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Infection of peripheral blood mononuclear cells with neuropathogenic equine herpesvirus type-1 strain Ab4 reveals intact interferon-α induction and induces suppression of anti-inflammatory interleukin-10 responses in comparison to other viral strains.

Abstract
The recent increase in incidence, morbidity, and mortality of neurological disease induced by equine herpesvirus type 1 (EHV-1) has suggested a change of virulence of the virus. The exact mechanisms by which EHV-1 induces neurologic disease are not known. Environmental, viral, and host risk factors might contribute to neurological manifestation. Here, we investigated innate interferon-α (IFN-α), interleukin-10 (IL-10) and IL-4 responses after infection of equine peripheral blood mononuclear cells (PBMC) with EHV-1 using an available cytokine multiplex assay. Three viral strains representing an older isolate (RacL11), a recent abortigenic (NY03) and a neuropathogenic isolate (Ab4) were compared to identify differences in cytokine induction that might explain the increased pathogenicity of Ab4. Cytokine concentrations were also compared between foals, mares after birth, pregnant and non-pregnant mares to investigate whether immune responses to EHV-1 infection are influenced by age or pregnancy status. PBMC from all groups secreted high concentrations of anti-viral IFN-α in response to EHV-1. A reduced response was observed in foals compared to non-pregnant mares. EHV-1 infection induced moderate IL-10 and overall low IL-4 secretion. Ab4 infection resulted in a significant reduction of IL-10 responses in adult horses. IL-10 and IL-4 responses were lower in foals than in most mare groups. These data suggested that EHV-1 induces robust IFN-α secretion without major differences between viral strains. However, anti-inflammatory IL-10 production was significantly reduced after infection with neuropathogenic Ab4. The ability of this EHV-1 isolate to down-regulate IL-10 production might contribute to increased local inflammation and a higher risk for neurological manifestation of the disease after infection with Ab4.
AuthorsBettina Wagner, Christine Wimer, Heather Freer, Nikolaus Osterrieder, Hollis N Erb
JournalVeterinary immunology and immunopathology (Vet Immunol Immunopathol) Vol. 143 Issue 1-2 Pg. 116-24 (Sep 15 2011) ISSN: 1873-2534 [Electronic] Netherlands
PMID21764140 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier B.V. All rights reserved.
Chemical References
  • Interferon-alpha
  • Interleukin-10
  • Interleukin-4
Topics
  • Animals
  • Animals, Newborn
  • Female
  • Herpesviridae Infections (immunology, veterinary, virology)
  • Herpesvirus 1, Equid (classification, immunology, pathogenicity)
  • Horse Diseases (immunology, virology)
  • Horses (immunology, virology)
  • Immune Tolerance
  • Interferon-alpha (biosynthesis)
  • Interleukin-10 (biosynthesis)
  • Interleukin-4 (biosynthesis)
  • Leukocytes, Mononuclear (immunology, virology)
  • Pregnancy
  • Pregnancy Complications, Infectious (immunology, veterinary, virology)
  • Species Specificity

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