Dengue virus binding to human leukocyte cell lines: receptor usage differs between cell types and virus strains

Dengue virus binding to human leukocyte cell lines: receptor usage differs between cell types and virus strains
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DOI:
10.1016/s0168-1702(00)00233-1
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发表时间:
2001-01-01
期刊:
影响因子:
5
通讯作者:
Mackenzie, JS
Mackenzie, JS
中科院分区:
医学3区
文献类型:
--
作者:
Bielefeldt-Ohmann, H;Meyer, M;Mackenzie, JS

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单核巨噬细胞(M phi)被认为是登革热病毒(DV)的主要靶细胞,DV是登革热和出血热的病因。细胞附着是由病毒包膜(E)蛋白介导的,但宿主细胞受体仍然难以捉摸。目前,候选受体分子包括蛋白质、Fc受体、糖胺聚糖(GAG)和脂多糖结合CD 14相关分子。在这里,我们表明,除了M phi,T细胞和B细胞谱系的细胞,包括缺乏GAG的细胞,可以结合并感染DV。病毒结合的水平在细胞系之间变化很大,特别是在DV血清型内的病毒株之间。后一种差异可归因于E蛋白的结构域II中的一个或多个氨基酸差异。肝素对DV结合没有显著影响,而在所有情况下肝素酶处理细胞增加DV结合,进一步支持GAG对于DV结合和人细胞感染不是必需的论点。与最近的报道相反,我们发现脂多糖(LPS)对各种人白细胞系的DV结合和感染没有影响或增强,而在所有病毒-细胞组合中,Ca 2 +/Mg 2+的耗尽增强DV结合。这与β 2整联蛋白参与病毒-宿主细胞相互作用的观点相反,这一结论与三种< 75 kDa的病毒结合膜蛋白的证明雅阁。总的来说,本研究的结果质疑了E蛋白结构域III在DV与宿主细胞结合中的独特重要性,并指出了各种靶细胞之间,特别是个别DV毒株之间更为复杂的相互作用。(C)2001 Elsevier Science B. V.保留所有权利。
Monocyte macrophages (M phi) are thought to be the principal target cells for the dengue viruses (DV), the cause of dengue fever and hemorrhagic fever. Cell attachment is mediated by the virus envelope (E) protein, but the host-cell receptors remain elusive. Currently, candidate receptor molecules include proteins, Fc receptors, glycosaminoglycans (GAGs) and lipopolysaccharide binding CD14-associated molecules. Here, we show that in addition to M phi, cells of the T- and B-cell lineages, and including cells lacking GAGs, can bind and become infected with DV. The level of virus binding varied widely between cell lines and, notably, between virus strains within a DV serotype. The latter difference may be ascribable to one or more amino acid differences in domain II of the E protein. Heparin had no significant effect on DV binding, while heparinase treatment of cells in all cases increased DV binding, further supporting the contention that GAGs are not required for DV binding and infection of human cells. In contrast to a recent report, we found that lipopolysaccharide (LPS) had either no effect or enhanced DV binding to, and infection of various human leukocyte cell lines, while in all virus-cell combinations, depletion of Ca2+/Mg2+ enhanced DV binding. This argues against involvement of beta (2) integrins in virus-host cell interactions, a conclusion in accord with the demonstration of three virus binding membrane proteins of < 75 kDa. Collectively, the results of this study question the purported exclusive importance of the E protein domain III in DV binding to host cells and point to a far more complex interaction between various target cells and, notably, individual DV strains. (C) 2001 Elsevier Science B.V. All rights reserved.