Christensen Neil D
The Jake Gittlen Laboratories for Cancer Research, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Microb Cell. 2016 Sep 5;3(9):476-490. doi: 10.15698/mic2016.09.530.
Human papillomaviruses (HPVs) represent a large collection of viral types associated with significant clinical disease of cutaneous and mucosal epithelium. HPV-associated cancers are found in anogenital and oral mucosa, and at various cutaneous sites. Papillomaviruses are highly species and tissue restricted, and these viruses display both mucosotropic, cutaneotropic or dual tropism for epithelial tissues. A subset of HPV types, predominantly mucosal, are also oncogenic and cancers with these HPV types account for more than 200,000 deaths world-wide. Host control of HPV infections requires both innate and adaptive immunity, but the viruses have developed strategies to escape immune detection. Viral proteins can disrupt both innate pathogen-sensing pathways and T-cell based recognition and subsequent destruction of infected tissues. Current treatments to manage HPV infections include mostly ablative strategies in which recurrences are common and only active disease is treated. Although much is known about the papillomavirus life cycle, viral protein functions, and immune responsiveness, we still lack knowledge in a number of key areas of PV biology including tissue tropism, site-specific cancer progression, codon usage profiles, and what are the best strategies to mount an effective immune response to the carcinogenic stages of PV disease. In this review, disease transmission, protection and control are discussed together with questions related to areas in PV biology that will continue to provide productive opportunities of discovery and to further our understanding of this diverse set of human viral pathogens.
人乳头瘤病毒(HPV)是一大类与皮肤和黏膜上皮显著临床疾病相关的病毒类型。HPV相关癌症见于肛门生殖器和口腔黏膜以及各种皮肤部位。乳头瘤病毒具有高度的物种和组织限制性,这些病毒对上皮组织表现出亲黏膜性、亲皮肤性或双重嗜性。一部分HPV类型,主要是黏膜型,也具有致癌性,全球范围内由这些HPV类型导致的癌症死亡人数超过20万。宿主对HPV感染的控制需要先天免疫和适应性免疫,但病毒已发展出逃避免疫检测的策略。病毒蛋白可破坏先天病原体感应途径以及基于T细胞的识别和随后对感染组织的破坏。目前治疗HPV感染的方法主要包括消融策略,其中复发很常见,且仅治疗活动性疾病。尽管我们对乳头瘤病毒的生命周期、病毒蛋白功能和免疫反应性了解很多,但在乳头瘤病毒生物学的一些关键领域我们仍缺乏认识,包括组织嗜性、特定部位癌症进展、密码子使用概况,以及对乳头瘤病毒疾病致癌阶段产生有效免疫反应的最佳策略是什么。在这篇综述中,我们将讨论疾病传播、保护和控制,以及与乳头瘤病毒生物学领域相关的问题,这些问题将继续提供富有成效的发现机会,并加深我们对这一多样的人类病毒病原体的理解。