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针对1型人类免疫缺陷病毒的中和单克隆抗体不会抑制病毒通过黏膜上皮细胞的转胞吞作用。

Neutralizing monoclonal antibodies to human immunodeficiency virus type 1 do not inhibit viral transcytosis through mucosal epithelial cells.

作者信息

Chomont Nicolas, Hocini Hakim, Gody Jean-Chrysostome, Bouhlal Hicham, Becquart Pierre, Krief-Bouillet Corinne, Kazatchkine Michel, Bélec Laurent

机构信息

Université Paris V, et Unité Internationale INSERM 743 (Immunologie Humaine), Equipe Immunité et Biothérapie Muqueuse, Centre de Recherches Biomédicales des Cordeliers, Paris, France.

出版信息

Virology. 2008 Jan 20;370(2):246-54. doi: 10.1016/j.virol.2007.09.006. Epub 2007 Oct 24.

Abstract

HIV-1 transcytosis has been proposed as a potential mechanism allowing the virus to cross the epithelium during mucosal transmission. Epitopes of the HIV-1 envelope involved in this process have not been identified yet. Here, we assessed a large panel of HIV neutralizing antibodies recognizing well-characterized epitopes of the HIV-1 envelope for their ability to block HIV-1 transcytosis across a confluent epithelial monolayer. We found that all of the 13 HIV-1-specific monoclonal antibodies tested in the present study, including the three broadly neutralizing antibodies 2F5, 2G12 and IgG1b12, lacked the ability to inhibit transcytosis of cell-free and cell-associated R5- as X4-tropic HIV-1 across a tight and polarized monolayer of HEC-1 epithelial cells. In contrast, anti-gp160 polyclonal antibodies purified from serum or breast milk of HIV-1-infected individuals potently inhibited HIV-1 transcytosis. Furthermore, polymeric S-IgA exhibited similar ability to inhibit transcytosis compared to IgG despite their lower anti-gp160 specific activity. Together, these results demonstrate that the major neutralizing envelope epitopes of HIV-1 are not involved in HIV-1 transcytosis, and suggest that surface agglutination of virus particles may participate to the blocking effect observed with both polyclonal and polymeric anti-gp160 immunoglobulins.

摘要

HIV-1跨细胞转运被认为是病毒在黏膜传播过程中穿过上皮细胞的一种潜在机制。参与这一过程的HIV-1包膜表位尚未确定。在此,我们评估了一大组识别HIV-1包膜特征明确表位的HIV中和抗体,检测它们阻断HIV-1跨汇合上皮单层细胞进行跨细胞转运的能力。我们发现,本研究中测试的所有13种HIV-1特异性单克隆抗体,包括三种广泛中和抗体2F5、2G12和IgG1b12,均缺乏抑制无细胞和细胞相关的R5-及X4嗜性HIV-1跨HEC-1上皮细胞紧密且极化单层细胞进行跨细胞转运的能力。相比之下,从HIV-1感染个体的血清或母乳中纯化的抗gp160多克隆抗体能有效抑制HIV-1跨细胞转运。此外,尽管聚合型S-IgA的抗gp160比活性较低,但其与IgG相比表现出类似的抑制跨细胞转运的能力。总之,这些结果表明,HIV-1主要的中和包膜表位不参与HIV-1跨细胞转运,并提示病毒颗粒的表面凝集可能参与了多克隆和聚合型抗gp160免疫球蛋白所观察到的阻断效应。

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