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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Activation of EGFR on monocytes is required for human cytomegalovirus entry and mediates cellular motility
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Activation of EGFR on monocytes is required for human cytomegalovirus entry and mediates cellular motility

机译：人巨细胞病毒进入需要单核细胞上的EGFR激活并介导细胞运动

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摘要

Human cytomegalovirus (HCMV) rapidly induces a mobile and functionally unique proinf lammatory monocyte following infection that is proposed to mediate viral spread. The cellular pathways used by HCMV to initiate these biological changes remain unknown. Here, we document the expression of the epidermal growth factor receptor (EGFR) on the surface of human peripheral blood monocytes but not on other blood leukocyte populations. Inhibition of EGFR signaling abrogated viral entry into monocytes, indicating that EGFR can serve as a cellular tropism receptor. Moreover, HCMV-activated EGFR was required for the induction of monocyte motility and transendothelial migration, two biological events required for monocyte extravasation into peripheral tissue, and thus viral spread. Transcriptome analysis revealed that HCMV-mediated EGFR signaling up-regulated neural Wiskott-Aldrich syndrome protein (N-WASP), an actin nucle-ator whose expression and function are normally limited in leukocytes. Knockdown of N-WASP expression blocked HCMV-induced but not phorbol 12-myristate 13-acetate (PMA)-induced monocyte motility, suggesting that a switch to and/or the distinct use of a new actin nucleator controlling motility occurs during HCMV infection of monocytes. Together, these data provide evidence that EGFR plays an essential role in the immunopathobiology of HCMV by mediating viral entry into monocytes and stimulating the aberrant biological activity that promotes hematogenous dissemination.
机译：人巨细胞病毒（HCMV）在感染后迅速诱导出可移动的和功能独特的促炎性单核前单核细胞，并提议其介导病毒传播。 HCMV用于引发这些生物学变化的细胞途径仍然未知。在这里，我们记录了人类外周血单核细胞表面上的表皮生长因子受体（EGFR）的表达，但在其他血液白细胞群体上却没有。 EGFR信号转导的抑制使病毒进入单核细胞中止，表明EGFR可以用作细胞嗜性受体。此外，HCMV激活的EGFR是诱导单核细胞运动性和跨内皮迁移所必需的，这是单核细胞渗入周围组织并因此传播病毒所需的两个生物学事件。转录组分析显示，HCMV介导的EGFR信号上调了神经Wiskott-Aldrich综合征蛋白（N-WASP），这是一种肌动蛋白成核剂，其表达和功能通常在白细胞中受到限制。击倒N-WASP表达可阻止HCMV诱导，但不能阻止佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）诱导的单核细胞运动，这表明在HCMV感染过程中发生了向新的肌动蛋白成核剂控制运动的转换和/或不同用途。单核细胞。总之，这些数据提供了证据，表明EGFR通过介导病毒进入单核细胞并刺激异常的生物活性（促进血源性传播）而在HCMV的免疫病理学中发挥重要作用。

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    Gary Chan; Maciej T. Nogalski; Andrew D. Yurochko;

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    Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Shreveport, LA 71130-3932;

    Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Shreveport, LA 71130-3932;

    Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Shreveport, LA 71130-3932 Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932 Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130 3932;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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