Chikungunya disease in nonhuman primates involves long-term viral persistence in macrophages
Karine Labadie, … , Roger Le Grand, Pierre Roques
Karine Labadie, … , Roger Le Grand, Pierre Roques
Published February 22, 2010
Citation Information: J Clin Invest. 2010;120(3):894-906. https://doi.org/10.1172/JCI40104.
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Research Article

Chikungunya disease in nonhuman primates involves long-term viral persistence in macrophages

Abstract

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that induces in humans a disease characterized by fever, rash, and pain in muscles and joints. The recent emergence or reemergence of CHIKV in the Indian Ocean Islands and India has stressed the need to better understand the pathogenesis of this disease. Previous CHIKV disease models have used young or immunodeficient mice, but these do not recapitulate human disease patterns and are unsuitable for testing immune-based therapies. Herein, we describe what we believe to be a new model for CHIKV infection in adult, immunocompetent cynomolgus macaques. CHIKV infection in these animals recapitulated the viral, clinical, and pathological features observed in human disease. In the macaques, long-term CHIKV infection was observed in joints, muscles, lymphoid organs, and liver, which could explain the long-lasting CHIKV disease symptoms observed in humans. In addition, the study identified macrophages as the main cellular reservoirs during the late stages of CHIKV infection in vivo. This model of CHIKV physiopathology should allow the development of new therapeutic and/or prophylactic strategies.

Authors

Karine Labadie, Thibaut Larcher, Christophe Joubert, Abdelkrim Mannioui, Benoit Delache, Patricia Brochard, Lydie Guigand, Laurence Dubreil, Pierre Lebon, Bernard Verrier, Xavier de Lamballerie, Andreas Suhrbier, Yan Cherel, Roger Le Grand, Pierre Roques

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Figure 3

Mononuclear cell infiltration in tissues of macaques inoculated with high-dose CHIKV.

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Mononuclear cell infiltration in tissues of macaques inoculated with hig...
(A and B) Tissues lesions in ankle joint collected from a 7-dpi macaque inoculated with 108 PFU CHIKV. Mild fibrinous exudate (arrows) was associated with mononuclear cell infiltration of the synovial tissue (arrowheads). Hematoxylin eosin safran staining. Scale bars: 300 μm (A); 100 μm (B). (C) Staining of cerebrospinal fluid cells collected from a macaque inoculated with 108 PFU showing clinical signs of meningoencephalitis. Infiltrating cells were mainly CD8+ T cells and activated monocyte/macrophages (CD14+CD16+HLA-DR+). Numbers denote percent of population in the respective gate or quadrant.