小柯机器人

法国巴黎大学Ali Amara和Laurent Meertens等研究人员合作发现，FHL1是基孔肯雅病毒（CHIKV）感染的主要宿主因子。这一研究成果2019年9月25日在线发表于国际学术期刊《自然》。

研究人员确定了四个半LIM域蛋白1（FHL1）作为CHIKV在人类和小鼠中存在和发病机理所必需的宿主因子。FHL1表达的敲除可抑制几种CHIKV株和o'nyong-nyong病毒的感染，但不会抑制其他α病毒和黄病毒的感染。相反，FHL1的表达会在通常不表达它的细胞中促进CHIKV感染。FHL1与CHIKV的nsP3蛋白的高变域直接相互作用，对于病毒RNA的复制至关重要。FHL1在CHIKV靶细胞中高表达，在肌肉中尤其丰富。来自缺乏功能性FHL1的Emery–Dreifuss肌营养不良患者的皮肤成纤维细胞和肌细胞对CHIKV感染具有抵抗力。此外，在Fhl1基因敲除小鼠中检测不到CHIKV感染。

总的来说，这项研究表明FHL1是由宿主表达的关键因子，它能引起CHIKV感染，并确定nsP3和FHL1之间的相互作用是开发抗CHIKV疗法的有望靶标。

据介绍，CHIKV是一种重新出现的甲型病毒，通过蚊虫叮咬传播给人类，并引起肌肉骨骼和关节疼痛。尽管进行了深入的研究，但对于CHIKV感染至关重要的人类细胞因子仍然未知，这妨碍了对病毒发病机理和抗CHIKV治疗方法的理解。

附：英文原文

Title: FHL1 is a major host factor for chikungunya virus infection

Author: Laurent Meertens, Mohamed Lamine Hafirassou, Thrse Couderc, Lucie Bonnet-Madin, Vasiliya Kril, Beate M. Kmmerer, Athena Labeau, Alexis Brugier, Etienne Simon-Loriere, Julien Burlaud-Gaillard, Ccile Doyen, Laura Pezzi, Thibaud Goupil, Sophia Rafasse, Pierre-Olivier Vidalain, Anne Bertrand-Legout, Lucie Gueneau, Raul Juntas-Morales, Rabah Ben Yaou, Gisle Bonne, Xavier de Lamballerie, Monsef Benkirane, Philippe Roingeard, Constance Delaugerre, Marc Lecuit, Ali Amara

Issue&Volume: 2019-09-25

Abstract: 

Chikungunya virus (CHIKV) is a re-emerging alphavirus that is transmitted to humans by mosquito bites and causes musculoskeletal and joint pain1,2. Despite intensive investigations, the human cellular factors that are critical for CHIKV infection remain unknown, hampering the understanding of viral pathogenesis and the development of anti-CHIKV therapies. Here we identified the four-and-a-half LIM domain protein 1 (FHL1)3 as a host factor that is required for CHIKV permissiveness and pathogenesis in humans and mice. Ablation of FHL1 expression results in the inhibition of infection by several CHIKV strains and o’nyong-nyong virus, but not by other alphaviruses and flaviviruses. Conversely, expression of FHL1 promotes CHIKV infection in cells that do not normally express it. FHL1 interacts directly with the hypervariable domain of the nsP3 protein of CHIKV and is essential for the replication of viral RNA. FHL1 is highly expressed in CHIKV-target cells and is particularly abundant in muscles3,4. Dermal fibroblasts and muscle cells derived from patients with Emery–Dreifuss muscular dystrophy that lack functional FHL15 are resistant to CHIKV infection. Furthermore,  CHIKV infection  is undetectable in Fhl1-knockout mice. Overall, this study shows that FHL1 is a key factor expressed by the host that enables CHIKV infection and identifies the interaction between nsP3 and FHL1 as a promising target for the development of anti-CHIKV therapies.

DOI: 10.1038/s41586-019-1578-4

Source: https://www.nature.com/articles/s41586-019-1578-4

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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