Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, 50603, Malaysia.
Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, 50603, Malaysia.
Sci Rep. 2017 Mar 21;7:45069. doi: 10.1038/srep45069.
Hand-foot-and-mouth disease is a self-limiting paediatric infectious disease commonly caused by Enterovirus A71 (Genus: Enterovirus, Family: Picornaviridae). Typical lesions in and around the hands, feet, oral cavity and other places may rarely be complicated by acute flaccid paralysis and acute encephalomyelitis. Although virus is readily cultured from skin vesicles and oral secretions, the cellular target/s of Enterovirus A71 in human skin and oral mucosa are unknown. In Enterovirus A71-infected human skin and oral mucosa organotypic cultures derived from the prepuce and lip biopsies, focal viral antigens and viral RNA were localized to cytoplasm of epidermal and mucosal squamous cells as early as 2 days post-infection. Viral antigens/RNA were associated with cytoplasmic vacuolation and cellular necrosis. Infected primary prepuce epidermal keratinocyte cultures showed cytopathic effects with concomitant detection of viral antigens from 2 days post-infection. Supernatant and/or tissue homogenates from prepuce skin organotypic cultures and primary prepuce keratinocyte cultures showed viral titres consistent with active viral replication. Our data strongly support Enterovirus A71 squamous epitheliotropism in the human epidermis and oral mucosa, and suggest that these organs are important primary and/or secondary viral replication sites that contribute significantly to oral and cutaneous viral shedding resulting in person-to-person transmission, and viraemia, which could lead to neuroinvasion.
手足口病是一种自限性的儿科传染病，通常由肠道病毒 A71（属：肠道病毒，科：小核糖核酸病毒科）引起。手、脚、口腔及其他部位的典型病变很少并发急性弛缓性麻痹和急性脑脊髓炎。虽然病毒容易从皮肤疱疹和口腔分泌物中培养出来，但肠道病毒 A71 在人类皮肤和口腔黏膜中的细胞靶标尚不清楚。在来源于包皮和唇活检的人包皮和口腔黏膜器官型培养物中，感染肠道病毒 A71 后 2 天，即可在表皮和黏膜鳞状细胞的细胞质中定位到点状病毒抗原和病毒 RNA。病毒抗原/RNA 与细胞质空泡和细胞坏死有关。受感染的原代包皮表皮角质形成细胞培养物在感染后 2 天出现细胞病变效应，并同时检测到病毒抗原。包皮皮肤器官型培养物和原代包皮角质形成细胞培养物的上清液和/或组织匀浆显示出与活跃病毒复制一致的病毒滴度。我们的数据强烈支持肠道病毒 A71 在人类表皮和口腔黏膜中的鳞状上皮嗜性，并表明这些器官是重要的原发性和/或继发性病毒复制部位，这些部位在导致人与人之间传播的口腔和皮肤病毒脱落以及导致神经入侵的病毒血症中起重要作用。
