The location of asparagine-linked glycans on West Nile virions controls their interactions with CD209 (dendritic cell-specific ICAM-3 grabbing nonintegrin)
The location of asparagine-linked glycans on West Nile virions controls their interactions with CD209 (dendritic cell-specific ICAM-3 grabbing nonintegrin)
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DOI：
10.1074/jbc.m605429200
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发表时间：
2006-12-01
影响因子：
4.8
通讯作者：
Pierson, Theodore C.
中科院分区：
文献类型：
--
作者：
Davis, Carl W.;Mattei, Lisa M.;Pierson, Theodore C.
哺乳动物细胞来源的西尼罗病毒优先感染表达C型凝集素CD 209 L（树突细胞特异性ICAM-3抓取非整联蛋白相关蛋白;肝和淋巴结特异性ICAM-3抓取非整联蛋白）的细胞，但不感染表达CD 209（树突细胞特异性ICAM-3抓取非整联蛋白）的细胞。相反，登革病毒感染在表达任一附着因子的细胞中增强。西尼罗病毒包膜（E）蛋白在残基154处含有单个N-连接的糖基化位点，而登革病毒E在残基153和67处含有位点。我们在西尼罗病毒E的第67位引入了一个糖基化位点。使用CD 209或CD 209 L用该E蛋白假型化的报告病毒颗粒感染细胞。我们还在几个新的位置引入了糖基化位点。所有部位均允许CD 209 L介导的感染，但只有一个亚组促进了CD 209的使用。与其他病毒一样，西尼罗河病毒上富含甘露糖的聚糖是其与CD 209相互作用所必需的。然而，令人惊讶的是，富含甘露糖的聚糖不是CD 209 L介导的感染所必需的。复杂的聚糖，特别是N-乙酰葡糖胺封端的结构，能够介导报告病毒颗粒与CD 209 L的相互作用。我们提出，CD 209 L识别糖基化黄病毒具有广泛的特异性，而CD 209是选择性的黄病毒轴承富含甘露糖聚糖。病毒粒子上N-连接糖基化位点的位置决定了掺入的聚糖类型，从而控制了病毒对表达CD 209的细胞的嗜性。
Mammalian cell-derived West Nile virus preferentially infects cells expressing the C-type lectin CD209L (dendritic cell-specific ICAM-3 grabbing nonintegrin-related protein; liver- and lymph node-specific ICAM-3 grabbing nonintegrin) but not cells expressing CD209 (dendritic cell-specific ICAM-3 grabbing nonintegrin). In contrast, Dengue virus infection is enhanced in cells expressing either attachment factor. The West Nile virus envelope (E) protein contains a single N-linked glycosylation site at residue 154, whereas Dengue virus E contains sites at residues 153 and 67. We introduced a glycosylation site at position 67 into West Nile virus E. Reporter virus particles pseudotyped with this E protein infected cells using either CD209 or CD209L. We also introduced glycosylation sites at several novel positions. All sites allowed CD209L-mediated infection, but only a subset promoted CD209 use. As seen for other viruses, mannose-rich glycans on West Nile virus were required for its interactions with CD209. Surprisingly, however, mannose-rich glycans were not required for CD209L-mediated infection. Complex glycans, particularly N-acetylglucosamine-terminated structures, were able to mediate reporter virus particle interactions with CD209L. We propose that CD209L recognizes glycosylated flaviviruses with broad specificity, whereas CD209 is selective for flaviviruses bearing mannose-rich glycans. The location of the N-linked glycosylation sites on a virion determines the types of glycans incorporated, thus controlling viral tropism for CD209-expressing cells.