Martino T A, Petric M, Weingartl H, Bergelson J M, Opavsky M A, Richardson C D, Modlin J F, Finberg R W, Kain K C, Willis N, Gauntt C J, Liu P P
Heart and Stroke/Richard Lewar Center of Excellence, University of Toronto, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada.
Virology. 2000 May 25;271(1):99-108. doi: 10.1006/viro.2000.0324.
Group B coxsackieviruses are etiologically linked to many human diseases, and cell surface receptors are postulated to play an important role in mediating their pathogenesis. The coxsackievirus adenovirus receptor (CAR) has been shown to function as a receptor for selected strains of coxsackievirus group B (CVB) serotypes 3, 4, and 5 and is postulated to serve as a receptor for all six serotypes. In this study, we demonstrate that CAR can serve as a receptor for laboratory reference strains and clinical isolates of all six CVB serotypes. Infection of CHO cells expressing human CAR results in a 1000-fold increase in CVB progeny virus titer compared to mock transfected cells. CAR was shown to be a functional receptor for swine vesicular disease virus (SVDV), as CHO-CAR cells but not CHO mock transfected controls were susceptible to SVDV infection, produced progeny SVDV, and developed cytopathic effects. Moreover, SVDV infection could be specifically blocked by monoclonal antibody to CAR (RmcB). SVDV infection of HeLa cells was also inhibited by an anti-CD55 MAb, suggesting that this virus, like some CVB, may interact with CD55 (decay accelerating factor) in addition to CAR. Finally, pretreatment of CVB or SVDV with soluble CAR effectively blocks virus infection of HeLa cell monolayers.
B组柯萨奇病毒与许多人类疾病存在病因学关联,据推测细胞表面受体在介导其发病机制中起重要作用。柯萨奇病毒腺病毒受体(CAR)已被证明可作为B组柯萨奇病毒(CVB)3、4和5型某些毒株的受体,据推测它也是所有六种血清型的受体。在本研究中,我们证明CAR可作为所有六种CVB血清型的实验室参考毒株和临床分离株的受体。与mock转染细胞相比,感染表达人CAR的CHO细胞会使CVB子代病毒滴度增加1000倍。CAR被证明是猪水疱病病毒(SVDV)的功能性受体,因为CHO - CAR细胞而非CHO mock转染对照对SVDV感染敏感,产生子代SVDV,并出现细胞病变效应。此外,抗CAR单克隆抗体(RmcB)可特异性阻断SVDV感染。抗CD55单克隆抗体也可抑制HeLa细胞的SVDV感染,这表明该病毒与某些CVB一样,除了与CAR相互作用外,可能还与CD55(衰变加速因子)相互作用。最后,用可溶性CAR预处理CVB或SVDV可有效阻断病毒对HeLa细胞单层的感染。