Human papillomavirus molecular biology and disease association.
Human papillomavirus molecular biology and disease association.
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DOI：
10.1002/rmv.1822
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发表时间：
2015-03
影响因子：
11.1
通讯作者：
Murakami, Isao
中科院分区：
文献类型：
--
作者：
Doorbar, John;Egawa, Nagayasu;Griffin, Heather;Kranjec, Christian;Murakami, Isao
人乳头瘤病毒（HPVs）经过数百万年的进化，在包括人类在内的多种不同动物物种中进行自我传播。以这种方式缓慢共同进化的病毒通常会引起慢性无症状感染，在无明显疾病症状的情况下产生病毒粒子。许多β型和γ型人乳头瘤病毒就是这种情况。然而，α型人乳头瘤病毒已经进化出免疫逃避策略，使其能够导致持续性的可见乳头瘤。这些病毒在受感染的上皮细胞分化时激活细胞周期，以创造一个有利于病毒基因组扩增并包装成感染性颗粒的复制适宜环境。这是由病毒的E6、E7和E5蛋白介导的。然而，高危型E6和E7蛋白与低危型的不同之处在于，它们能够促使上皮上层细胞进入细胞周期，并且还能刺激基底细胞层和旁基底细胞层的细胞增殖。在无法清除高危型人乳头瘤病毒感染的个体中，这些细胞周期调节因子的表达失调是肿瘤形成以及最终发展为癌症的基础。到目前为止，大多数研究都集中在对高危型人乳头瘤病毒，如HPV 16和18的研究上，这使得人们对这些病毒所利用的分子途径有了一定的了解。这些研究方法将促使人们开发出更好的疾病治疗策略，包括靶向抗病毒药物和免疫疗法。目前的研究重点是了解子宫颈以外部位（如扁桃体、其他转化区）的人乳头瘤病毒肿瘤形成，以及了解低危型人乳头瘤病毒有时如何导致乳头瘤病，在某些情况下甚至引发癌症的机制。版权所有© 2015约翰威立父子有限公司
Human papillomaviruses (HPVs) have evolved over millions of years to propagate themselves in a range of different animal species including humans. Viruses that have co‐evolved slowly in this way typically cause chronic inapparent infections, with virion production in the absence of apparent disease. This is the case for many Beta and Gamma HPV types. The Alpha papillomavirus types have however evolved immunoevasion strategies that allow them to cause persistent visible papillomas. These viruses activate the cell cycle as the infected epithelial cell differentiates in order to create a replication competent environment that allows viral genome amplification and packaging into infectious particles. This is mediated by the viral E6, E7, and E5 proteins. High‐risk E6 and E7 proteins differ from their low‐risk counterparts however in being able to drive cell cycle entry in the upper epithelial layers and also to stimulate cell proliferation in the basal and parabasal layers. Deregulated expression of these cell cycle regulators underlies neoplasia and the eventual progression to cancer in individuals who cannot resolve high‐risk HPV infection. Most work to date has focused on the study of high‐risk HPV types such as HPV 16 and 18, which has led to an understanding of the molecular pathways subverted by these viruses. Such approaches will lead to the development of better strategies for disease treatment, including targeted antivirals and immunotherapeutics. Priorities are now focused toward understanding HPV neoplasias at sites other than the cervix (e.g. tonsils, other transformation zones) and toward understanding the mechanisms by which low‐risk HPV types can sometimes give rise to papillomatosis and under certain situations even cancers. Copyright © 2015 John Wiley & Sons, Ltd.
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