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

被引:417
作者
Labadie, Karine [2 ]
Larcher, Thibaut [3 ]
Joubert, Christophe [2 ]
Mannioui, Abdekrim [2 ]
Delache, Benoit [2 ]
Brochard, Patricia [2 ]
Guigand, Lydie [3 ]
Dubreil, Laurence [3 ]
Lebon, Pierre [4 ]
Verrier, Bernard [5 ]
de lamballerie, Xavier [6 ,7 ]
Suhrbier, Andreas [8 ]
Cherel, Yan [3 ]
Le Grand, Roger [2 ]
Roques, Pierre [1 ,2 ]
机构
[1] CEA, Inst Emerging Dis & Innovat Therapies, Serv Immunovirol, Div Immunovirol,DSV iMETI, F-92265 Fontenay Aux Roses, France
[2] Paris Sud 11, UMR E1, Orsay, France
[3] Ecole Natl Vet, INRA, UMR 703, Nantes, France
[4] Univ Paris 05, Hop Cochin St Vincent de Paul, Serv Virol, Paris, France
[5] IBCP IFR 128, UMR 5086, CNRS, Lyon, France
[6] Univ Mediterranee, Unite Virus Emergents, Marseille, France
[7] Inst Rech Dev, Marseille, France
[8] Queensland Inst Med Res, Australian Ctr Int & Trop Hlth, Brisbane, Qld 4006, Australia
关键词
ROSS-RIVER-VIRUS; REUNION ISLAND; I INTERFERON; MACACA-FASCICULARIS; REPLICON VECTOR; DENDRITIC CELLS; MOUSE MODEL; INFECTION; PATHOLOGY; EPIDEMIC;
D O I
10.1172/JCI40104
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:894 / 906
页数:13
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