The Fusion Protein Specificity of the Parainfluenza Virus Hemagglutinin-Neuraminidase Protein Is Not Solely Defined by the Primary Structure of Its Stalk Domain
The Fusion Protein Specificity of the Parainfluenza Virus Hemagglutinin-Neuraminidase Protein Is Not Solely Defined by the Primary Structure of Its Stalk Domain
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DOI：
10.1128/jvi.01448-15
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发表时间：
2015-12-01
影响因子：
5.4
通讯作者：
Nosaka, Tetsuya
中科院分区：
文献类型：
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作者：
Tsurudome, Masato;Ito, Morihiro;Nosaka, Tetsuya
附着蛋白（HN）和融合蛋白(F)之间的病毒特异性相互作用是诱导副流感病毒膜融合的先决条件。这种HN-F相互作用可能是由HN柄结构域和F头结构域的特定氨基酸介导的。然而，我们在本研究中发现，类人猿41病毒（SV41） F特异性嵌合HPIV2 HN蛋白SCA，其细胞质、跨膜和茎结构域来源于SV41 HN蛋白，当与SV41 HN特异性嵌合PIV5 F蛋白共表达时，不能诱导BHK-21细胞的细胞融合。36. 同样，sv41hn蛋白的无头形式未能诱导与嵌合体no的融合。而能诱导与sv41f蛋白的融合。有趣的是，将位于SCA头结构域二聚体界面或周围的13个氨基酸替换为SV41 HN对应物，产生嵌合的HN蛋白SCA- rii，诱导与嵌合体no融合。而sv41f蛋白则没有。更有趣的是，将SCA- rii的13个氨基酸中的11个与SCA对应的氨基酸进行反向替换，产生了另一个嵌合的HN蛋白IM18，该蛋白诱导了与嵌合体no - rii的融合。36或SV41 F蛋白，类似于SV41 HN蛋白。因此，我们得出结论，在融合事件中观察到的HN蛋白的F蛋白特异性并不仅仅由HN柄结构域的初级结构决定。值得注意的是，HN头部结构域最初隐藏HN柄结构域，但在头部结构域与受体结合后暴露它，这允许柄结构域中的特定氨基酸与F蛋白相互作用并触发其诱导融合。然而，HN头部结构域在融合事件中的其他调节作用尚未明确。我们在目前的研究中表明，去除头部结构域或在头部结构域的特定区域替换氨基酸会极大地改变HN蛋白的F蛋白特异性，这表明给定HN蛋白与F蛋白相互作用的能力不仅由HN柄结构域的初级结构决定，而且由其构象决定。这一概念似乎解释了风疹病毒HN蛋白在触发非同源F蛋白时的单向可替代性。
Virus-specific interaction between the attachment protein (HN) and the fusion protein (F) is prerequisite for the induction of membrane fusion by parainfluenza viruses. This HN-F interaction presumably is mediated by particular amino acids in the HN stalk domain and those in the F head domain. We found in the present study, however, that a simian virus 41 (SV41) F-specific chimeric HPIV2 HN protein, SCA, whose cytoplasmic, transmembrane, and stalk domains were derived from the SV41 HN protein, could not induce cell-cell fusion of BHK-21 cells when coexpressed with an SV41 HN-specific chimeric PIV5 F protein, no. 36. Similarly, a headless form of the SV41 HN protein failed to induce fusion with chimera no. 36, whereas it was able to induce fusion with the SV41 F protein. Interestingly, replacement of 13 amino acids of the SCA head domain, which are located at or around the dimer interface of the head domain, with SV41 HN counterparts resulted in a chimeric HN protein, SCA-RII, which induced fusion with chimera no. 36 but not with the SV41 F protein. More interestingly, retroreplacement of 11 out of the 13 amino acids of SCA-RII with the SCA counterparts resulted in another chimeric HN protein, IM18, which induced fusion either with chimera no. 36 or with the SV41 F protein, similar to the SV41 HN protein. Thus, we conclude that the F protein specificity of the HN protein that is observed in the fusion event is not solely defined by the primary structure of the HN stalk domain.IMPORTANCEIt is appreciated that the HN head domain initially conceals the HN stalk domain but exposes it after the head domain has bound to the receptors, which allows particular amino acids in the stalk domain to interact with the F protein and trigger it to induce fusion. However, other regulatory roles of the HN head domain in the fusion event have been ill defined. We have shown in the current study that removal of the head domain or amino acid substitutions in a particular region of the head domain drastically change the F protein specificity of the HN protein, suggesting that the ability of a given HN protein to interact with an F protein is defined not only by the primary structure of the HN stalk domain but also by its conformation. This notion seems to account for the unidirectional substitutability among rubulavirus HN proteins in triggering noncognate F proteins.