Congregation of Orthopoxvirus Virions in Cytoplasmic A-Type Inclusions Is Mediated by Interactions of a Bridging Protein (A26p) with a Matrix Protein (ATIp) and a Virion Membrane-Associated Protein (A27p)
Congregation of Orthopoxvirus Virions in Cytoplasmic A-Type Inclusions Is Mediated by Interactions of a Bridging Protein (A26p) with a Matrix Protein (ATIp) and a Virion Membrane-Associated Protein (A27p)
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DOI：
10.1128/jvi.00704-10
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发表时间：
2010-08-01
影响因子：
5.4
通讯作者：
Moss, Bernard
中科院分区：
文献类型：
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作者：
Howard, Amanda R.;Weisberg, Andrea S.;Moss, Bernard
一些正痘病毒，如牛痘、外痘和浣熊痘病毒，形成大的、离散的细胞质内含物，成熟的病毒粒子(MV)通过一种称为闭塞的过程嵌入其中。这些包涵体可能保护环境中闭塞的MVS，由A-型包涵体蛋白(ATIP)聚集体组成，ATIP在痘苗病毒(VACV)和天花病毒等不能形成包涵体的正痘病毒中被截短。除了完整的ATIP外，闭塞还需要A26蛋白(A26p)。虽然VACV包含一个功能性的A26p，由牛痘病毒封闭缺陷突变体的互补决定，但它在封闭中的作用尚不清楚。我们发现，修复全长ATI基因足以形成VACV包涵体，并随后闭塞MVS。A26P即使在病毒粒子组装被抑制的情况下也存在于包涵体中，表明A26P与ATIP直接相互作用。对一组ATIP突变体的分析表明，C-末端重复区域是形成包涵体所必需的，N-末端结构域是与A26P相互作用和封闭所必需的。A26p通过与A27蛋白(A27p)相互作用与MVS结合；A27p不是A26p与ATIP结合所必需的，但对于闭塞是必需的。此外，介导A26p-A27p相互作用的A26p的C-末端结构域对于闭塞来说是必要的，但不够。综上所述，这些数据提出了一种闭塞模型，在该模型中，A26p在ATIP和A27p之间起桥梁作用，A27p提供到MV膜的连接。
Some orthopoxviruses, e.g., the cowpox, ectromelia, and raccoonpox viruses, form large, discrete cytoplasmic inclusions within which mature virions (MVs) are embedded by a process called occlusion. These inclusions, which may protect occluded MVs in the environment, are composed of aggregates of the A-type inclusion protein (ATIp), which is truncated in orthopoxviruses such as vaccinia virus (VACV) and variola virus that fail to form inclusions. In addition to an intact ATIp, occlusion requires the A26 protein (A26p). Although VACV contains a functional A26p, determined by complementation of a cowpox virus occlusion-defective mutant, its role in occlusion was unknown. We found that restoration of the full-length ATI gene was sufficient for VACV inclusion formation and the ensuing occlusion of MVs. A26p was present in inclusions even when virion assembly was inhibited, suggesting a direct interaction of A26p with ATIp. Analysis of a panel of ATIp mutants indicated that the C-terminal repeat region was required for inclusion formation and the N-terminal domain for interaction with A26p and occlusion. A26p is tethered to MVs via interaction with the A27 protein (A27p); A27p was not required for association of A26p with ATIp but was necessary for occlusion. In addition, the C-terminal domain of A26p, which mediates A26p-A27p interactions, was necessary but insufficient for occlusion. Taken together, the data suggest a model for occlusion in which A26p has a bridging role between ATIp and A27p, and A27p provides a link to the MV membrane.