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）：本申请是对题为“抑制 HIV 和机会性感染的口腔粘膜先天免疫因子”的 NIH RFA (DE-03-002) 的回应。具体来说，我们将研究共生细菌的口腔先天免疫的新因子——甘露糖结合凝集素（MBL）。 其基本原理是，人类 MBL 可以结合并中和 HIV，但它仅存在于血清中，而不存在于大多数 HIV 感染发生的粘膜表面。我们认为，粘膜表面宿主 MBL 的缺乏可以通过共生细菌的 MBL 样凝集素来补偿，至少部分补偿。我们的初步研究表明，一些定植于口腔的乳酸杆菌会产生中等水平的 MBL 样凝集素。与人类 MBL 一样，微生物 MBL 样凝集素也能结合 HIV，因为 HIV 受体 gpl20 富含甘露糖残基。乳杆菌自然生长在牛奶中（lacto=牛奶），是牛奶喂养婴儿口腔和肠粘膜最早的定殖者，也是婴儿针对腹泻等传染病的先天免疫力的起始组成部分。然而，微生物 MBL 样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丰富的 MBL 样凝集素、对 HIV 具有高亲和力的口腔乳杆菌。我们将通过追求两个特定目标来获得这些超级 MBL 乳酸杆菌： 1)通过筛选自发发生和/或诱导的突变体获得super-MBL乳杆菌菌株。 2）测试super-MBL乳酸杆菌体外阻断HIV病毒的能力 这项研究完成后，我们将获得一组能够高效结合和中和 HIV 的 super-MBL 口腔乳酸杆菌。这些细菌将用于进一步研究其结合特性、安全性、体内功效以及在动物和最终人类志愿者中的定植。该项目的长期目标是选择能够自然捕获和杀死艾滋病毒病毒的食品级共生细菌，并开发一种生物预防疗法，以安全地阻止艾滋病毒通过母乳喂养的垂直传播。