Genital transmission of HPV in a mouse model is potentiated by nonoxynol-9 and inhibited by carrageenan
Genital transmission of HPV in a mouse model is potentiated by nonoxynol-9 and inhibited by carrageenan
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DOI：
10.1038/nm1598
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发表时间：
2007-07-01
期刊：
影响因子：
82.9
通讯作者：
Schiller, John T.
中科院分区：
文献类型：
--
作者：
Roberts, Jeffrey N.;Buck, Christopher B.;Schiller, John T.
生殖器人乳头瘤病毒（HPV）感染是最常见的性传播感染，几乎所有宫颈癌病例都可归因于HPV亚群的感染（参考文献1）。尽管HPV感染的发病率很高，而且最近开发了一种预防性疫苗，可以保护人们免受某些HPV类型的感染，但人们对HPV感染的许多特征知之甚少。仍然值得考虑针对生殖器HPV的其他干预措施，特别是针对目前疫苗无法预防的感染的干预措施。然而，生产性乳头瘤病毒感染是物种和组织限制的，传统模型使用感染皮肤或口腔粘膜的动物乳头瘤病毒。在这里，我们报告的发展，小鼠模型的宫颈阴道感染HPV 16，重现了建立阶段的乳头瘤病毒感染。HPV 16假病毒转导报告基因的特点是组织学和量化的全器官，多光谱成像。感染需要破坏生殖器复层或柱状上皮的完整性，这发生在病毒沉积在基底角质形成细胞下面的基底膜上之后。广泛使用的阴道杀精剂壬苯醇醚-9（N-9）大大增加了感染的易感性。相比之下，角叉菜胶，一种存在于一些阴道润滑剂中的多糖，即使在N-9存在下也能预防感染，这表明角叉菜胶可能是一种有效的局部HPV杀微生物剂。
Genital human papillomavirus (HPV) infection is the most common sexually transmitted infection, and virtually all cases of cervical cancer are attributable to infection by a subset of HPVs (reviewed in ref. 1). Despite the high incidence of HPV infection and the recent development of a prophylactic vaccine that confers protection against some HPV types, many features of HPV infection are poorly understood. It remains worthwhile to consider other interventions against genital HPVs, particularly those that target infections not prevented by the current vaccine. However, productive papillomavirus infection is species- and tissue-restricted, and traditional models use animal papillomaviruses that infect the skin or oral mucosa. Here we report the development of a mouse model of cervicovaginal infection with HPV16 that recapitulates the establishment phase of papillomavirus infection. Transduction of a reporter gene by an HPV16 pseudovirus was characterized by histology and quantified by whole-organ, multispectral imaging. Disruption of the integrity of the stratified or columnar genital epithelium was required for infection, which occurred after deposition of the virus on the basement membrane underlying basal keratinocytes. A widely used vaginal spermicide, nonoxynol-9 (N-9), greatly increased susceptibility to infection. In contrast, carrageenan, a polysaccharide present in some vaginal lubricants, prevented infection even in the presence of N-9, suggesting that carrageenan might serve as an effective topical HPV microbicide.