Viral and immunological factors associated with breast milk transmission of SIV in rhesus macaques.
Viral and immunological factors associated with breast milk transmission of SIV in rhesus macaques.
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DOI：
10.1186/1742-4690-1-17
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发表时间：
2004-07-14
期刊：
影响因子：
3.3
通讯作者：
Ratterree M
中科院分区：
文献类型：
--
作者：
Amedee AM;Rychert J;Lacour N;Fresh L;Ratterree M
通过母乳喂养传播艾滋病毒所涉及的病毒和宿主因素在很大程度上是未知的，迫切需要采取干预战略来保护高危人群。为了评估与病毒乳汁传播直接相关的病毒和免疫因素，我们评估了哺乳期恒河猴（Macaca mulatta）作为HIV自然乳汁传播模型的猴免疫缺陷病毒（SIV）病程。14哺乳期猕猴静脉感染SIV/DeltaB 670，SIV的致病分离株，并在整个病程中与哺乳期婴儿成对饲养。在一年的时间里，观察到10对母婴传播。两名母亲在接种后14-21天的初始病毒血症期间传播了病毒被归类为早期的传播者早期递质的乳汁和血浆中的峰值病毒载量与其他动物相似，然而，早期递质随后显示出快速进展表型，并且在感染后56天未能控制病毒表达以及其他动物。8名母亲被归类为晚期传播者，在母亲SIV病程的慢性阶段（81至360天）的时间点检测到婴儿感染。血浆病毒载量，CD 4 + T细胞计数和SIV特异性抗体滴度在晚期发射器和非发射器中相似。然而，晚期母乳传播与较高的平均乳汁病毒载量和感染后12至46周乳汁中更持久的病毒表达相关。与非发射机相比。四位母亲没有传播病毒，尽管疾病进展和连续哺乳。这些研究验证了SIV感染恒河猴作为母乳传播HIV的模型。正如对感染艾滋病毒的妇女的研究所观察到的那样，传播发生在整个哺乳期的各个时间点。SIV感染慢性期的传播与病毒表达的阈值水平以及乳汁中更持久的脱落相关。这一模型将是一个宝贵的资源，破译病毒和宿主因素负责通过母乳喂养传播艾滋病毒。
The viral and host factors involved in transmission of HIV through breastfeeding are largely unknown, and intervention strategies are urgently needed to protect at-risk populations. To evaluate the viral and immunological factors directly related to milk transmission of virus, we have evaluated the disease course of Simian Immunodeficiency Virus (SIV) in lactating rhesus macaques (Macaca mulatta) as a model of natural breast milk transmission of HIV. Fourteen lactating macaques were infected intravenously with SIV/DeltaB670, a pathogenic isolate of SIV and were pair-housed with their suckling infants throughout the disease course. Transmission was observed in 10 mother-infant pairs over a one-year period. Two mothers transmitted virus during the period of initial viremia 14–21 days post inoculation (p.i.) and were classified as early transmitters. Peak viral loads in milk and plasma of early transmitters were similar to other animals, however the early transmitters subsequently displayed a rapid progressor phenotype and failed to control virus expression as well as other animals at 56 days p.i. Eight mothers were classified as late transmitters, with infant infection detected at time points in the chronic stage of the maternal SIV disease course (81 to 360 days). Plasma viral loads, CD4+ T cell counts and SIV-specific antibody titers were similar in late transmitters and non-transmitters. Late breast milk transmission, however, was correlated with higher average milk viral loads and more persistent viral expression in milk 12 to 46 weeks p.i. as compared to non-transmitters. Four mothers failed to transmit virus, despite disease progression and continuous lactation. These studies validate the SIV-infected rhesus macaque as a model for breast milk transmission of HIV. As observed in studies of HIV-infected women, transmission occurred at time points throughout the period of lactation. Transmission during the chronic stage of SIV-infection correlated with a threshold level of virus expression as well as more persistent shedding in milk. This model will be a valuable resource for deciphering viral and host factors responsible for transmission of HIV through breastfeeding.