Keratinocyte-secreted laminin 5 can function as a transient receptor for human papillomaviruses by binding virions and transferring them to adjacent cells
Keratinocyte-secreted laminin 5 can function as a transient receptor for human papillomaviruses by binding virions and transferring them to adjacent cells
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DOI：
10.1128/jvi.00724-06
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发表时间：
2006-09-01
影响因子：
5.4
通讯作者：
Christensen, Neil D.
中科院分区：
文献类型：
--
作者：
Culp, Timothy D.;Budgeon, Lynn R.;Christensen, Neil D.
人乳头瘤病毒（hpv）仅在皮肤和粘膜的终末分化上皮中复制。虽然基底角化细胞的感染被认为是允许性感染的必要条件，但目前尚不清楚病毒粒子是否可以特异性地针对基底细胞进行吸附和摄取。我们提出的证据表明，HPV特异性结合层粘连蛋白5 (LN5)，细胞外基质（ECM）的一个组成部分，由迁移和基底角质形成细胞分泌。阴道角化细胞分泌的ECM中，HPV 11型衣壳与LN5共定位。通过抗LN5抗体预处理，可以有效阻断病毒粒子和病毒样颗粒与纯化LN5和培养的角质形成细胞分泌的富含LN5的ECM的结合。结合人宫颈粘膜切片的HPV衣壳包括含有LN5的基底膜。表达α 6整合素（一种已知与LN5结合的跨膜蛋白）的培养角质形成细胞很容易被预先吸附在含有LN5的底物上的病毒粒子感染，而缺乏α 6整合素的突变型角质形成细胞通过这种途径相对抵抗感染。这些发现提示了一种自然HPV感染模型，其中增殖的角质形成细胞在上皮损伤部位表达a6整合素，可能被迁移的角质形成细胞分泌的LN5短暂吸附的病毒粒子靶向。
Human papillomaviruses (HPVs) replicate only in the terminally differentiating epithelium of the skin and mucosa. While infection of basal keratinocytes is considered a requirement for permissive infection, it remains unclear whether virions can specifically target basal cells for adsorption and uptake following epithelial wounding. We present evidence that HPV binds specifically to laminin 5 (LN5), a component of the extracellular matrix (ECM) secreted by migrating and basal keratinocytes. HPV type 11 capsids colocalized with LN5 in the ECM secreted by vaginal keratinocytes. Binding of both virions and virus-like particles to purified LN5 and to the LN5-rich ECM secreted by cultured keratinocytes was effectively blocked by pretreatment with anti-LN5 antibodies. HPV capsid binding to human cervical mucosa sections included the basement membrane which contains LN5. Cultured keratinocytes expressing alpha 6 integrin, a transmembrane protein known to bind LN5, were readily infected by virions preadsorbed to LN5-containing substrates, whereas mutant keratinocytes lacking alpha 6 integrin were relatively resistant to infection via this route. These findings suggest a model of natural HPV infection in which proliferating keratinocytes expressing a6 integrin at the site of epithelial wounding might be targeted by virions adsorbed transiently to LN5 secreted by migrating keratinocytes.