Identification, characterization, and natural selection of mutations driving airborne transmission of A/H5N1 virus.
Identification, characterization, and natural selection of mutations driving airborne transmission of A/H5N1 virus.
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DOI：
10.1016/j.cell.2014.02.040
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发表时间：
2014-04-10
期刊：
影响因子：
64.5
通讯作者：
Herfst S
中科院分区：
文献类型：
--
作者：
Linster M;van Boheemen S;de Graaf M;Schrauwen EJA;Lexmond P;Mänz B;Bestebroer TM;Baumann J;van Riel D;Rimmelzwaan GF;Osterhaus ADME;Matrosovich M;Fouchier RAM;Herfst S
最近，A/H5N1 流感病毒被证明通过定向诱变和病毒传代获得了雪貂之间的空气传播能力。空中 A/Indonesia/5/05 的关键基因变化尚未确定。在这里，五次替换被证明足以确定这种空气传播表型。 PB1 和 PB2 的取代共同导致转录和病毒复制增强。一种取代提高了 HA 的热稳定性并降低了膜融合的 pH 值。两次取代独立地改变了HA结合偏好，从α2,3连接到α2,6连接的唾液酸受体。 HA 中糖基化位点的丢失增强了与受体的整体结合。获得性替代在雪貂传代过程中早期就以较小的变异形式出现，并迅速成为主导。确定雪貂及其相关表型之间禽流感病毒空气传播所必需的替代品，可以增进我们对病毒传播的基本了解，并将增加未来监测计划和公共卫生风险评估的价值。
Recently, A/H5N1 influenza viruses were shown to acquire airborne transmissibility between ferrets upon targeted mutagenesis and virus passage. The critical genetic changes in airborne A/Indonesia/5/05 were not yet identified. Here, five substitutions proved to be sufficient to determine this airborne transmission phenotype. Substitutions in PB1 and PB2 collectively caused enhanced transcription and virus replication. One substitution increased HA thermostability and lowered the pH of membrane fusion. Two substitutions independently changed HA binding preference from α2,3 linked to α2,6 linked sialic acid receptors. The loss of a glycosylation site in HA enhanced overall binding to receptors. The acquired substitutions emerged early during ferret passage as minor variants and became dominant rapidly. Identification of substitutions that are essential for airborne transmission of avian influenza viruses between ferrets and their associated phenotypes advances our fundamental understanding of virus transmission and will increase the value of future surveillance programs and public health risk assessments.
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影响因子：
3.7
作者：
Chen LM;Blixt O;Stevens J;Lipatov AS;Davis CT;Collins BE;Cox NJ;Paulson JC;Donis RO
通讯作者：
Donis RO
影响因子：
6.7
作者：
Galloway SE;Reed ML;Russell CJ;Steinhauer DA
通讯作者：
Steinhauer DA
影响因子：
56.9
作者：
Shi, Yi;Zhang, Wei;Gao, George F.
通讯作者：
Gao, George F.
影响因子：
168.9
作者：
Claas, ECJ;Osterhaus, ADME;Webster, RG
通讯作者：
Webster, RG
DOI：
10.1073/pnas.94.26.14306
发表时间：
1997-12-23
影响因子：
11.1
作者：
Carr, CM;Chaudhry, C;Kim, PS
通讯作者：
Kim, PS