近日,,來自北卡羅來納大學(xué)的HIV研究者提出了一個問題:在哺乳的過程中,母乳是起到了一個傳輸病毒的作用呢,?還是保護(hù)防御病毒的作用呢,?針對此問題,研究者在小鼠模型中進(jìn)行了相關(guān)研究,,研究揭示了母乳有一個較強(qiáng)的病毒殺滅效應(yīng),,并且可以保護(hù)嬰兒免于病毒感染,。這項研究成果為我們理解母乳有效破壞HIV病毒提供了新視野,科學(xué)家也可以從母乳中分離出有效物質(zhì)來殺滅病毒,。
研究者Garcia和其同事構(gòu)建了人化的BLT小鼠模型,,這種小鼠模型通過引入人類的骨髓,、肝臟和胸腺組織來構(gòu)建而成,。(無免疫系統(tǒng));BLT小鼠有完全分化為人尅免疫系統(tǒng)的功能,,而且可以被HIV感染(與HIV感染人類的方式相同),。
這項研究中,研究者揭示了小鼠的口腔和上消化道有和人類相同的細(xì)胞,,其可以影響HIV的口腔轉(zhuǎn)移能力,,這就保證了小鼠可以和人類有同樣的方式來進(jìn)行HIV的感染。隨后研究者通過在HIV陰性母親的母乳中加入HIV,,通過感染小鼠,,發(fā)現(xiàn)HIV可以在小鼠中成功轉(zhuǎn)移。研究者發(fā)現(xiàn)母乳可以完全阻止HIV以任何形式在口腔中進(jìn)行轉(zhuǎn)移傳遞,,這就反駁了原先的假設(shè),,認(rèn)為細(xì)胞中的HIV病毒相比HIV病毒顆粒更能抵御機(jī)體先天的免疫防御系統(tǒng)。
最終研究者研究了抗HIV治療的前預(yù)防法(PrEP)的有效性,。Garcia以前的研究揭示了在BLT小鼠中PrEP可以有效抵御靜脈,、直腸的HIV傳染轉(zhuǎn)移。這項最新研究中研究者連續(xù)給予小鼠反轉(zhuǎn)錄病毒藥物7天,,結(jié)果顯示小鼠可以100%抵御病毒的轉(zhuǎn)移和傳遞,。
研究者的這項最新研究為我們開發(fā)新的治療方法提供了線索,相關(guān)研究成果刊登在了國際著名雜志PLoS Pathogens上,。(生物谷Bioon.com)
編譯自:Breast Milk Kills HIV and Blocks Its Oral Transmission in Humanized Mouse
編譯者:天使托
doi:10.1371/journal.ppat.1002732
PMC:
PMID:
Human Breast Milk and Antiretrovirals Dramatically Reduce Oral HIV-1 Transmission in BLT Humanized Mice
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.