5-HT2 Receptors Facilitate JC Polyomavirus Entry
5-HT2 Receptors Facilitate JC Polyomavirus Entry
复制标题
DOI：
10.1128/jvi.02252-13
复制
发表时间：
2013-12-01
影响因子：
5.4
通讯作者：
Atwood, Walter J.
中科院分区：
文献类型：
--
作者：
Assetta, Benedetta;Maginnis, Melissa S.;Atwood, Walter J.
人类JC多瘤病毒(JCPyV)可引起进展性脱髓鞘疾病进行性多灶性白质脑病(PML)。这种疾病最常发生在艾滋病患者身上，但也会发生在接受免疫调节治疗的多发性硬化症等免疫相关疾病的患者身上。JCPyV感染宿主细胞需要五糖系列四糖c(LSTc)和5-羟色胺(5-HT)受体5-HT2AR。虽然LSTc通过与VP1的相互作用参与病毒与细胞的初始附着，但5-HT2AR促进感染的机制尚不清楚。为了进一步明确5-羟色胺受体在感染中的作用，将14种不同亚型的5-羟色胺受体基因导入对JCPyV不敏感的HEK293A细胞。只有5-HT2受体支持JCPyV感染。其他11种5-羟色胺受体亚型均不支持JCPyV感染。5-HT2受体的表达并没有增加JCPyV与细胞的结合，但这并不出人意料，因为细胞统一表达主要附着受体LSTc。这些细胞的感染对可溶性LSTc的抑制仍然敏感，证实了JCPyV感染需要识别LSTc。当表达5HT(2)受体时，病毒在HEK293A细胞中的内化显著且特异地增强。综上所述，这些数据证实了碳水化合物LSTc是JCPyV的附着受体，而2型5-羟色胺受体通过促进进入而促进JCPyV感染。
The human JC polyomavirus (JCPyV) causes the rapidly progressing demyelinating disease progressive multifocal leukoencephalopathy (PML). The disease occurs most often in individuals with AIDS but also occurs in individuals receiving immunomodulatory therapies for immune-related diseases such as multiple sclerosis. JCPyV infection of host cells requires the pentasaccharide lactoseries tetrasaccharide c (LSTc) and the serotonin receptor 5-hydroxytryptamine (5-HT) receptor 5-HT2AR. While LSTc is involved in the initial attachment of virus to cells via interactions with VP1, the mechanism by which 5-HT2AR contributes to infection is not clear. To further define the roles of serotonin receptors in infection, HEK293A cells, which are poorly permissive to JCPyV, were transfected with 14 different isoforms of serotonin receptor. Only 5-HT2 receptors were found to support infection by JCPyV. None of the other 11 isoforms of serotonin receptor supported JCPyV infection. Expression of 5-HT2 receptors did not increase binding of JCPyV to cells, but this was not unexpected, given that the cells uniformly expressed the major attachment receptor, LSTc. Infection of these cells remained sensitive to inhibition with soluble LSTc, confirming that LSTc recognition is required for JCPyV infection. Virus internalization into HEK293A cells was significantly and specifically enhanced when 5HT(2) receptors were expressed. Taken together, these data confirm that the carbohydrate LSTc is the attachment receptor for JCPyV and that the type 2 serotonin receptors contribute to JCPyV infection by facilitating entry.