PAUCITY OF CD4+CCR5+ T CELLS AND BREASTFEEDING SIV TRANSMISSION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 背景：猴免疫缺陷病毒(SIV)在非洲非人灵长类野生种群中的持续存在可能通过水平和垂直传播发生。然而，后一种传播的机制(S)和传播时间迄今尚未调查。在这里，我们提出了第一个关于SIV在非洲NHP宿主中通过母乳喂养的传播性的研究。 方法：用含300~50%组织培养感染量的SIVmND-1的血浆于产后第2天感染6只黄鼠。正如血浆病毒载量(VLS)和抗SIVmND-1血清转换所证明的那样，所有的雌性沙鼠都被感染了。 结果与讨论：无发热，无淋巴结肿大。在SIVmND-1病毒复制高峰期(接种后7~10天)，血浆VLS含量较高(8×10~8个RNA拷贝/ml)，与牛奶中的VLS(4.7×10~4~5.6±105RNA/ml)相当。然而，在母乳喂养期结束时，经过6个月的随访，没有观察到后代感染的迹象。后来，在为期4年的跟踪检查中，其中两个后代显示出SIVmand-1感染的病毒学证据。两只动物在中断哺乳后至少6个月血清转换。总而言之，尽管沙鼠妈妈的病毒大量复制，牛奶中的游离病毒水平很高，但在母乳喂养时或在接下来的几个月中，没有检测到SIVmND-1传播。由于我们观察到幼年山竹和非洲绿猴的CD4+T细胞上CCR5的表达明显低于成人，我们推测这种在CD4+T细胞上的低水平的病毒辅助受体可能与SIV自然宿主缺乏母乳喂养传播有关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: Simian immunodeficiency virus (SIV) persistence in wild populations of African nonhuman primates (NHPs) may occur through horizontal and vertical transmission. However, the mechanism(s) and timing of the latter type of transmission have not been investigated to date. Here we present the first study of SIV transmissibility by breast-feeding in an African NHP host. Methods: Six mandrill dames were infected with plasma containing 300 50% tissue culture infective doses of SIVmnd-1 on the day after delivery. All female mandrills became infected, as demonstrated by both plasma viral loads (VLs) and anti-SIVmnd-1 seroconversion. Results and Dicussion: Neither fever nor lymphadenopathy was observed. At the peak of SIVmnd-1 viral replication (days 7 to 10 postinoculation), plasma VLs were high (8 ¿ 10^6 to 8 ¿ 10^8 RNA copies/ml) and paralleled the high VLs in milk (4.7 ¿ 10^4 to 5.6 ¿ 105 RNA/ml). However, at the end of the breast-feeding period, after 6 months of follow-up, no sign of infection was observed for the offspring. Later on, during a 4-year follow-up examination, two of the offspring showed virological evidence of SIVmnd-1 infection. Both animals seroconverted at least 6 months after the interruption of lactation. In conclusion, despite extensive viral replication in mandrill mothers and high levels of free virus in milk, no SIVmnd-1 transmission was detectable at the time of breast-feeding or during the following months. Since we observed a markedly lower expression of CCR5 on the CD4+ T cells of young mandrills and African green monkeys than on those of adults, we propose that low levels of this viral coreceptor on CD4+ T cells may be involved in the lack of breast-feeding transmission in natural hosts of SIVs.