Saijets Salla, Ylipaasto Petri, Vaarala Outi, Hovi Tapani, Roivainen Merja
Enterovirus Laboratory, National Public Health Institute (KTL), Helsinki, Finland.
J Med Virol. 2003 Jul;70(3):430-9. doi: 10.1002/jmv.10413.
Gastrointestinal tract associated lymphoid tissue is considered to be the main replication site for enteroviruses. In order to invade tissues to reach pancreatic islets, cardiac muscles, and other secondary replication sites, the virus has to survive circulation in the blood and find a way to get through endothelial cells. In the present study, the susceptibility of human endothelial cells to infections caused by human parechovirus 1 and several prototype strains of enteroviruses, representing different species (human poliovirus, human enterovirus B and C), and acting through different receptor families was examined. Primary endothelial cells isolated from human umbilical vein by collagenase perfusion and also an established human endothelial cell line, HUVEC, were used. Primary endothelial cells were highly susceptible to several serotypes of enteroviruses (coxsackievirus A13, echoviruses 6, 7, 11, 30, and poliovirus 1). However, coxsackievirus A 9 and echovirus 1 infected only a few individual cells while human parechovirus 1 and coxsackie B viruses did not show evidence of replication in primary endothelial cells. In general, primary endothelial cells were more sensitive to infection-induced cytolytic effect than HUVEC. Activation of endothelial cells by interleukin-1beta did not change the pattern of enterovirus infection. Immunofluorescence stainings of infected primary endothelial cells showed that expression of activation markers, E-selectin, and intercellular adhesion molecule-1, was clearly increased by several virus infections and the former molecule also by exposing cells to UV-light inactivated coxsackieviruses. In contrast, human leukocyte antigen-DR expression was not increased by virus infection.
胃肠道相关淋巴组织被认为是肠道病毒的主要复制部位。为了侵入组织到达胰岛、心肌和其他次要复制部位，病毒必须在血液循环中存活并找到穿过内皮细胞的方法。在本研究中，检测了人内皮细胞对1型人细小病毒及几种代表不同种属（人脊髓灰质炎病毒、人肠道病毒B和C）且通过不同受体家族起作用的肠道病毒原型株感染的易感性。使用了通过胶原酶灌注从人脐静脉分离的原代内皮细胞以及已建立的人内皮细胞系HUVEC。原代内皮细胞对几种肠道病毒血清型（柯萨奇病毒A13、埃可病毒6、7、11、30和脊髓灰质炎病毒1）高度敏感。然而，柯萨奇病毒A9和埃可病毒1仅感染了少数单个细胞，而1型人细小病毒和柯萨奇B病毒在原代内皮细胞中未显示复制迹象。一般来说，原代内皮细胞比HUVEC对感染诱导的细胞溶解作用更敏感。白细胞介素-1β对内皮细胞的激活并未改变肠道病毒感染模式。对感染的原代内皮细胞进行免疫荧光染色显示，几种病毒感染明显增加了激活标志物E选择素和细胞间黏附分子-1的表达，并且将细胞暴露于紫外线灭活的柯萨奇病毒也增加了前一种分子的表达。相反，病毒感染并未增加人白细胞抗原-DR的表达。
