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首页> 外文期刊>AIDS Research and Human Retroviruses >Antibody against integrin lymphocyte function-associated antigen 1 inhibits HIV type 1 infection in primary cells through caspase-8-mediated apoptosis
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Antibody against integrin lymphocyte function-associated antigen 1 inhibits HIV type 1 infection in primary cells through caspase-8-mediated apoptosis

机译：整合素淋巴细胞功能相关抗原1抗体通过caspase-8介导的凋亡抑制原代细胞中的HIV 1型感染

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摘要

HIV-1 infection induces formation of a virological synapse wherein CD4, chemokine receptors, and cell-adhesion molecules such as lymphocyte function-associated antigen 1 (LFA-1) form localized domains on the cell surface. Studies show that LFA-1 on the surface of HIV-1 particles retains its adhesion function and enhances virus attachment to susceptible cells by binding its counterreceptor intercellular adhesion molecule 1 (ICAM-1). This virus-cell interaction augments virus infectivity by facilitating binding and entry events. In this study, we demonstrate that inhibition of the LFA-1/ICAM-1 interaction by a monoclonal antibody leads to decreased virus production and spread in association with increased apoptosis of HIV-infected primary T cells. The data indicate that the LFA-1/ICAM-1 interaction may limit apoptosis in HIV-1-infected T cells. This phenomenon appears similar to anoikis wherein epithelial cells are protected from apoptosis conferred by ligand-bound integrins. These results have implications for further understanding HIV pathogenesis and replication in peripheral compartments and lymphoid organs.
机译：HIV-1感染诱导病毒突触的形成，其中CD4，趋化因子受体和细胞粘附分子（如淋巴细胞功能相关抗原1（LFA-1））在细胞表面形成局部结构域。研究表明，HIV-1颗粒表面的LFA-1通过结合其反受体细胞间粘附分子1（ICAM-1）保持其粘附功能并增强病毒与易感细胞的附着。这种病毒与细胞的相互作用通过促进结合和进入事件而增强了病毒的传染性。在这项研究中，我们证明了单克隆抗体对LFA-1 / ICAM-1相互作用的抑制会导致病毒产生和传播减少，并伴随HIV感染的原代T细胞凋亡增加。数据表明，LFA-1 / ICAM-1相互作用可能会限制感染HIV-1的T细胞的凋亡。这种现象似乎类似于无神经症，其中上皮细胞受到保护，免受配体结合的整联蛋白赋予的凋亡。这些结果对进一步了解HIV在周围区室和淋巴器官中的发病机理和复制具有启示意义。

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