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在非人类灵长类动物中,基孔肯雅热病涉及巨噬细胞中的长期病毒持续存在。

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

机构信息

CEA, Division of Immuno-Virology/Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses, France.

出版信息

J Clin Invest. 2010 Mar;120(3):894-906. doi: 10.1172/JCI40104. Epub 2010 Feb 22.

DOI:10.1172/JCI40104
PMID:20179353
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2827953/
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.

摘要

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。

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J Clin Invest. 2010 Mar;120(3):894-906. doi: 10.1172/JCI40104. Epub 2010 Feb 22.
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本文引用的文献

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Chikungunya virus takes centre stage in virally induced arthritis: possible cellular and molecular mechanisms to pathogenesis.基孔肯雅病毒在病毒诱导性关节炎中的核心地位:发病机制的可能细胞和分子机制。
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IL-1beta, IL-6, and RANTES as biomarkers of Chikungunya severity.白细胞介素-1β、白细胞介素-6和调节激活正常T细胞表达和分泌因子作为基孔肯雅热严重程度的生物标志物。
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Primary infection with simian immunodeficiency virus: plasmacytoid dendritic cell homing to lymph nodes, type I interferon, and immune suppression.猿猴免疫缺陷病毒的原发性感染:浆细胞样树突状细胞归巢至淋巴结、I型干扰素与免疫抑制
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Atypical Chikungunya virus infections: clinical manifestations, mortality and risk factors for severe disease during the 2005-2006 outbreak on Réunion.非典型基孔肯雅病毒感染:2005 - 2006年留尼汪岛疫情期间的临床表现、死亡率及重症疾病风险因素
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Estimating Chikungunya prevalence in La Réunion Island outbreak by serosurveys: two methods for two critical times of the epidemic.通过血清学调查估计留尼汪岛基孔肯雅热疫情的流行率:针对疫情两个关键时期的两种方法
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