Influenza virus assembly and budding in raft-derived microdomains: A quantitative analysis of the surface distribution of HA, NA and M2 proteins
Influenza virus assembly and budding in raft-derived microdomains: A quantitative analysis of the surface distribution of HA, NA and M2 proteins
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DOI：
10.1016/j.virol.2005.09.049
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发表时间：
2005-11-25
期刊：
影响因子：
3.7
通讯作者：
Lamb, RA
中科院分区：
文献类型：
--
作者：
Leser, GP;Lamb, RA
流感病毒血凝素(HA)和神经氨酸酶(NA)与脂筏相关，脂筏是由紧密堆积的胆固醇和鞘磷脂组成的膜微域。这些特殊的膜区被认为参与了包括流感病毒在内的许多包膜病毒的萌发。用免疫金染色法对病毒感染细胞表面HA分布的定量分析表明，感染后随着HA表达水平的增加，组织成簇(P.I.)(类似于4h P.I.时的325-500 nm在6hP.I.时类似于425-600 nm)。这些含有HA的簇很可能来自脂筏，因为它们含有高密度的RAFT标记神经节苷脂GM1，并依赖于胆固醇的存在。HA的聚集性是HA蛋白的一种固有特性，在没有其他病毒蛋白表达的情况下发生。NA也被发现隔离在与HA相同的微域中，而M2离子通道蛋白并不集中在RAFT样微域中。通过检查病毒感染细胞的连续切片对表面表达的HA的分布进行了量化，表明含有HA的微域产生了流感组装和萌芽的区域。(C)2005 Elsevier Inc.保留所有权利。
Influenza virus hemagglutinin (HA) and neuraminidase (NA) are known to associate with lipid rafts, membrane microdomains comprised of densely packed cholesterol and sphingolipids. These specialized membrane regions are believed to be involved in the budding of many enveloped viruses including influenza virus. Quantitative analysis of HA distribution on the surface of virus-infected cells by immunogold staining shows an organization into clusters that grow in size as the expression level of HA increases with time post-infection (p.i.) (similar to 325-500 nm at 4 h p.i. and similar to 425-600 nm at 6 h p.i.). These HA-containing clusters are likely derived from lipid rafts as they contain a high density of the raft marker ganglioside GM 1 and are dependent upon the presence of cholesterol. The clustering of HA is an intrinsic property of the HA protein and occurs in the absence of expression of other viral proteins. NA is also found sequestered within the same microdomains as HA, whereas the M2 ion channel protein does not concentrate within the raft-like microdomains. Quantification of the distribution of surface expressed HA by examining serial sections of virus-infected cells suggests that the HA-containing microdomains give rise to regions of influenza assembly and budding. (c) 2005 Elsevier Inc. All rights reserved.