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

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 背景资料：猴免疫缺陷病毒（SIV）在非洲非人灵长类动物（NHP）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，迄今尚未对后一种传播的机制和时间进行调查。在这里，我们提出了第一个研究SIV通过母乳喂养在非洲NHP主机的传播。 方法：6只雌性山鸡于分娩后第2天用含300 - 50%组织培养感染剂量SIVmnd-1的血浆感染。所有雌性山鸡都被感染，如血浆病毒载量（VL）和抗SIVmnd-1血清转化所示。 结果和描述：没有观察到发热和淋巴结肿大。在SIVmnd-1病毒复制的高峰期（接种后第7至10天），血浆VL较高（8 <$10^6至8 <$10^8 RNA拷贝/ml），并高于乳汁中的高VL（4.7 <$10^4至5.6 <$10^5 RNA/ml）。然而，在母乳喂养期结束时，经过6个月的随访，未观察到后代感染的迹象。后来，在4年的随访检查中，其中两个后代显示出SIVmnd-1感染的病毒学证据。这两只动物在泌乳中断后至少6个月发生血清转化。总之，尽管在大山雀母亲中广泛的病毒复制和乳汁中高水平的游离病毒，但在母乳喂养时或随后的几个月内没有检测到SIVmnd-1传播。由于我们观察到一个显着较低的表达CCR 5的CD 4 + T细胞的年轻的山海关和非洲绿色猴比成年人，我们建议，低水平的这种病毒辅助受体的CD 4 + T细胞可能参与缺乏母乳喂养的传播在自然宿主的SIV。

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.