Inhibitory effect of PRO 2000, a candidate microbicide, on dendritic cell-mediated human immunodeficiency virus transfer.
Inhibitory effect of PRO 2000, a candidate microbicide, on dendritic cell-mediated human immunodeficiency virus transfer.
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PRO 2000（一种候选杀菌剂）对树突状细胞介导的人类免疫缺陷病毒传播的抑制作用。
DOI：
10.1128/aac.00707-07
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发表时间：
2008
影响因子：
4.9
通讯作者：
Klotman,MaryE
中科院分区：
文献类型：
--
作者：
Teleshova,Natalia;Chang,Theresa;Profy,Albert;Klotman,MaryE
由于没有有效的预防人类免疫缺陷病毒（HIV）感染的疫苗，开发局部杀微生物剂已成为当务之急。磺化聚阴离子PRO 2000是一种候选的局部杀微生物剂，目前正处于II/III期临床试验中，可在体外阻断宫颈组织的HIV感染。树突状细胞（DC）是最早接触生殖道中的HIV并促进病毒传播的细胞类型之一。因此，干扰病毒-DC相互作用是局部杀微生物剂的期望特征，只要其不干扰DC的正常功能。PRO 2000在单核细胞衍生DC（MDDC）捕获复制缺陷型HIV/RFL报告病毒或复制能力型HIV/BaL期间存在，抑制随后HIV转移至靶细胞。在MDDC-靶细胞共培养期间持续暴露于PRO 2000有效地抑制了靶细胞的HIV感染。PRO 2000抑制MDDC捕获HIV。此外，该化合物阻断了R5和X4 HIV病毒介导的细胞-细胞融合。有趣的是，同时暴露于PRO 2000和脂多糖减弱了响应于刺激的细胞因子产生，表明该化合物改变了DC功能。虽然在高度容许的MDDC-T细胞环境中有效阻断MDDC介导的病毒转移和感染增强了PRO 2000作为抗HIV的局部杀微生物剂的潜在价值，但PRO 2000对免疫细胞功能的影响值得仔细评估。
Without an effective vaccine against human immunodeficiency virus (HIV) infection, topical microbicide development has become a priority. The sulfonated polyanion PRO 2000, a candidate topical microbicide now in phase II/III clinical trials, blocks HIV infection of cervical tissue in vitro. Dendritic cells (DC) are among the first cell types to contact HIV in the genital tract and facilitate the spread of the virus. Thus, interfering with virus-DC interactions is a desirable characteristic of topical microbicides as long as that does not interfere with the normal function of DC. PRO 2000 present during capture of the replication-defective HIVJRFLreporter virus or replication-competent HIVBaLby monocyte-derived DC (MDDC) inhibited subsequent HIV transfer to target cells. Continuous exposure to PRO 2000 during MDDC-target cell coculture effectively inhibited HIV infection of target cells. PRO 2000 inhibited HIV capture by MDDC. In addition, the compound blocked R5 and X4 HIV envelope-mediated cell-cell fusion. Interestingly, simultaneous exposure to PRO 2000 and lipopolysaccharide attenuated the cytokine production in response to stimulation, suggesting that the compound altered DC function. While efficient blocking of MDDC-mediated virus transfer and infection in the highly permissive MDDC-T-cell environment reinforces the potential value of PRO 2000 as a topical microbicide against HIV, the impact of PRO 2000 on immune cell functions warrants careful evaluation.