HIV-1 infection of human penile explant tissue and protection by candidate microbicides.
HIV-1 infection of human penile explant tissue and protection by candidate microbicides.
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DOI：
10.1097/qad.0b013e328321b778
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发表时间：
2009-01-28
期刊：
影响因子：
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通讯作者：
Shattock RJ
中科院分区：
文献类型：
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作者：
Fischetti L;Barry SM;Hope TJ;Shattock RJ
男性生殖器粘膜表面暴露与感染建立之间的控制因素尚不清楚。此外，人们对杀菌剂对男性生殖器粘膜的安全性和有效性知之甚少。在这里，我们提出了一种新型阴茎组织外植体模型，用于表征男性生殖器组织的 HIV-1 感染机制并评估候选杀菌剂。确定从性别重置和包皮环切获得的龟头、尿道和包皮的粘膜外植体培养条件。通过显微镜观察 CD4+ 和 CD1a+ 细胞的密度和分布。通过测量 p24 的释放来确定体外 HIV-1 感染，同时通过测量组织活力、细胞因子表达和 p24 的产生来评估杀菌剂的生物相容性和功效。培养的龟头和包皮显示出相当的上皮厚度，但 CD4+ 和 CD1a+ 细胞密度存在一些差异。所有检查的组织部位（包皮、龟头、尿道口）都同样容易受到 R5 HIV-1 感染，这种感染通过从组织中迁移出来的迁移细胞进行有效传播。相比之下，X4 HIV-1 无法感染粘膜组织，并且迁移细胞的传播效率较低。三种候选杀菌剂 PMPA、PRO 2000 和 Cyanovirin-N 显示出良好的组织相容性并能有效预防 HIV-1 感染，仅引起组织细胞因子谱的微小变化。所描述的模型为研究男性生殖组织HIV-1感染的决定因素提供了一个有用的模型，并且可能成为未来开发候选杀菌剂和概念的重要工具。
Factors governing events between exposure of male genital mucosa surfaces and the establishment of infection are poorly understood. Furthermore, little is known about the safety and efficacy of microbicides on male genital mucosa. Here we present a novel penile tissue explant model to characterise the mechanisms of HIV-1 infection of male genital tissue and evaluate candidate microbicides. Mucosal explant culture conditions were determined for glans, urethra and foreskin obtained from gender reassignment and circumcision. Density and distribution of CD4+ and CD1a+ cells were visualized by microscopy. In vitro HIV-1 infection was determined by measuring p24 release, while microbicide biocompatibility and efficacy were assessed by measurement of tissue viability, cytokine expression and p24 production. Cultured glans and foreskin showed comparable epithelial thickness but some differences in CD4+ and CD1a+ cell density. All tissue sites examined (foreskin, glans, meatus, urethra) were equally susceptible to R5 HIV-1 infection, which was productively disseminated by migratory cells emigrating from tissue. In contrast, X4 HIV-1 failed to infect mucosal tissue and dissemination by migratory cells was less efficient. The three candidate microbicides PMPA, PRO 2000 and Cyanovirin-N, showed good tissue compatibility and efficient prevention of HIV-1 infection, causing only minor changes in tissue cytokine profile. The described model provides a useful model to study the determinants of HIV-1 infection of male genital tissue and is likely to be an important tool for the future development of microbicide candidates and concepts.