Blocking Milk-Borne HIV by Commensal Bacteria

通过共生细菌阻断乳源性艾滋病毒

• 批准号: 6772447
• 负责人: LIN TAO
• 金额: $ 23.38万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-10 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6772447
• 关键词: AIDS education /prevention; HIV envelope protein gp120; HIV infections; HeLa cells; Lactobacillus; breast feeding; human immunodeficiency virus 1; lectin; mannose; methane sulfonate; mutant; symbiosis; tissue /cell culture; tissue /cell preparation; vertical transmission

DESCRIPTION (provided by applicant): This application is in response to the NIH RFA (DE-03-002) entitled "Oral Mucosal Innate Immune Factors in the Inhibition of HIV and Opportunistic Infections." Specifically, we will study a novel factor of the oral innate immunity--mannose-binding lectin (MBL)--of commensal bacteria. The rationale is that the human MBL binds and neutralizes HIV, but it exists only in serum, not on mucosal surfaces where most HIV infections occur. We think that the lack of host MBL on mucosal surfaces can be compensated, at least in part, by MBL-like lectins of commensal bacteria. Our preliminary studies showed that some lactobacilli that colonize the oral cavity produce moderate levels of MBL-like lectin. Like the human MBL, microbial MBL-like lectins also bind HIV because the HIV receptor, gpl20, is rich in mannose-residues. Lactobacilli, which naturally grow in milk (lacto=milk), are earliest colonizers of the oral and intestinal mucosa in milk-fed infants and are a beginning component of the infant's innate immunity against infectious diseases, such as diarrhea. However, the affinity of microbial MBL-Iike lectins are not high enough to block HIV infections. We hypothesize that oral lactobacilli that produce abundant MBL-like lectins with a high affinity against HIV can be isolated from spontaneously occurred and/or induced mutants. We will obtain these super-MBL lactobacilli by pursuing two specific aims: 1) Obtain super-MBL Lactobacillus strains by screening spontaneously occurred and/or induced mutants. 2) Test the ability of super-MBL lactobacilli to block HIV viruses in vitro Upon completion of this study, we will have obtained a collection of super-MBL oral lactobacilli that bind and neutralize HIV with high efficiency. These bacteria will be used for further studies on their binding characteristics, safety, in vivo efficacy and colonization in animals and ultimately in human volunteers. The long-term goal of this project is to select food-grade commensal bacteria that naturally trap and kill HIV viruses and to develop a bioprophylactic therapy to safely block the vertical transmission of HIV via breastfeeding.

描述（由申请人提供）：此申请是对NIH RFA（DE-03-002）的响应，标题为“口服粘膜先天免疫因素在抑制HIV和机会性感染中”。具体而言，我们将研究共生细菌口服先天免疫 - 甘露结合凝集素（MBL）的新因素。 理由是人类MBL结合并中和HIV，但仅存在于血清中，而不存在于大多数HIV感染的粘膜表面上。我们认为，粘膜表面上缺乏宿主MBL，至少可以部分通过共生细菌的MBL样凝集素来补偿。我们的初步研究表明，某些定植口腔的乳杆菌会产生中等水平的MBL样凝集素。像人类MBL一样，微生物MBL样凝集素也会结合HIV，因为HIV受体GPL20富含甘露糖 - 分析。乳酸乳杆菌自然生长在牛奶中（乳糖=牛奶），是牛奶喂养婴儿中口腔和肠粘膜的最早殖民者，并且是婴儿对感染性疾病的先天免疫力的起点，例如腹泻。但是，微生物MBL-IKIK凝集素的亲和力不足以阻止HIV感染。我们假设可以从自发发生和/或诱导的突变体中分离出产生具有高亲和力的大量MBL样凝集素的口服乳酸杆菌。我们将通过追求两个具体目标来获得这些超级MBL乳酸杆菌： 1）通过自发发生和/或诱导的突变体筛选来获得超级MBL乳酸菌菌株。 2）测试超级MBL乳酸杆菌在体外阻断HIV病毒的能力 这项研究完成后，我们将获得一系列超级MBL口服乳酸杆菌的集合，该乳酸杆菌以高效率结合和中和HIV。这些细菌将用于进一步研究其结合特征，安全性，体内功效和动物的定殖，并最终在人类志愿者中。该项目的长期目标是选择自然捕获和杀死HIV病毒并开发生物预防疗法的食品级共生细菌，以通过母乳喂养安全地阻止HIV的垂直传播。