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 5

CHIKV distribution in organs of CHIKV-infected macaques, 2–97 dpi.

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CHIKV distribution in organs of CHIKV-infected macaques, 2–97 dpi. (A) R...
(A) Relative quantitative RT-PCR in spleen, lymph nodes, liver, joint, and muscle of macaques inoculated with 103 PFU (white symbols), 106 PFU (gray symbols), or more than 107 PFU (black symbols). The CHIKV RNA copy number was normalized to GAPDH copy number. CHIKV RNA was also quantified in CSF. For each sample, the relative copy number represents the mean of at least 3 independent RT-PCR amplifications carried out on 2 independent RNA extractions. Vertical error bar denotes SEM. NT, not tested; ND, not detected. (B–J) In situ hybridization assays in spleen (B–D), muscle (E–G), and joint tissue (H–J) of macaques infected with 103 PFU, 6 dpi. (B, E, and H) CHIKV 26S RNA was detected in the cytoplasm of many mononuclear cells surrounding follicular centers (asterisks) of the splenic white pulp (B), and in some endothelial cells (arrowheads) surrounding vascular lumen (asterisk) of the muscular endomysial tissue (E). (H) Some vRNA was also detected in the cytoplasm of a few cells in the synovial tissue (arrowheads). (C, F, and I) Control assay using probe specific for RRV 26S RNA. (D, G, and J) Control assay using CHIKV 26S RNA on tissues of an uninfected macaque. Scale bars: 200 μm (B–D); 20 μm (E–J).