Carthagena Laetitia, Becquart Pierre, Hocini Hakim, Kazatchkine Michel D, Bouhlal Hicham, Belec Laurent
Inserm U743/Team « Immunité et Biothérapie Muqueuse », Paris, France.
Open Virol J. 2011;5:27-34. doi: 10.2174/1874357901105010027. Epub 2011 Apr 15.
Lactoferrin (LF), a multifunctional molecule present in human secretions, has potent inhibitory activities against human immunodeficiency virus (HIV). The aim of the study was to evaluate whether human LF (hLF) and its exposed domain LF-33 represented by the peptide (LF-33-GRRRRSVQWCAVSQPEATKCFQWQRNMRKVRGP) involved in LF-HIV gag binding and endotoxines neutralization, may inhibit early steps of HIV mucosal transmission. Human LF and the peptide LF-33 inhibited the attachment of primary X4-tropic HIV-1(NDK) and R5-tropic HIV-1(JR-CSF) strains to human endometrial (HEC-1) and colorectal (HT-29) CD4-negative epithelial cells, the purified hLF being more potent (up to 80%) than the LF-33 peptide. In addition, the hLF, but not the LF-33 peptide, inhibited up to 40% the transfer in trans of HIV-1(JR-CSF) and HIV-1(NDK,) from immature dendritic cells to CD4 T lymphocytes, likely in a DC-SIGN-dependent manner. Altogether, these findings demonstrate that hLF can interfere with HIV-1 mucosal transmission by blocking virus attachment to epithelial cells and by inhibiting virus transfer from dendritic cells to CD4 T cells, two crucial steps of HIV dissemination from mucosae to lymphoid tissue.
乳铁蛋白（LF）是一种存在于人体分泌物中的多功能分子，对人类免疫缺陷病毒（HIV）具有强大的抑制活性。本研究的目的是评估人乳铁蛋白（hLF）及其由参与LF-HIV gag结合和内毒素中和的肽（LF-33-GRRRRSVQWCAVSQPEATKCFQWQRNMRKVRGP）所代表的暴露结构域LF-33是否可能抑制HIV黏膜传播的早期步骤。人乳铁蛋白和肽LF-33抑制了原发性X4嗜性HIV-1（NDK）和R5嗜性HIV-1（JR-CSF）毒株与人子宫内膜（HEC-1）和结肠直肠（HT-29）CD4阴性上皮细胞的附着，纯化的hLF比LF-33肽更有效（高达80%）。此外，hLF而非LF-33肽以可能依赖于DC-SIGN的方式抑制了高达40%的HIV-1（JR-CSF）和HIV-1（NDK）从未成熟树突状细胞向CD4 T淋巴细胞的跨膜转移。总之，这些发现表明hLF可通过阻断病毒与上皮细胞的附着以及抑制病毒从未成熟树突状细胞向CD4 T细胞的转移来干扰HIV-1的黏膜传播，这是HIV从黏膜向淋巴组织传播的两个关键步骤。
