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Cytokine patterns in a comparative model of arenavirus haemorrhagic fever in guinea pigs.
- Source :
-
The Journal of general virology [J Gen Virol] 2008 Oct; Vol. 89 (Pt 10), pp. 2569-2579. - Publication Year :
- 2008
-
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-gamma) 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-alpha), 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-alpha, IFN-gamma, 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.
- Subjects :
- Animals
Arenaviridae Infections virology
Cytokines genetics
Disease Models, Animal
Guinea Pigs
Hemorrhagic Fevers, Viral virology
Humans
Immunity, Innate immunology
Inflammation immunology
Pichinde virus immunology
RNA, Messenger genetics
RNA, Messenger metabolism
Severity of Illness Index
Virulence
Arenaviridae Infections immunology
Arenaviridae Infections physiopathology
Cytokines metabolism
Hemorrhagic Fevers, Viral immunology
Pichinde virus pathogenicity
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1317
- Volume :
- 89
- Issue :
- Pt 10
- Database :
- MEDLINE
- Journal :
- The Journal of general virology
- Publication Type :
- Academic Journal
- Accession number :
- 18796726
- Full Text :
- https://doi.org/10.1099/vir.0.2008/002048-0