Department of Pathology, School of Basic Medical Sciences, Peking University, Beijing, China.
Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Am J Pathol. 2014 Mar;184(3):714-20. doi: 10.1016/j.ajpath.2013.11.009. Epub 2013 Dec 27.
Enterovirus 71 (EV71; family Picornaviridae, species human Enterovirus A) usually causes hand, foot, and mouth disease, which may rarely be complicated by fatal encephalomyelitis. We investigated extra-central nervous system (extra-CNS) tissues capable of supporting EV71 infection and replication, and have correlated tissue infection with expression of putative viral entry receptors, scavenger receptor B2 (SCARB2), and P-selectin glycoprotein ligand-1 (PSGL-1). Formalin-fixed, paraffin-embedded CNS and extra-CNS tissues from seven autopsy cases were examined by IHC and in situ hybridization to evaluate viral antigens and RNA. Viral receptors were identified with IHC. In all seven cases, the CNS showed stereotypical distribution of inflammation and neuronal localization of viral antigens and RNA, confirming the clinical diagnosis of EV71 encephalomyelitis. In six cases in which tonsillar tissues were available, viral antigens and/or RNA were localized to squamous epithelium lining the tonsillar crypts. Tissues from the gastrointestinal tract, pancreas, mesenteric nodes, spleen, and skin were all negative for viral antigens/RNA. Our novel findings strongly suggest that tonsillar crypt squamous epithelium supports active viral replication and represents an important source of viral shedding that facilitates person-to-person transmission by both the fecal-oral or oral-oral routes. It may also be a portal for viral entry. A correlation between viral infection and SCARB2 expression appears to be more significant than for PSGL-1 expression.
肠道病毒 71 型（EV71；小核糖核酸病毒科，人肠道病毒 A 种）通常引起手足口病，极少数情况下可能并发致命性脑脊髓炎。我们研究了能够支持 EV71 感染和复制的中枢神经系统以外（extra-CNS）组织，并将组织感染与假定的病毒进入受体——清道夫受体 B2（SCARB2）和 P 选择素糖蛋白配体-1（PSGL-1）的表达相关联。通过免疫组化和原位杂交，对来自 7 例尸检病例的福尔马林固定、石蜡包埋的 CNS 和 extra-CNS 组织进行了检查，以评估病毒抗原和 RNA。用免疫组化鉴定了病毒受体。在所有 7 例病例中，CNS 均表现出炎症的典型分布和病毒抗原及 RNA 的神经元定位，从而证实了 EV71 脑脊髓炎的临床诊断。在 6 例可获得扁桃体组织的病例中，病毒抗原和/或 RNA 定位于扁桃体隐窝的鳞状上皮。胃肠道、胰腺、肠系膜淋巴结、脾脏和皮肤组织均未检测到病毒抗原/RNA。我们的新发现强烈表明，扁桃体隐窝的鳞状上皮支持活跃的病毒复制，是病毒脱落的重要来源，通过粪-口或口-口途径促进人与人之间的传播。它也可能是病毒进入的门户。病毒感染与 SCARB2 表达之间的相关性似乎比 PSGL-1 表达更为显著。
