Intergenotypic Replacement of Lyssavirus Matrix Proteins Demonstrates the Role of Lyssavirus M Proteins in Intracellular Virus Accumulation
Intergenotypic Replacement of Lyssavirus Matrix Proteins Demonstrates the Role of Lyssavirus M Proteins in Intracellular Virus Accumulation
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DOI：
10.1128/jvi.01665-09
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发表时间：
2010-02-15
影响因子：
5.4
通讯作者：
Mettenleiter, Thomas C.
中科院分区：
文献类型：
--
作者：
Finke, Stefan;Granzow, Harald;Mettenleiter, Thomas C.
Lyssavirus装配依赖于基质蛋白（M）。我们比较了来自不同基因型的狂犬病病毒M蛋白支持基因型1狂犬病病毒（RABV）组装和外出的能力。M缺陷型RABV与来自欧洲蝙蝠狂犬病病毒（EBLV）1型和2型的M的反式互补减少了感染性病毒的释放。将异基因型M蛋白稳定引入RABV导致嵌合病毒，其具有减少的病毒释放和病毒基因组的细胞内积累。虽然嵌合体表明M的基因型特异性进化，但补偿突变体的快速选择表明狂犬病毒属病毒组装的保守机制，并且仅需要很少的适应性突变来适应RABV骨架的异基因型M。而补偿突变体复制到类似的感染滴度RABV M表达病毒，超微结构分析表明，无论是非适应EBLV M嵌合体和补偿突变体不同的RABV M表达病毒在缺乏细胞内的病毒样结构，包膜和积累在池的脱粒和扩张的粗面内质网室。此外，所有病毒都能在质膜上出芽。由于细胞内病毒样结构的缺乏与M蛋白的类型相关，但与病毒释放的效率无关，因此我们假设EBLV-1和RABV的M蛋白在其用于病毒组装的靶膜上不同。虽然细胞内组装和积累的病毒样结构在内质网中的生物学功能仍然不清楚，所观察到的差异可能有助于不同的宿主向性或致病性。
Lyssavirus assembly depends on the matrix protein (M). We compared lyssavirus M proteins from different genotypes for their ability to support assembly and egress of genotype 1 rabies virus (RABV). Transcomplementation of M-deficient RABV with M from European bat lyssavirus (EBLV) types 1 and 2 reduced the release of infectious virus. Stable introduction of the heterogenotypic M proteins into RABV led to chimeric viruses with reduced virus release and intracellular accumulation of virus genomes. Although the chimeras indicated genotype-specific evolution of M, rapid selection of a compensatory mutant suggested conserved mechanisms of lyssavirus assembly and the requirement for only few adaptive mutations to fit the heterogenotypic M to a RABV backbone. Whereas the compensatory mutant replicated to similar infectious titers as RABV M-expressing virus, ultrastructural analysis revealed that both nonadapted EBLV M chimeras and the compensatory mutant differed from RABV M expressing viruses in the lack of intracellular viruslike structures that are enveloped and accumulate in cisterna of the degranulated and dilated rough endoplasmic reticulum compartment. Moreover, all viruses were able to bud at the plasma membrane. Since the lack of the intracellular viruslike structures correlated with the type of M protein but not with the efficiency of virus release, we hypothesize that the M proteins of EBLV-1 and RABV differ in their target membranes for virus assembly. Although the biological function of intracellular assembly and accumulation of viruslike structures in the endoplasmic reticulum remain unclear, the observed differences could contribute to diverse host tropism or pathogenicity.