CEA, Division of Immuno-Virology/Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses, France.
J Clin Invest. 2010 Mar;120(3):894-906. doi: 10.1172/JCI40104. Epub 2010 Feb 22.
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.
基孔肯雅热病毒(CHIKV)是一种通过蚊子传播的甲病毒,可引起人类发热、皮疹和肌肉及关节疼痛。最近印度洋岛屿和印度的 CHIKV 再次出现或重新出现,这凸显了更好地了解该疾病发病机制的必要性。以前的 CHIKV 疾病模型使用年轻或免疫功能低下的小鼠,但这些模型不能重现人类疾病模式,不适合测试基于免疫的治疗方法。在此,我们描述了我们认为是一种新型成年、免疫功能正常的食蟹猴 CHIKV 感染模型。这些动物的 CHIKV 感染重现了人类疾病中观察到的病毒、临床和病理特征。在这些猕猴中,在关节、肌肉、淋巴器官和肝脏中观察到长期的 CHIKV 感染,这可以解释人类中观察到的 CHIKV 疾病症状持续时间长的原因。此外,该研究还确定了巨噬细胞是体内 CHIKV 感染后期的主要细胞储库。这种 CHIKV 病理生理学模型应能开发新的治疗和/或预防策略。