Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB8 9UP, United Kingdom.
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB8 9UP, United Kingdom.
Curr Opin Virol. 2021 Dec;51:96-105. doi: 10.1016/j.coviro.2021.09.014. Epub 2021 Oct 8.
Human papillomaviruses establish a reservoir of infection in the epithelial basal layer. To do this they limit their gene expression to avoid immune detection and modulate epithelial homeostasis pathways to inhibit the timing of basal cell delamination and differentiation to favour persistence. For low-risk Alpha papillomaviruses, which cause benign self-limiting disease in immunocompetent individuals, it appears that cell competition at the lesion edge restricts expansion. These lesions may be considered as self-regulating homeostatic structures, with epithelial cells of the hair follicles and sweat glands, which are proposed targets of the Beta and Mu papillomaviruses, showing similar restrictions to their expansion across the epithelium as a whole. In the absence of immune control, which facilitates deregulated viral gene expression, such lesions can expand, leading to problematic papillomatosis in afflicted individuals. By contrast, he high-risk Alpha HPV types can undergo deregulated viral gene expression in immunocompetent hosts at a number of body sites, including the cervical transformation zone (TZ) where they can drive the formation of neoplasia. Homeostasis at the TZ is poorly understood, but involves two adjacent epithelial cell population, one of which has the potential to stratify and to produce a multilayed squamous epithelium. This process of metaplasia involves a specialised cell type known as the reserve cell, which has for several decades been considered as the cell of origin of cervical cancer. It is becoming clear that during evolution, HPV gene products have acquired functions directly linked to their requirements to modify the normal processes of epithelial homestasis at their various sites of infection. These protein functions are beginning to provide new insight into homeostasis regulation at different body sites, and are likely to be central to our understanding of HPV epithelial tropisms.
人乳头瘤病毒（HPV）在表皮基底层建立感染库。为了做到这一点，它们限制了基因表达，以避免免疫检测，并调节上皮稳态途径，抑制基底细胞分层和分化的时间，以利于持续存在。对于低危型α型 HPV，它们在免疫功能正常的个体中引起良性自限性疾病，似乎病变边缘的细胞竞争限制了其扩张。这些病变可以被认为是自我调节的稳态结构，毛囊和汗腺的上皮细胞，它们是β型和μ型 HPV 的潜在靶标，其扩张受到类似的限制，遍及整个上皮。在没有免疫控制的情况下，病毒基因表达失调，这种病变可能会扩大，导致受影响个体出现问题性乳头瘤病。相比之下，在许多身体部位，包括宫颈转化区（TZ），免疫功能正常的宿主中高危型α HPV 可以发生失调的病毒基因表达，在那里它们可以驱动肿瘤的形成。TZ 的稳态尚不清楚，但涉及两个相邻的上皮细胞群体，其中一个具有分层和产生多层鳞状上皮的潜力。这个化生过程涉及一种特殊的细胞类型，称为储备细胞，几十年来，它一直被认为是宫颈癌的起源细胞。越来越清楚的是，在进化过程中，HPV 基因产物获得了与它们在不同感染部位改变上皮稳态正常过程直接相关的功能。这些蛋白功能开始为不同身体部位的稳态调节提供新的见解，并可能是我们理解 HPV 上皮嗜性的核心。
