Carrageenan is a potent inhibitor of papillomavirus infection.
Carrageenan is a potent inhibitor of papillomavirus infection.
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DOI：
10.1371/journal.ppat.0020069
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发表时间：
2006-07
期刊：
影响因子：
6.7
通讯作者：
Schiller JT
中科院分区：
文献类型：
--
作者：
Buck CB;Thompson CD;Roberts JN;Müller M;Lowy DR;Schiller JT
某些性传播的人类乳头瘤病毒(HPV)类型与宫颈癌的发生有因果关系。我们最近开发的高滴度HPV伪病毒使我们能够进行高通量的体外筛选来识别HPV感染抑制剂。多种化合物的比较表明，卡拉胶是从红藻中提取的一种硫酸多糖，对广泛的性传播HPV具有极强的感染抑制作用。虽然卡拉胶在体外可以抑制单纯疱疹病毒和一些HIV毒株，但生殖器HPV的易感性约为1000倍，50%的抑制剂量在低ng/ml范围内。卡拉胶的作用主要是通过阻止HPV病毒粒子与细胞结合来发挥作用。这一发现与卡拉胶类似于HPV细胞附着因子硫酸乙酰肝素的事实一致。然而，卡拉胶的效力比肝素高三个数量级，肝素是一种无细胞硫酸肝素，被认为是一种高效的HPV抑制剂。卡拉胶还可以通过第二种不依赖于硫酸肝素的作用来阻断HPV感染。卡拉胶被广泛用作各种化妆品和食品的增稠剂，从性润滑剂到婴儿配方奶粉。其中一些产品在体外可以阻止HPV的传染性，即使稀释了一百万倍也是如此。需要进行临床试验，以确定卡拉胶产品作为局部杀菌剂是否对生殖器HPV有效。性传播的人类乳头瘤病毒(HPV)感染非常常见。虽然大多数HPV感染不会引起明显的症状，但某些生殖器HPV类型的持续感染可能会导致宫颈癌或其他肛门/生殖器癌症。另一种类型的HPV可能会导致生殖器疣。最近的研究表明，避孕套在预防HPV感染方面并不是非常有效。尽管HPV疫苗将很快上市，但它们可能无法预防所有生殖器HPV类型，而且在发展中国家使用起来过于昂贵。廉价的HPV抑制化合物(称为局部杀微生物剂)可能有助于阻止HPV的传播。使用一种新开发的基于细胞培养的HPV抑制试验，我们发现一种名为卡拉胶的廉价胶凝剂是一种出人意料的有效的HPV感染抑制剂。卡拉胶作为一种针对艾滋病毒和疱疹病毒的局部杀菌剂也在研究中，但在细胞培养测试中，它对HPV的效果要高出一千倍。有趣的是，卡拉胶被用作一些商品性润滑剂和润滑避孕套的增稠剂。在我们的细胞培养-感染系统中，这些商用润滑油产品中有几种是有效的HPV抑制剂。需要临床试验来确定卡拉胶作为一种局部杀菌剂对抗HPV的有效性。
Certain sexually transmitted human papillomavirus (HPV) types are causally associated with the development of cervical cancer. Our recent development of high-titer HPV pseudoviruses has made it possible to perform high-throughput in vitro screens to identify HPV infection inhibitors. Comparison of a variety of compounds revealed that carrageenan, a type of sulfated polysaccharide extracted from red algae, is an extremely potent infection inhibitor for a broad range of sexually transmitted HPVs. Although carrageenan can inhibit herpes simplex viruses and some strains of HIV in vitro, genital HPVs are about a thousand-fold more susceptible, with 50% inhibitory doses in the low ng/ml range. Carrageenan acts primarily by preventing the binding of HPV virions to cells. This finding is consistent with the fact that carrageenan resembles heparan sulfate, an HPV cell-attachment factor. However, carrageenan is three orders of magnitude more potent than heparin, a form of cell-free heparan sulfate that has been regarded as a highly effective model HPV inhibitor. Carrageenan can also block HPV infection through a second, postattachment heparan sulfate–independent effect. Carrageenan is in widespread commercial use as a thickener in a variety of cosmetic and food products, ranging from sexual lubricants to infant feeding formulas. Some of these products block HPV infectivity in vitro, even when diluted a million-fold. Clinical trials are needed to determine whether carrageenan-based products are effective as topical microbicides against genital HPVs. Sexually transmitted human papillomavirus (HPV) infections are very common. Although most HPV infections don't cause noticeable symptoms, persistent infection with some genital HPV types can lead to cervical cancer or other anal/genital cancers. Another subset of HPV types can cause genital warts. Recent studies have suggested that condoms are not highly effective in preventing HPV infection. Although HPV vaccines will soon become available, they probably will not protect against all genital HPV types and will be too expensive for use in the developing world. Inexpensive HPV-inhibitory compounds (known as topical microbicides) might be useful for blocking the spread of HPV. Using a newly developed cell culture–based HPV inhibition test, we have discovered that an inexpensive gelling agent called carrageenan is an unexpectedly potent HPV infection inhibitor. Carrageenan is also under investigation as a topical microbicide targeting HIV and herpes viruses, but it is a thousand times more effective against HPV in cell culture tests. Interestingly, carrageenan is used as a thickener in some commercially available sexual lubricants and lubricated condoms. Several of these commercial lubricant products are potent HPV inhibitors in our cell culture–infection system. Clinical trials are needed to determine the effectiveness of carrageenan as a topical microbicide against HPV.
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