Kawasaki disease (KD), a multi-system vasculitis of childhood that may result in aneurysms of the coronary arteries, is the most common cause of acquired heart disease in children in the developed world. The etiology of KD is unknown. We recently identified a novel human coronavirus, designated New Haven coronavirus (HCoV-NH) that was detected in 9% of children < 5 years old with respiratory tract disease who tested negative for common respiratory viruses. One child in this initial study was diagnosed with KD. A subsequent case-control study revealed that KD was associated with HCoV-NH; 8 of 11 children with KD (72.7%) and 1 of 22 matched controls (4.5%) tested positive for HCoV-NH (P=0.0015). This intriguing observation suggests that HCoV-NH may be the cause of KD and demands further investigation. A fundamental unanswered question is, """"""""what is different about the KD vs. the non-KD patients (children with respiratory tract infection) in response to infection with HCoV-NH?"""""""" Therefore, we will explore the following linked hypotheses: 1) that the nature of viral infection differs between KD and non-KD patients. We will determine the extent and duration of viral shedding, assay for viremia and determine whether HCoV-NH strains differ between KD and non-KD patients; 2) that there is a qualitative and/or quantitative difference in the immune response to infection with HCoV-NH between KD and non-KD patients. We will determine whether KD patients have a) higher antibody titer response to HCoV-NH, b) respond to HCoV-NH with different immunoglobulin classes and c) develop antibodies to different viral HCoV-NH proteins vs. non-KD patient controls. KD and non-KD patients for these studies will be identified prospectively and; 3) that diseased tissue in KD patients contains HCoV-NH, which is responsible for the pathology observed in KD. We will develop tools to detect HCoV-NH antigens in tissue. Antibodies developed against whole virus and the major antigenic proteins of HCoV-NH will be used in immunohistochemical studies. We will also determine whether the synthetic antibody developed by Rowley et al., that bound to an unknown antigen in respiratory epithelial cells and macrophages from children with KD, is specific for HCoV-NH. These studies will help illuminate the role of HCoV-NH in KD and ultimately may lead to improved therapies and strategies to prevent KD. Description: KD is the leading cause of acquired heart disease in children. We have identified a novel human virus, designated the New Haven coronavirus that is associated with KD. The goals of this study is to investigate the role of this novel virus in KD. ? ?

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-CICS (01))
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Cassels, Frederick J
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Yale University
Schools of Medicine
New Haven
United States
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Shao, Xiuping; Guo, Xiaojie; Esper, Frank et al. (2007) Seroepidemiology of group I human coronaviruses in children. J Clin Virol 40:207-13