Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent-resistant membranes and cell-cell fusion but not interaction with M protein.

Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent-resistant membranes and cell-cell fusion but not interaction with M protein.
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DOI:
10.1016/j.virol.2010.05.031
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发表时间:
2010-09-15
期刊:
影响因子:
3.7
通讯作者:
Machamer CE
Machamer CE
中科院分区:
医学3区
文献类型:
--
作者:
McBride CE;Machamer CE

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冠状病毒是包膜RNA病毒,通常在人类中引起轻度疾病。然而,最近出现的导致严重急性呼吸综合征(SARS-CoV)的冠状病毒是迄今为止发现的最具致病性的人类冠状病毒。SARS-CoV刺突(S)蛋白通过结合细胞受体并诱导病毒包膜与宿主细胞膜之间的融合来介导病毒进入。冠状病毒S蛋白是棕榈酰化的,这可能影响功能。在这里,我们通过突变所有9个胞质半胱氨酸残基创建了非棕榈酰化的SARS-CoV S蛋白。SARS-CoV S的棕榈酰化是分配到耐洗涤剂的膜和细胞-细胞融合所必需的。然而,令人惊讶的是,S的棕榈酰化并不是与SARS-CoV M蛋白相互作用所必需的。这与小鼠肝炎病毒S蛋白棕榈酰化与M蛋白相互作用的要求形成对比,并可能指出这两种冠状病毒在组装和感染性方面的重要差异。
Coronaviruses are enveloped RNA viruses that generally cause mild disease in humans. However, the recently emerged coronavirus that caused severe acute respiratory syndrome (SARS-CoV) is the most pathogenic human coronavirus discovered to date. The SARS-CoV spike (S) protein mediates virus entry by binding cellular receptors and inducing fusion between the viral envelope and the host cell membrane. Coronavirus S proteins are palmitoylated, which may affect function. Here, we created a non-palmitoylated SARS-CoV S protein by mutating all nine cytoplasmic cysteine residues. Palmitoylation of SARS-CoV S was required for partitioning into detergent-resistant membranes and for cell–cell fusion. Surprisingly, however, palmitoylation of S was not required for interaction with SARS-CoV M protein. This contrasts with the requirement for palmitoylation of mouse hepatitis virus S protein for interaction with M protein and may point to important differences in assembly and infectivity of these two coronaviruses.
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