Late domain function identified in the vesicular stomatitis virus M protein by use of rhabdovirus-retrovirus chimeras
Late domain function identified in the vesicular stomatitis virus M protein by use of rhabdovirus-retrovirus chimeras
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DOI：
10.1128/jvi.73.4.3359-3365.1999
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发表时间：
1999-04-01
影响因子：
5.4
通讯作者：
Wills, JW
中科院分区：
文献类型：
--
作者：
Craven, RC;Harty, RN;Wills, JW
关于包膜病毒在出芽的最后一步将自身与细胞表面分离的机制，我们知之甚少。然而，几种逆转录病毒的Gag蛋白（L结构域）中的小序列与此过程有关。已经在弹状病毒的M蛋白中鉴定出与劳斯肉瘤病毒（RSV）（一种禽类逆转录病毒）的L结构域中的PPPPY基序非常相似的序列。为了评价水泡性口炎病毒（VSV）M蛋白中的PPPY序列是否具有与逆转录病毒序列类似的活性，表征了M-Gag嵌合体。VSV（印第安纳州）M蛋白的N-末端74个氨基酸（包括PPPY基序）能够替换RSV Gag的L结构域并允许病毒样颗粒的组装和释放。丙氨酸取代VSV PPPY基序严重损害了这种杂合蛋白的出芽活性，但不是另一种嵌合体，也含有RSV PPPPY序列。我们的结论是，该VSV序列在促进病毒颗粒释放方面与RSV L结构域在功能上同源，这是在逆转录病毒以外的病毒中具有这种活性的第一个例子。RSV和VSV基序都已显示在体外与含有WW相互作用模块的某些细胞蛋白相互作用，表明L结构域是与参与病毒释放的未知宿主机制相互作用的位点。
Little is known about the mechanisms used by enveloped viruses to separate themselves from the cell surface at the final step of budding. However, small sequences in the Gag proteins of several retroviruses (L domains) have been implicated in this process. A sequence has been identified in the M proteins of rhabdoviruses that closely resembles the PPPPY motif in the L domain of Rous sarcoma virus (RSV), an avian retrovirus. To evaluate whether the PPPY sequence in vesicular stomatitis virus (VSV) M protein has an activity analogous to that of the retroviral sequence, M-Gag chimeras were characterized. The N-terminal 74 amino acids of the VSV (Indiana) M protein, including the PPPY motif, was able to replace the L domain of RSV Gag and allow the assembly and release of virus-like particles. Alanine substitutions in the VSV PPPY motif severely compromised the budding activity of this hybrid protein but not that of another chimera which also contained the RSV PPPPY sequence. We conclude that this VSV sequence is functionally homologous to the RSV L domain in promoting virus particle release, making this the first example of such an activity in a virus other than a retrovirus. Both the RSV and VSV motifs have been shown to interact in vitro with certain cellular proteins that contain a WW interaction module, suggesting that the L domains are sites of interaction with unknown host machinery involved in virus release.