Abstract：
Despite epidermal turnover, the skin is host to a complex array of microbes including viruses, such as the human papillomavirus (HPV), which must infect and manipulate skin keratinocyte stem cells (KSC) to survive. This crosstalk between the virome and KSC populations remains largely unknown. Here, we investigated the effect of HPV8 on KSCs using various mouse models. We observed that the HPV8 early region gene E6 specifically caused Lrig1+ hair follicle junctional zone KSC proliferation and expansion, which would facilitate viral transmission. Within Lrig1+ KSCs specifically, HPV8 E6 bound intracellular p300 to phosphorylate the STAT3 transcriptional regulatory node. This induces ΔNp63 expression, resulting in KSC expansion into the overlying epidermis. HPV8 was associated with 70% of human actinic keratoses (AK). Together these results define the \"hit and run\" mechanism for HPV8 in human actinic keratosis as an expansion of KSCs, which lacks melanosome protection and is thus susceptible to sun-light-induced malignant transformation.
摘要：
尽管表皮更新，皮肤是包括病毒在内的一系列复杂微生物的宿主，例如人乳头瘤病毒（HPV），必须感染和操纵皮肤角质形成细胞干细胞（KSC）才能存活。病毒和KSC群体之间的这种串扰在很大程度上仍然未知。这里,我们使用各种小鼠模型研究了HPV8对KSC的影响。我们观察到HPV8早期区基因E6特异性引起Lrig1+毛囊交界区KSC的增殖和扩张，这将促进病毒传播。特别是在Lrig1+KSC内，HPV8E6结合细胞内p300以磷酸化STAT3转录调节节点。这诱导ΔNp63表达，导致KSC扩张到上覆的表皮。HPV8与70%的人类光化性角化病(AK)相关。这些结果共同定义了人类光化性角化病中HPV8的“命中和运行”机制，作为KSC的扩增，缺乏黑素体保护，因此容易受到阳光诱导的恶性转化。
