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关于使用百日咳毒素调节恒河猴阴道内猴免疫缺陷病毒传播的初步研究。

Preliminary studies on the use of pertussis toxin for the modulation of intravaginal SIV transmission in rhesus macaques.

作者信息

Ortiz Kristina, Sampathkumar Rebecca S, Ansari Aftab A, Byrareddy Siddappa N

机构信息

Department of Pathology & Lab Medicine, Emory University School of Medicine, Atlanta, GA, USA.

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.

出版信息

J Med Primatol. 2017 Dec;46(6):327-331. doi: 10.1111/jmp.12316. Epub 2017 Sep 21.

Abstract

BACKGROUND

Pertussis toxin (PTX) blocks GPCR signaling resulting in the inhibition of chemotaxis/cell adhesion. It was reasoned that inhibition of cell trafficking may be an approach to prevent HIV/SIV transmission.

METHODS

In this study, PTX in HEC gel was applied to the vaginal wall of monkeys that were then challenged intravaginally with SIVmac251.

RESULTS

Results of these studies showed that 2 of 4 animals were resistant to infection. Furthermore, infection was correlated with a marked increase in the plasma and cervicovaginal lavage levels of select chemokines and cytokines.

CONCLUSIONS

Results from this preliminary feasibility study dictate that further studies that include a larger number of animals are required to optimize this protocol and establish the efficacy of this approach. In addition, such future studies will provide important information on the role of specific chemokines that play a role in lymphocyte trafficking within the genital tract and serve as additional therapeutic targets.

摘要

背景

百日咳毒素(PTX)可阻断GPCR信号传导,从而抑制趋化性/细胞黏附。据推测,抑制细胞运输可能是预防HIV/SIV传播的一种方法。

方法

在本研究中,将含PTX的HEC凝胶应用于猴子的阴道壁,随后经阴道用SIVmac251进行攻击。

结果

这些研究结果显示,4只动物中有2只对感染具有抗性。此外,感染与特定趋化因子和细胞因子的血浆及宫颈阴道灌洗水平显著升高相关。

结论

这项初步可行性研究的结果表明,需要开展包括更多动物的进一步研究以优化该方案并确定此方法的疗效。此外,此类未来研究将提供有关特定趋化因子在生殖道内淋巴细胞运输中所起作用的重要信息,并作为额外的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/431a/5673538/47f78301d8d3/nihms903214f1.jpg

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