Herpes simplex virus type 1 enters human epidermal keratinocytes, but not neurons, via a pH-dependent endocytic pathway
Herpes simplex virus type 1 enters human epidermal keratinocytes, but not neurons, via a pH-dependent endocytic pathway
复制标题
DOI：
10.1128/jvi.79.12.7609-7616.2005
复制
发表时间：
2005-06-01
影响因子：
5.4
通讯作者：
Straus, SE
中科院分区：
文献类型：
--
作者：
Nicola, AV;Hou, J;Straus, SE
单纯疱疹病毒（HSV）通过pH依赖性内吞机制进入某些实验室细胞系。我们研究了这种进入途径是否用于与发病机制相关的人类细胞类型。三种不同类型的亲溶酶体剂，提高内体pH值，阻止HSV进入原代和转化的人角质形成细胞，但不进入人神经元或神经母细胞瘤系。在角质形成细胞中，传入的HSV颗粒与内吞摄取的标记物共定位。用蛋白酪氨酸激酶抑制剂异黄酮治疗，减少了传入的病毒颗粒到细胞核周围的传递和角质形成细胞中病毒诱导的基因表达，但不是神经元。此外，在角质形成细胞单层胰岛中，HSV以染料木黄酮敏感的方式感染内细胞和外细胞，表明基底外侧和顶端质膜表面的病毒内吞作用。总之，结果表明HSV通过依赖于宿主酪氨酸磷酸化的低pH内吞途径进入人表皮角质形成细胞，而不是神经元。因此，HSV利用根本不同的细胞进入途径感染重要的靶细胞群体。
Herpes simplex virus (HSV) enters some laboratory cell lines via a pH-dependent, endocytic mechanism. We investigated whether this entry pathway is used in human cell types relevant to pathogenesis. Three different classes of lysosomotropic agents, which raise endosomal pH, blocked HSV entry into primary and transformed human keratinocytes, but not into human neurons or neuroblastoma lines. In keratinocytes, incoming HSV particles colocalized with markers of endocytic uptake. Treatment with the isoflavone genistein, an inhibitor of protein tyrosine kinases, reduced the delivery of incoming viral particles to the nuclear periphery and virus-induced gene expression in keratinocytes but not neurons. Moreover, in keratinocyte monolayer islets, HSV infected both the inner and outer cells in a genistein-sensitive manner, suggesting viral endocytosis from both basolateral and apical plasma membrane surfaces. Together, the results indicate that HSV enters human epidermal keratinocytes, but not neurons, by a low-pH, endocytic pathway that is dependent on host tyrosine phosphorylation. Thus, HSV utilizes fundamentally different cellular entry pathways to infect important target cell populations.