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PLoS Pathog:研究揭示母乳或可有效杀灭HIV

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<p align="center"><span style="font-family: 楷体_GB2312; font-size: x-small;">研究者揭示母乳存在一个较强的病毒杀灭效应。</span></p>
<p align="center"><span style="font-family: 楷体_GB2312; font-size: x-small;">(Credit: University of North Carolina School of Medicine)</span></p>
近日,来自北卡罗来纳大学的HIV研究者提出了一个问题:在哺乳的过程中,母乳是起到了一个传输病毒的作用呢?还是保护防御病毒的作用呢?针对此问题,研究者在小鼠模型中进行了相关研究,研究揭示了母乳有一个较强的病毒杀灭效应,并且可以保护婴儿免于病毒感染。这项研究成果为我们理解母乳有效破坏HIV病毒提供了新视野,科学家也可以从母乳中分离出有效物质来杀灭病毒。

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研究者Garcia和其同事构建了人化的BLT小鼠模型,这种小鼠模型通过引入人类的骨髓、肝脏和胸腺组织来构建而成。(无免疫系统);BLT小鼠有完全分化为人尅免疫系统的功能,而且可以被HIV感染(与HIV感染人类的方式相同)。

这项研究中,研究者揭示了小鼠的口腔和上消化道有和人类相同的细胞,其可以影响HIV的口腔转移能力,这就保证了小鼠可以和人类有同样的方式来进行HIV的感染。随后研究者通过在HIV阴性母亲的母乳中加入HIV,通过感染小鼠,发现HIV可以在小鼠中成功转移。研究者发现母乳可以完全阻止HIV以任何形式在口腔中进行转移传递,这就反驳了原先的假设,认为细胞中的HIV病毒相比HIV病毒颗粒更能抵御机体先天的免疫防御系统。

最终研究者研究了抗HIV治疗的前预防法(PrEP)的有效性。Garcia以前的研究揭示了在BLT小鼠中PrEP可以有效抵御静脉、直肠的HIV传染转移。这项最新研究中研究者连续给予小鼠反转录病毒药物7天,结果显示小鼠可以100%抵御病毒的转移和传递。

研究者的这项最新研究为我们开发新的治疗方法提供了线索,相关研究成果刊登在了国际著名杂志<em>PLoS Pathogens</em>上。

编译自:<a title="" href="http://www.sciencedaily.com/releases/2012/06/120614182751.htm" target="_blank">Breast Milk Kills HIV and Blocks Its Oral Transmission in Humanized Mouse</a>
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<a title="" href="http://dx.doi.org/doi:10.1371/journal.ppat.1002732" target="_blank">doi:10.1371/journal.ppat.1002732</a>
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<br/><strong>Human Breast Milk and Antiretrovirals Dramatically Reduce Oral HIV-1 Transmission in BLT Humanized Mice</strong><br/>


Angela Wahl1, Michael D. Swanson1, Tomonori Nochi1, Rikke Olesen1,2, Paul W. Denton1, Morgan Chateau1, J. Victor Garcia1*

Currently, over 15% of new HIV infections occur in children. Breastfeeding is a major contributor to HIV infections in infants. This represents a major paradox in the field because in vitro, breast milk has been shown to have a strong inhibitory effect on HIV infectivity. However, this inhibitory effect has never been demonstrated in vivo. Here, we address this important paradox using the first humanized mouse model of oral HIV transmission. We established that reconstitution of the oral cavity and upper gastrointestinal (GI) tract of humanized bone marrow/liver/thymus (BLT) mice with human leukocytes, including the human cell types important for mucosal HIV transmission (i.e. dendritic cells, macrophages and CD4+ T cells), renders them susceptible to oral transmission of cell-free and cell-associated HIV. Oral transmission of HIV resulted in systemic infection of lymphoid and non-lymphoid tissues that is characterized by the presence of HIV RNA in plasma and a gradual decline of CD4+ T cells in peripheral blood. Consistent with infection of the oral cavity, we observed virus shedding into saliva. We then evaluated the role of human breast milk on oral HIV transmission. Our in vivo results demonstrate that breast milk has a strong inhibitory effect on oral transmission of both cell-free and cell-associated HIV. Finally, we evaluated the effect of antiretrovirals on oral transmission of HIV. Our results show that systemic antiretrovirals administered prior to exposure can efficiently prevent oral HIV transmission in BLT mice.

<br/>来源:生物谷

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