Mucosal Human Defensins 5 and 6 Antagonize the Anti-HIV Activity of Candidate Polyanion Microbicides
Mucosal Human Defensins 5 and 6 Antagonize the Anti-HIV Activity of Candidate Polyanion Microbicides
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DOI：
10.1159/000322355
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发表时间：
2011-01-01
影响因子：
5.3
通讯作者：
Chang, Theresa L.
中科院分区：
文献类型：
--
作者：
Ding, Jian;Rapista, Aprille;Chang, Theresa L.
防御素是女性生殖器粘膜中含量非常丰富的抗菌肽。我们之前已经证明，由宫颈阴道上皮细胞产生的人类防御素5和6(HD5和HD6)在体外显著增强HIV的感染性。候选多阴离子杀菌剂包括PRO 2000、硫酸纤维素和卡拉胶，在大规模临床试验中未能保护女性免受艾滋病毒感染，但无效的分子基础尚不清楚。我们推测，粘膜宿主因子如HD5和HD6可能改变多阴离子杀菌剂抗HIV的活性。结果表明，HD5和HD6体外拮抗PRO 2000、硫酸纤维素和卡拉胶的抗HIV活性，但不能拮抗它们的线性类似物。多阴离子杀菌剂也降低了这些防御素对艾滋病毒的增强作用。我们的结论是，粘膜宿主因素可能会对局部杀微生物剂的疗效产生负面影响，在临床前评估中需要考虑它们对候选杀菌剂活性的影响。版权所有(C)2010年S.Karger AG，巴塞尔
Defensins are highly abundant antimicrobial peptides in the female genital mucosa. We have previously shown that human defensins 5 and 6 (HD5 and HD6), produced by cervicovaginal epithelial cells, significantly enhance HIV infectivity in vitro. Candidate polyanion microbicides, including PRO 2000, cellulose sulfate and carrageenan, failed to protect women against HIV infection in large-scale clinical trials, but the molecular basis of ineffectiveness was not clear. We hypothesized that mucosal host factors such as HD5 an HD6 may alter the activity of polyanion microbicides against HIV. Our results demonstrated that HD5 and HD6 but not their linear analogs antagonized the anti-HIV activity of PRO 2000, cellulose sulfate and carrageenan in vitro. Polyanion microbicides also reduced the HIV-enhancing effect of these defensins. We conclude that mucosal host factors could negatively impact the efficacy of topical microbicides against HIV, and their impact on the activity of candidate microbicides needs to be considered during the preclinical evaluation. Copyright (c) 2010 S. Karger AG, Basel