Pathogenic Consequences of Vaginal Infection with CCR5-Tropic Simian-Human Immunodeficiency Virus SHIVSF162P3N
Pathogenic Consequences of Vaginal Infection with CCR5-Tropic Simian-Human Immunodeficiency Virus SHIVSF162P3N
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DOI：
10.1128/jvi.00852-12
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发表时间：
2012-09-01
影响因子：
5.4
通讯作者：
Cheng-Mayer, Cecilia
中科院分区：
文献类型：
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作者：
Shakirzyanova, Madina;Tsai, Lily;Cheng-Mayer, Cecilia
我们先前报道了通过静脉内和直肠内接种在印度恒河猴中有效传播致病性R5猿-人免疫缺陷病毒SHIVSF 162 P3 N分离株，在50%的感染动物中转换为CXCR 4辅助受体使用，并迅速进展为疾病。由于妇女继续受到不成比例的艾滋病毒的影响，我们开发了一种动物模型的基础上阴道内的挑战，雌性恒河猴与SHIVSF 162 P3 N，并试图验证该模型的效用，研究艾滋病毒的传播和发病机制的相关方面。评价病毒剂量对感染结果的影响，以确定评价HIV-1预防和治疗策略的最佳条件。我们发现，病毒可以成功地穿过阴道粘膜表面建立感染，并通过辅助受体转换诱导疾病，但与静脉内和直肠传播相比，效率较低。相反，直肠内感染，峰值和累积病毒载量超过1年的感染期显着更大的猕猴暴露在阴道内较低，而不是较高的接种剂量。此外，仅在同一天内用高剂量病毒阴道内攻毒两次的猕猴中观察到低水平和一过性病毒血症，可视为剂量加倍。综上所述，这些结果表明SHIVSF 162 P3 N可以成功地通过生殖器粘膜传递，进行辅助受体转换，并诱导疾病。然而，施用的剂量似乎以意想不到的方式影响SHIVSF 162 P3 N阴道感染结果。
We previously reported efficient transmission of the pathogenic R5 simian-human immunodeficiency virus SHIVSF162P3N isolate in Indian rhesus macaques by intravenous and intrarectal inoculations, with a switch to CXCR4 coreceptor usage in similar to 50% of infected animals that progressed rapidly to disease. Since women continue to be disproportionately affected by HIV, we developed an animal model based on the intravaginal challenge of female rhesus monkeys with SHIVSF162P3N and sought to validate the utility of this model to study relevant aspects of HIV transmission and pathogenesis. The effect of viral dose on infection outcome was evaluated to determine the optimal conditions for the evaluation of HIV-1 preventive and therapeutic strategies. We found that the virus can successfully cross the vaginal mucosal surface to establish infection and induce disease with coreceptor switch, but with lower efficiencies compared to intravenous and rectal transmissions. In contrast to intrarectal infection, peak and cumulative viral load over a 1 year-infection period were significantly greater in macaques exposed intravaginally to lower rather than higher inoculum doses. Moreover, low and transient viremia was observed only in macaques that were challenged intravaginally twice within the same day with a high dose of virus, which can be seen as doubling the dose. Taken together, these results show that SHIVSF162P3N can successfully transmit across the genital mucosa, undergo coreceptor switch, and induce disease. However, the administered dose appears to impact SHIVSF162P3N vaginal infection outcome in an unexpected manner.