Influenza virus entry and infection require host cell N-linked glycoprotein
Influenza virus entry and infection require host cell N-linked glycoprotein
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DOI：
10.1073/pnas.0405172102
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发表时间：
2004-12-28
影响因子：
11.1
通讯作者：
Whittaker, GR
中科院分区：
文献类型：
--
作者：
Chu, VC;Whittaker, GR
关于流感病毒感染的一个广泛持有的观点是，病毒受体由细胞表面碳水化合物唾液酸组成，其可以糖蛋白或糖脂的形式存在。在这里，我们研究了流感病毒进入和感染的Lec 1细胞，一个突变的CHO细胞系缺乏在N-乙酰氨基葡萄糖转移酶I（GnT 1）基因突变引起的末端N-连接糖基化。我们发现，流感病毒不能感染Lec 1细胞，尽管有充分的能力进行病毒结合和融合。Lec 1细胞也没有显示病毒复制缺陷，并且在表达野生型GnT 1的Lec 1细胞中恢复了感染。病毒显然是在从质膜内化的水平上被捕获的，并且没有被内吞。Lec 1细胞对几种流感病毒株的感染是难治的，包括甲型流感的H1和H3株，以及B流感病毒。最后，来自野生型CHO细胞的N-聚糖的裂解显著降低了流感病毒的感染。我们认为，流感病毒特别需要Winked糖蛋白进入细胞，唾液酸，虽然作为一个有效的附着因子，是不足以作为流感病毒受体在体内。
A widely held view of influenza virus infection is that the viral receptor consists of cell surface carbohydrate sialic acid, which can be present as glycoprotein or glycolipid. Here, we examined influenza virus entry and infection in Lec1 cells, a mutant CHO cell line deficient in terminal N-linked glycosylation caused by a mutation in the N-acetylglucosaminyltransferase I (GnT1) gene. We show that influenza virus cannot infect Lec1 cells, despite having full capacity to undergo virus binding and fusion. Lec1 cells also show no virus replication defect, and infection was restored in Lec1 cells expressing wild-type GnT1. Viruses were apparently arrested at the level of internalization from the plasma membrane and were not endocytosed. Lec1 cells were refractory to infection by several strains of influenza virus, including H1 and H3 strains of influenza A, as well as influenza B virus. Finally, cleavage of N-glycans from wild-type CHO cells markedly reduced infection by influenza virus. We suggest that influenza virus specifically requires Winked glycoprotein for entry into cells, and that sialic acid, although acting as an efficient attachment factor, is not sufficient as an influenza virus receptor in vivo.