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黏液和黏蛋白:它们在抑制人类免疫缺陷病毒中发挥作用吗?

Mucus and Mucins: do they have a role in the inhibition of the human immunodeficiency virus?

机构信息

Division of General Surgery, University of Cape Town and Immune Modulation and Biotherapeutics Discovery, Boehringer- Ingelheim, Danbury, USA.

Discipline of Medical Virology, University of Stellenbosch & Tygerberg Hospital, Parow, South Africa.

出版信息

Virol J. 2017 Oct 6;14(1):192. doi: 10.1186/s12985-017-0855-9.

Abstract

BACKGROUND

Mucins are large O-linked glycosylated proteins which give mucus their gel-forming properties. There are indications that mucus and mucins in saliva, breast milk and in the cervical plug inhibit the human immunodeficiency virus (HIV-1) in an in vitro assay. Crude mucus gels form continuous layers on the epithelial surfaces of the major internal tracts of the body and protect these epithelial surfaces against aggressive luminal factors such as hydrochloric acid and pepsin proteolysis in the stomach lumen, the movement of hard faecal pellets in the colon at high pressure, the effects of shear against the vaginal epithelium during intercourse and the presence of foreign substances in the respiratory airways. Tumour-associated epitopes on mucins make them suitable as immune-targets on malignant epithelial cells, rendering mucins important as diagnostic and prognostic markers for various diseases, even influencing the design of mucin-based vaccines. Sub-Saharan Africa has the highest prevalence of HIV-AIDS in the world. The main points of viral transmission are via the vaginal epithelium during sexual intercourse and mother-to-child transmission during breast-feeding. There have been many studies showing that several body fluids have components that prevent the transmission of HIV-1 from infected to non-infected persons through various forms of contact. Crude saliva and its purified mucins, MUC5B and MUC7, and the purified mucins from breast milk, MUC1 and MUC4 and pregnancy plug cervical mucus (MUC2, MUC5AC, MUC5B and MUC6), inhibit HIV-1 in an in vitro assay. There are conflicting reports of whether crude breast-milk inhibits HIV-1 in an in vitro assay. However studies with a humanised BLT mouse show that breast-milk does inhibit HIV and that breast-feeding is still advisable even amongst HIV-positive women in under-resourced areas, preferably in conjunction with anti-retroviral treatment.

CONCLUSION

These findings raise questions of how such a naturally occurring biological substance such as mucus, with remarkable protective properties of epithelial surfaces against aggressive luminal factors in delicate locations, could be used as a tool in the fight against HIV-AIDS, which has reached epidemic proportions in sub-Saharan Africa.

摘要

背景

粘蛋白是一种大型 O 连接糖基化蛋白,使粘液具有凝胶形成特性。有迹象表明,唾液、母乳和宫颈栓中的粘液和粘蛋白在体外试验中抑制人类免疫缺陷病毒 (HIV-1)。粗制粘液凝胶在身体主要内部通道的上皮表面形成连续层,保护这些上皮表面免受胃腔中盐酸和胃蛋白酶消化、结肠高压下硬粪便颗粒运动、性交时对阴道上皮的剪切作用以及呼吸道中异物等侵袭性腔道因素的侵害。粘蛋白上的肿瘤相关表位使它们成为恶性上皮细胞的免疫靶标,使粘蛋白成为各种疾病的重要诊断和预后标志物,甚至影响基于粘蛋白的疫苗的设计。撒哈拉以南非洲地区是世界上 HIV/AIDS 发病率最高的地区。病毒传播的主要途径是通过阴道上皮在性交期间和母乳喂养期间从母亲传播给婴儿。有许多研究表明,几种体液中的成分可通过各种形式的接触阻止 HIV-1 从受感染个体传播给未感染个体。粗唾液及其纯化粘蛋白 MUC5B 和 MUC7 以及母乳中的纯化粘蛋白 MUC1 和 MUC4 和妊娠栓宫颈粘液 (MUC2、MUC5AC、MUC5B 和 MUC6) 在体外试验中抑制 HIV-1。有关于粗制母乳是否在体外试验中抑制 HIV-1 的相互矛盾的报告。然而,在人源化 BLT 小鼠中的研究表明,母乳确实抑制 HIV,并且即使在资源匮乏地区的 HIV 阳性妇女中,母乳喂养仍然是可取的,最好与抗逆转录病毒治疗相结合。

结论

这些发现提出了这样一个问题,即如此自然存在的生物物质,如粘液,具有在微妙部位保护上皮表面免受侵袭性腔道因素侵害的显著保护特性,如何能作为抗击 HIV-AIDS 的工具,该疾病在撒哈拉以南非洲已达到流行程度。

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