Relative Transmissibility of an R5 Clade C Simian-Human Immunodeficiency Virus Across Different Mucosae in Macaques Parallels the Relative Risks of Sexual HIV-1 Transmission in Humans via Different Routes
Relative Transmissibility of an R5 Clade C Simian-Human Immunodeficiency Virus Across Different Mucosae in Macaques Parallels the Relative Risks of Sexual HIV-1 Transmission in Humans via Different Routes
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DOI：
10.1086/651274
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发表时间：
2010-04-15
影响因子：
6.4
通讯作者：
Ruprecht, Ruth M.
中科院分区：
文献类型：
--
作者：
Chenine, Agnes L.;Siddappa, Nagadenahalli B.;Ruprecht, Ruth M.
背景。在世界范围内，大约90%的人类免疫缺陷病毒（HIV）传播发生在粘膜上；几乎都涉及R5菌株。性感染HIV的风险最高的是直肠接触，其次是阴道接触，最后是口腔接触。粘膜撕裂可能影响对HIV易感性的等级顺序，但不能在人类中进行评估。我们使用SHIV-1157ipd3N4（一种编码原发R5 HIV分支C env (SHIV-C)）的猿人免疫缺陷病毒)的单个stock，测量了病毒在猕猴完整粘膜中的相对传播性。恒河猴粘膜的穿透性差异显著，直肠攻击所需病毒最少，其次是阴道和口腔途径（P = 0.31，口腔vs阴道；P < 0.001直肠vs阴道）。这些发现表明，粘膜的内在性质是造成粘膜通透性差异的原因。后者与人类报告的等级顺序相似，相对风险估计在人类流行病学研究范围内。为了测试炎症是否促进病毒传播——正如从人类研究中预测的那样——我们建立了一个局部口腔炎症的猕猴模型。全身性感染发生在发炎而非正常的口腔黏膜。我们的灵长类动物数据概括了在人类中观察到的病毒传播风险，从而在猕猴中建立了R5 SHIV-1157ipd3N4作为一个强大的模型系统来研究参与人类粘膜HIV传播及其预防的辅助因子。
Background. Worldwide, similar to 90% of all human immunodeficiency virus (HIV) transmissions occur mucosally; almost all involve R5 strains. Risks of sexual HIV acquisition are highest for rectal, then vaginal, and finally oral exposures.Methods. Mucosal lacerations may affect the rank order of susceptibility to HIV but cannot be assessed in humans. We measured relative virus transmissibility across intact mucosae in macaques using a single stock of SHIV-1157ipd3N4, a simian-human immunodeficiency virus encoding a primary R5 HIV clade C env (SHIV-C).Results. The penetrability of rhesus macaque mucosae differed significantly, with rectal challenge requiring the least virus, followed by vaginal and then oral routes (P = 0.31, oral vs vaginal; P < .001 rectal vs vaginal). These findings imply that intrinsic mucosal properties are responsible for the differential mucosal permeability. The latter paralleled the rank order reported for humans, with relative risk estimates within the range of epidemiological human studies. To test whether inflammation facilitates virus transmission - as predicted from human studies we established a macaque model of localized buccal inflammation. Systemic infection occurred across inflamed but not normal buccal mucosa.Conclusion. Our primate data recapitulate virus transmission risks observed in humans, thus establishing R5 SHIV-1157ipd3N4 in macaques as a robust model system to study cofactors involved in human mucosal HIV transmission and its prevention.