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首页> 外文期刊>AIDS Research and Human Retroviruses >Short communication: a repeated simian human immunodeficiency virus reverse transcriptase/herpes simplex virus type 2 cochallenge macaque model for the evaluation of microbicides.
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Short communication: a repeated simian human immunodeficiency virus reverse transcriptase/herpes simplex virus type 2 cochallenge macaque model for the evaluation of microbicides.

机译:简短交流:重复的猿猴人免疫缺陷病毒逆转录酶/单纯疱疹病毒2型耳蜗猕猴模型用于评估杀菌剂。

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Epidemiological studies suggest that prevalent herpes simplex virus type 2 (HSV-2) infection increases the risk of HIV acquisition, underscoring the need to develop coinfection models to evaluate promising prevention strategies. We previously established a single high-dose vaginal coinfection model of simian human immunodeficiency virus (SHIV)/HSV-2 in Depo-Provera (DP)-treated macaques. However, this model does not appropriately mimic women's exposure. Repeated limiting dose SHIV challenge models are now used routinely to test prevention strategies, yet, at present, there are no reports of a repeated limiting dose cochallenge model in which to evaluate products targeting HIV and HSV-2. Herein, we show that 20 weekly cochallenges with 2-50 TCID50 simian human immunodeficiency virus reverse transcriptase (SHIV-RT) and 10(7) pfu HSV-2 results in infection with both viruses (4/6 SHIV-RT, 6/6 HSV-2). The frequency and level of vaginal HSV-2 shedding were significantly greater in the repeated exposure model compared to the single high-dose model (p<0.0001). We used this new model to test the Council's on-demand microbicide gel, MZC, which is active against SHIV-RT in DP-treated macaques and HSV-2 and human papillomavirus (HPV) in mice. While MZC reduced SHIV and HSV-2 infections in our repeated limiting dose model when cochallenging 8?h after each gel application, a barrier effect of carrageenan (CG) that was not seen in DP-treated animals precluded evaluation of the significance of the antiviral activity of MZC. Both MZC and CG significantly (p<0.0001) reduced the frequency and level of vaginal HSV-2 shedding compared to no gel treatment. This validates the use of this repeated limiting dose cochallenge model for testing products targeting HIV and HSV-2.
机译:流行病学研究表明,流行的2型单纯疱疹病毒(HSV-2)感染增加了HIV感染的风险,强调需要开发共感染模型以评估有希望的预防策略。我们先前建立了经Depo-Provera(DP)处理的猕猴的猿猴人类免疫缺陷病毒(SHIV)/ HSV-2的单个高剂量阴道共感染模型。但是,此模型不能适当地模仿女性的暴露情况。重复限制剂量SHIV攻击模型现在已常规用于测试预防策略,但是,目前,尚无重复限制剂量挑战模型用于评估针对HIV和HSV-2的产品的报道。在这里,我们显示了每周2至50 TCID50猿人免疫缺陷病毒逆转录酶(SHIV-RT)和10(7)pfu HSV-2的挑战会同时感染两种病毒(4/6 SHIV-RT,6/6 HSV-2)。与单次高剂量模型相比,重复暴露模型中阴道HSV-2脱落的频率和水平明显更高(p <0.0001)。我们使用此新模型测试了市议会的按需杀微生物剂凝胶MZC,该凝胶对DP处理的猕猴和小鼠的HSV-2和人乳头瘤病毒(HPV)中的SHIV-RT具有活性。在我们每次重复施胶8小时后,在我们重复的限制性剂量模型中,MZC减少了SHIV和HSV-2感染,但角叉菜胶(CG)的阻隔作用在DP处理的动物中未见,因此无法评估抗病毒药的重要性MZC的活动。与未进行凝胶治疗相比,MZC和CG均显着(p <0.0001)降低了阴道HSV-2脱落的频率和水平。这验证了这种重复的限制性剂量挑战模型用于测试针对HIV和HSV-2的产品的用途。

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