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 7

Immunohistochemical findings in spleen (A–I) and liver (J–L) collected from CHIKV-infected macaques at various times.

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Immunohistochemical findings in spleen (A–I) and liver (J–L) collected f...
(A) Viral antigens were detected by immunohistochemistry at 6 dpi in the cytoplasm of numerous mononuclear cells (brown staining) of the splenic red pulp. Staining was associated with pronounced macrophage infiltration (see Figure 4). Macrophage sheathed capillaries of the red pulp are denoted by arrows. (B) Viral antigen detected in mononuclear cells of the enlarged follicles of the splenic white pulp at 44 dpi. (C) Isotypic control assay (top) and control assay using splenic tissue of an uninfected macaque (bottom). (D–L) CHIKV antigen-positive cells are indicated (arrowhead). (D and E) CHIKV antigen in CD68+ macrophages of the spleen, 44 dpi. (G and H) CHIKV antigen in S100+ splenic dendritic cells, 6 dpi. (J and K) CHIKV antigen in FVIII+ endothelial cells lining the sinusoids of the liver, 44 dpi. (D, G, and J) CHIKV antigen labeling is shown in red; nuclei are stained in blue. (E, H, K) Merged images, with cell-specific markers in green. (F, I, and L) Isotype control assays. Scale bars: 200 μm (A–C); 20 μm (D–L).