Cytokine patterns in a comparative model of arenavirus haemorrhagic fever in guinea pigs

Erin P. Scott, Judith Aronson

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Arenaviruses such as Lassa virus cause a spectrum of disease in humans ranging from mild febrile illness to lethal haemorrhagic fever. The contributions of innate immunity to protection or pathogenicity are unknown. We compared patterns of expression of cytokines of innate immunity in mild versus severe arenavirus disease using an established guinea pig model based on the macrophage-tropic arenavirus Pichinde virus (PICV). Cytokine transcripts were measured by using real-time RT-PCR in target organs and blood during mild infection (caused by PICV, P2 variant) and lethal haemorrhagic fever (caused by PICV, P18 variant). In the initial peritoneal target cells, virulent P18 infection was associated with significantly increased gamma interferon (IFN-γ) and monocyte chemoattractant protein-1 (MCP-1, CCL2) mRNA levels relative to P2 infection. Peritoneal cells from P18-infected animals had decreased tumour necrosis factor alpha (TNF-α), interleukin (IL)-8 (CXCL-8) and IL-12p40 transcripts relative to mock-infected animals. Late in infection, P18-infected peripheral blood leukocytes (PBL) had decreased TNF-α, IFN-γ, and regulated upon activation, normal T cell expressed and secreted (RANTES, CCL-5) cytokine transcripts relative to P2-infected PBL. We conclude that, in severe arenavirus disease, patterns of cytokine expression in the initially infected cells favour recruitment of additional target monocytes, while inhibiting some of their pro-inflammatory responses. Suppression rather than overexpression of pro-inflammatory cytokines accompanied the terminal shock in this model of arenavirus haemorrhagic fever.

Original languageEnglish (US)
Pages (from-to)2569-2579
Number of pages11
JournalJournal of General Virology
Volume89
Issue number10
DOIs
StatePublished - 2008

Fingerprint

Arenavirus
Pichinde virus
Guinea Pigs
Fever
Cytokines
Infection
Interleukin-8
Innate Immunity
Leukocytes
Lassa virus
Tumor Necrosis Factor-alpha
Chemokine CCL5
Chemokine CCL2
Interferon-alpha
Interferon-gamma
Virulence
Real-Time Polymerase Chain Reaction
Monocytes
Shock
Macrophages

ASJC Scopus subject areas

  • Virology

Cite this

Cytokine patterns in a comparative model of arenavirus haemorrhagic fever in guinea pigs. / Scott, Erin P.; Aronson, Judith.

In: Journal of General Virology, Vol. 89, No. 10, 2008, p. 2569-2579.

Research output: Contribution to journalArticle

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