Involvement of the mannose receptor in infection of macrophages by influenza virus

Involvement of the mannose receptor in infection of macrophages by influenza virus
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DOI:
10.1128/jvi.74.11.5190-5197.2000
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发表时间:
2000-06-01
影响因子:
5.4
通讯作者:
Anders, EM
Anders, EM
中科院分区:
医学2区
文献类型:
--
作者:
Reading, PC;Miller, JL;Anders, EM

文献摘要

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流感病毒A/PR/8/34(PR8; H1N1),A/Aichi/68 X-31(HKx 31; H3 N2)和A/Beijing/89 X-109(BJx109; 83 N2)在感染鼠巨噬细胞的能力上显示出显著的差异,所述鼠巨噬细胞包括常驻肺泡和腹膜巨噬细胞以及巨噬细胞衍生的细胞系J774,病毒感染性的层次(PR 8 <HK x 31 <BJ x 109)类似于它们与聚集蛋白家族的甘露糖结合凝集素的反应性。由于巨噬细胞甘露糖受体识别的单糖谱与胶原凝集素相同,我们研究了流感病毒感染巨噬细胞中该受体的可能参与。在竞争性结合研究中,I-125标记的甘露糖基化牛血清白蛋白与巨噬细胞的结合被流感病毒的纯化的血凝素和神经氨酸酶(HANA)糖蛋白抑制,但不被用高碘酸盐处理以氧化其寡糖侧链的HANA抑制。来自三种病毒株的HANA的抑制活性显著不同,并且与每种病毒对巨噬细胞的感染性相关。流感病毒对巨噬细胞的感染,而不是MDCK细胞的感染,被酵母甘露聚糖抑制。表达升高水平的甘露糖受体的J773细胞的变体系J774 E比J774更容易感染,和J774 E细胞对感染的敏感性,通过在存在D-甘露糖的情况下培养大大降低,其下调甘露糖受体表达。总之,这些数据暗示甘露糖受体作为流感病毒和可能其他包膜病毒感染性进入小鼠巨噬细胞的主要内吞受体。
Influenza viruses A/PR/8/34 (PR8; H1N1), A/Aichi/68 X-31 (HKx31; H3N2), and A/Beijing/89 X-109 (BJx109; 83N2) show marked differences in their ability to infect murine macrophages, including resident alveolar and peritoneal macrophages as well as the macrophage-derived cell line J774, The hierarchy in infectivity of the viruses (PR8 < HKx31 < BJx109) resembles that of their reactivity with mannose-binding lectins of the collectin family. Since the macrophage mannose receptor recognizes the same spectrum of monosaccharides as the collectins do, we investigated the possible involvement of this receptor in infection of macrophages by influenza virus. In competitive binding studies, the binding of I-125-labeled mannosylated bovine serum albumin to macrophages was inhibited by the purified hemagglutinin and neuraminidase (HANA) glycoproteins of influenza virus but not by HANA that had been treated with periodate to oxidize its oligosaccharide side chains. The inhibitory activity of HANA from the three strains of virus differed markedly and correlated with the infectivity of each virus for macrophages, Infection of macrophages, but not MDCK cells, by influenza virus was inhibited by yeast mannan, A variant line of J773 cells, J774E, which expresses elevated levels of the mannose receptor, was more readily infected than J774, and the sensitivity of J774E cells to infection,vas greatly reduced by culture in the presence of D-mannose, which down-modulated mannose receptor expression. Together, the data implicate the mannose receptor as a major endocytic receptor in the infectious entry of influenza virus, and perhaps other enveloped viruses, into murine macrophages.