Vaccinia virus F9 virion membrane protein is required for entry but not virus assembly, in contrast to the related L1 protein
Vaccinia virus F9 virion membrane protein is required for entry but not virus assembly, in contrast to the related L1 protein
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DOI：
10.1128/jvi.01149-06
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发表时间：
2006-10-01
影响因子：
5.4
通讯作者：
Moss, Bernard
中科院分区：
文献类型：
--
作者：
Brown, Erica;Senkevich, Tatiana G.;Moss, Bernard
所有测序的痘病毒编码牛痘病毒L1和F9蛋白的直系同源物，它们在结构上相似，并且共享约20%的氨基酸同一性。我们发现F9进一步类似于L1，因为这两种蛋白质都是具有相似拓扑结构的成熟病毒体的膜组分，并诱导中和抗体。此外，诱导表达F9的重组牛痘病毒，如先前描述的L1突变体，具有条件致死表型：感染性病毒的噬斑形成和复制依赖于添加的诱导剂。然而，当L1被抑制时，仅产生不成熟的病毒颗粒，而在不存在F9的情况下，形成正常外观的细胞内和细胞外病毒体。除了缺乏F9外，这些病毒粒子的多肽组分与野生型病毒的多肽组分难以区分。这些F9缺陷型病毒粒子与细胞结合，但它们的核心不穿透细胞质。此外，用F9阴性病毒体感染的细胞在短暂的低pH处理后不融合，如用在诱导剂存在下制备的病毒感染的细胞一样。在这些方面，与F9缺陷相关的表型与缺乏先前描述的痘病毒进入/融合复合物的单个组分所产生的表型相同。此外，F9与该复合物的蛋白质相互作用，支持相关的作用。因此，尽管L1和F9的结构关系，这两种蛋白质具有不同的功能，分别在组装和进入。
All sequenced poxviruses encode orthologs of the vaccinia virus L1 and F9 proteins, which are structurally similar and share about 20% amino acid identity. We found that F9 further resembles L1 as both proteins are membrane components of the mature virion with similar topologies and induce neutralizing antibodies. In addition, a recombinant vaccinia virus that inducibly expresses F9, like a previously described L1 mutant, had a conditional-lethal phenotype: plaque formation and replication of infectious virus were dependent on added inducer. However, only immature virus particles are made when L1 is repressed, whereas normal-looking intracellular and extracellular virions formed in the absence of F9. Except for the lack of F9, the polypeptide components of such virions were indistinguishable from those of wild-type virus. These F9-deficient virions bound to cells, but their cores did not penetrate into the cytoplasm. Furthermore, cells infected with F9-negative virions did not fuse after a brief low-pH treatment, as did cells infected with virus made in the presence of inducer. In these respects, the phenotype associated with F9 deficiency was identical to that produced by the lack of individual components of a previously described poxvirus entry/fusion complex. Moreover, F9 interacted with proteins of that complex, supporting a related role. Thus, despite the structural relationships of L1 and F9, the two proteins have distinct functions in assembly and entry, respectively.