Open Access Highly Accessed Hypothesis

A new treatment for neurogenic inflammation caused by EV71 with CR2-targeted complement inhibitor

Shaofu Qiu1, Nan Liu1, Leili Jia1, Guang Yang1, Wenli Su1, Jing Li1, Lixue Song2, Chaojie Yang1, Jian Wang1, Chuanfu Zhang1, Zhongqiang Wang1, Fei Qiao3, Stephen Tomlinson3, Carl Atkinson3, Yansong Sun1, Liuyu Huang1, Hongbin Song1*, Yong Wang1* and Zhenjun Li4*

Author Affiliations

1 Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing 100071, China

2 Department of Pharmacology, General Hospital of Beijing Military Region, Beijing 100700, China

3 Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina 29425, USA

4 State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Diseases Prevention and Control, Chinese Center for Disease Control and Prevention, Beijing, 102206, China

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Virology Journal 2012, 9:285  doi:10.1186/1743-422X-9-285

Published: 23 November 2012



Enterovirus 71 (EV71), one of the most important neurotropic EVs, has caused death and long-term neurological sequelae in hundreds of thousands of young children in the Asia-Pacific region in the past decade. The neurological diseases are attributed to infection by EV71 inducing an extensive peripheral and central nervous system (CNS) inflammatory response with abnormal cytokine production and lymphocyte depletion induced by EV71 infection. In the absence of specific antiviral agents or vaccines, an effective immunosuppressive strategy would be valuable to alleviate the severity of the local inflammation induced by EV71 infection.

Presentation of the hypothesis

The complement system plays a pivotal role in the inflammatory response. Inappropriate or excessive activation of the complement system results in a severe inflammatory reaction or numerous pathological injuries. Previous studies have revealed that EV71 infection can induce complement activation and an inflammatory response of the CNS. CR2-targeted complement inhibition has been proved to be a potential therapeutic strategy for many diseases, such as influenza virus-induced lung tissue injury, postischemic cerebral injury and spinal cord injury. In this paper, a mouse model is proposed to test whether a recombinant fusion protein consisting of CR2 and a region of Crry (CR2-Crry) is able to specifically inhibit the local complement activation induced by EV71 infection, and to observe whether this treatment strategy can alleviate or even cure the neurogenic inflammation.

Testing the hypothesis

CR2-Crry is expressed in CHO cells, and its biological activity is determined by complement inhibition assays. 7-day-old ICR mice are inoculated intracranially with EV71 to duplicate the neurological symptoms. The mice are then divided into two groups, in one of which the mice are treated with CR2-Crry targeted complement inhibitor, and in the other with phosphate-buffered saline. A group of mice deficient in complement C3, the breakdown products of which bind to CR2, are also infected with EV71 virus. The potential bioavailability and efficacy of the targeted complement inhibitor are evaluated by histology, immunofluorescence staining and radiolabeling.

Implications of the hypothesis

CR2-Crry-mediated targeting complement inhibition will alleviate the local inflammation and provide an effective treatment for the severe neurological diseases associated with EV71 infection.