Unité Epidémiologie et Physiopathologie des Virus Oncogènes-CNRS URA1930, Institut Pasteur, Paris, France.
PLoS One. 2007 Jun 13;2(6):e527. doi: 10.1371/journal.pone.0000527.
Chikungunya (CHIK) virus is a mosquito-transmitted alphavirus that causes in humans an acute infection characterised by fever, polyarthralgia, head-ache, and myalgia. Since 2005, the emergence of CHIK virus was associated with an unprecedented magnitude outbreak of CHIK disease in the Indian Ocean. Clinically, this outbreak was characterized by invalidating poly-arthralgia, with myalgia being reported in 97.7% of cases. Since the cellular targets of CHIK virus in humans are unknown, we studied the pathogenic events and targets of CHIK infection in skeletal muscle.
METHODOLOGY/PRINCIPAL FINDINGS: Immunohistology on muscle biopsies from two CHIK virus-infected patients with myositic syndrome showed that viral antigens were found exclusively inside skeletal muscle progenitor cells (designed as satelllite cells), and not in muscle fibers. To evaluate the ability of CHIK virus to replicate in human satellite cells, we assessed virus infection on primary human muscle cells; viral growth was observed in CHIK virus-infected satellite cells with a cytopathic effect, whereas myotubes were essentially refractory to infection.
CONCLUSIONS/SIGNIFICANCE: This report provides new insights into CHIK virus pathogenesis, since it is the first to identify a cellular target of CHIK virus in humans and to report a selective infection of muscle satellite cells by a viral agent in humans.
基孔肯雅热(CHIK)病毒是一种经蚊子传播的甲病毒,可引起人类急性感染,其特征为发热、多发性关节炎、头痛和肌痛。自 2005 年以来,基孔肯雅热病毒的出现与印度洋地区发生的大规模基孔肯雅热疾病爆发有关。临床上,此次爆发的特点是多发性关节炎无效,97.7%的病例报告有肌痛。由于人类中基孔肯雅热病毒的细胞靶标未知,我们研究了骨骼肌中基孔肯雅热感染的发病事件和靶标。
方法/主要发现:对两名患有肌病综合征的基孔肯雅热病毒感染患者的肌肉活检进行免疫组织化学分析显示,病毒抗原仅存在于骨骼肌祖细胞(称为卫星细胞)内,而不存在于肌纤维中。为了评估 CHIK 病毒在人卫星细胞中的复制能力,我们评估了对原代人肌肉细胞的病毒感染;在具有细胞病变效应的 CHIK 病毒感染的卫星细胞中观察到病毒生长,而肌管基本上对感染具有抗性。
结论/意义:本报告提供了对 CHIK 病毒发病机制的新见解,因为这是首次在人类中确定了 CHIK 病毒的细胞靶标,并报告了一种病毒制剂在人类中选择性感染肌肉卫星细胞。