Measles viruses with altered envelope protein cytoplasmic tails gain cell fusion competence
Measles viruses with altered envelope protein cytoplasmic tails gain cell fusion competence
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DOI：
10.1128/jvi.72.2.1224-1234.1998
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发表时间：
1998-02-01
影响因子：
5.4
通讯作者：
Cattaneo, R
中科院分区：
文献类型：
--
作者：
Cathomen, T;Naim, HY;Cattaneo, R
在亚急性硬化性泛脑炎(SSPE)患者的脑内传播的病毒中，麻疹病毒(MV)融合蛋白(F)的细胞质尾部经常发生改变。我们将SSPE病毒F尾的编码区转移到了MV基因组的cDNA中。同样，我们构建并转移了另一种病毒糖蛋白血凝素(H)基因的突变尾部编码区，从突变的基因组cDNA中，我们实现了拯救具有不同F尾部变化的病毒、H尾部远端膜上的缺失以及这些突变的组合，任何尾部发生变化的病毒通过增强的细胞-细胞融合通过单层迅速传播。双尾突变体具有更高的融合能力，但感染性略有降低。对释放的突变病毒颗粒的蛋白质组成分析表明，尾巴是准确组装病毒包膜所必需的，并提示存在直接的F尾-基质(M)蛋白相互作用。由于即使是尾巴改变的糖蛋白与M蛋白共定位在细胞内斑块中，也可能存在额外的相互作用。我们的结论是，在包括SSPE在内的MV感染中，糖蛋白尾部不仅参与病毒包膜的组装，还参与控制病毒诱导的细胞融合。
The cytoplasmic tail of the measles virus (MV) fusion (F) protein is often altered in viruses which spread through the brain of patients suffering from subacute sclerosing panencephalitis (SSPE). We transferred the coding regions of F tails from SSPE viruses in an MV genomic cDNA. Similarly, we constructed and transferred mutated tail-encoding regions of the other viral glycoprotein hemagglutinin (H) gene, From the mutated genomic cDNAs, we achieved rescue of viruses that harbor different alterations of the F tail, deletions in the membrane distal half of the H tail, and combinations of these mutations, Viruses with alterations in any of the tails spread rapidly through the monolayer via enhanced cell-cell fusion. Double-tail mutants had even higher fusion competence but slightly decreased infectivity. Analysis of the protein composition of released mutant viral particles indicated that the tails are necessary for accurate virus envelope assembly and suggested a direct F tail-matrix (M) protein interaction. Since even tail-altered glycoproteins colocalized with M protein in intracellular patches, additional interactions may exist. We conclude that in MV infections, including SSPE, the glycoprotein tails are involved not only in virus envelope assembly but also in the control of virus-induced cell fusion.