Anti-Retroviral Protease Inhibitors Regulate Human Papillomavirus 16 Infection of Primary Oral and Cervical Epithelium.
Anti-Retroviral Protease Inhibitors Regulate Human Papillomavirus 16 Infection of Primary Oral and Cervical Epithelium.
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DOI：
10.3390/cancers12092664
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发表时间：
2020-09-18
期刊：
影响因子：
5.2
通讯作者：
Meyers C
中科院分区：
文献类型：
--
作者：
Alam S;Chatterjee S;Kang SD;Milici J;Biryukov J;Chen H;Meyers C
2016年，全球有3670万人感染了人类免疫缺陷病毒（HIV），其中53%的人获得了抗逆转录病毒治疗（ART）（联合国艾滋病规划署2017年全球艾滋病毒统计数据）。在抗逆转录病毒治疗时代，艾滋病毒感染者患人乳头瘤病毒（HPV）相关口咽癌、子宫颈癌和肛门癌的风险较高。一般来说，HPV感染是自限性的，然而，持续的HPV感染是致癌进展的主要风险。在最初感染和癌症发展之间的较长时间间隔意味着涉及辅因子。增加传染性、病毒载量和持久性的辅助因素增加了癌症的风险。我们提出ART蛋白酶抑制剂（PI）类药物是调节hiv感染患者HPV感染的新型辅助因子。我们建立了一个器官型上皮模型系统来研究PI治疗对HPV16感染的影响。我们的模型可用于研究抗逆转录病毒治疗背景下HPV感染的机制，并用于开发减少HPV感染的药物。流行病学研究表明，接受高效抗逆转录病毒治疗（HAART）的人类免疫缺陷病毒（HIV）感染患者获得机会性人乳头瘤病毒（HPV）感染和发展为口腔癌和宫颈癌的风险可能增加。有效的高效抗逆转录病毒疗法提高了生存率，但增加了hpv相关癌症的风险。在这篇论文中，我们报道了蛋白酶抑制剂（PI）处理来源于原代人牙龈和宫颈上皮细胞的三维组织，破坏了分层上皮内的细胞间连接，增强了HPV16向基底层感染的细胞旁通透性，最终通过5-溴-2 ' -去氧尿苷（BrdU）标记新合成的基因组来确定后代HPV16的从头生物合成。我们认为HAART/PI代表了一类调节HPV靶上皮感染的新型辅助因子。我们的体外组织培养模型是研究抗逆转录病毒药物促进HAART-naïve原代上皮中HPV感染的机制作用的重要工具。随后病毒载量的变化可能促进新的感染，产生增加病毒持久性的HPV库，并增加接受长期HAART治疗的hiv阳性患者发生口腔癌和宫颈癌的风险。
In 2016, globally, 36.7 million people were living with Human Immunodeficiency Virus (HIV), of which 53% had access to anti-retroviral therapy (ART) (UNAIDS 2017 Global HIV Statistics). The risk of Human Papillomavirus (HPV) associated oropharyngeal, cervical and anal cancers are higher among patients infected with HIV in the era of ART. Generally, HPV infections are self-limiting, however, persistent HPV infection is a major risk to carcinogenic progression. Long intervals between initial infection and cancer development imply cofactors are involved. Co-factors that increase infectivity, viral load, and persistence increase risk of cancer. We propose that the ART Protease Inhibitors (PI) class of drugs are novel co-factors that regulate HPV infection in HIV-infected patients. We developed a model system of organotypic epithelium to study impact of PI treatment on HPV16 infection. Our model could be used to study mechanisms of HPV infection in context of ART, and for developing drugs that minimize HPV infections. Epidemiology studies suggest that Human Immunodeficiency Virus (HIV)-infected patients on highly active anti-retroviral therapy (HAART) may be at increased risk of acquiring opportunistic Human Papillomavirus (HPV) infections and developing oral and cervical cancers. Effective HAART usage has improved survival but increased the risk for HPV-associated cancers. In this manuscript, we report that Protease Inhibitors (PI) treatment of three-dimensional tissues derived from primary human gingiva and cervical epithelial cells compromised cell-cell junctions within stratified epithelium and enhanced paracellular permeability of HPV16 to the basal layer for infection, culminating in de novo biosynthesis of progeny HPV16 as determined using 5-Bromo-2′-deoxyuridine (BrdU) labeling of newly synthesized genomes. We propose that HAART/PI represent a novel class of co-factors that modulate HPV infection of the target epithelium. Our in vitro tissue culture model is an important tool to study the mechanistic role of anti-retroviral drugs in promoting HPV infections in HAART-naïve primary epithelium. Changes in subsequent viral load could promote new infections, create HPV reservoirs that increase virus persistence, and increase the risk of oral and cervical cancer development in HIV-positive patients undergoing long-term HAART treatment.
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影响因子：
11.8
作者：
King, MD;Reznik, DA;Blumberg, HM
通讯作者：
Blumberg, HM
DOI：
10.1016/s2352-3018(17)30125-x
发表时间：
2017-11
期刊：
The lancet. HIV
影响因子：
--
作者：
Hernández-Ramírez RU;Shiels MS;Dubrow R;Engels EA
通讯作者：
Engels EA
影响因子：
5
作者：
Beachler, Daniel C.;Sugar, Elizabeth A.;D'Souza, Gypsyamber
通讯作者：
D'Souza, Gypsyamber
影响因子：
3.1
作者：
Cameron, JE;Mercante, D;Hagensee, ME
通讯作者：
Hagensee, ME
影响因子：
3.8
作者：
Greenwood, I;Zakrzewska, JM;Robinson, PG
通讯作者：
Robinson, PG