of TNF-alpha production by pyridinyl imidazole inhibitors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cats
  • Cell Nucleus / enzymology
  • Cytokines / biosynthesis*
  • Enzyme Activation
  • Feline Infectious Peritonitis / virology*
  • Feline Panleukopenia Virus / pathogenicity*
  • Feline Panleukopenia Virus / physiology
  • Inflammation / virology
  • Leukocytes, Mononuclear / enzymology
  • Leukocytes, Mononuclear / virology
  • Virus Replication
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Cytokines
  • p38 Mitogen-Activated Protein Kinases