Identification of viral genomic elements responsible for rabies virus neuroinvasiveness
Identification of viral genomic elements responsible for rabies virus neuroinvasiveness
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DOI：
10.1073/pnas.0407289101
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发表时间：
2004-11-16
影响因子：
11.1
通讯作者：
Dietzschold, B
中科院分区：
文献类型：
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作者：
Faber, M;Pulmanausahakul, R;Dietzschold, B
减毒的组织培养适应性狂犬病病毒（RV）毒株和天然街头狂犬病病毒（RV）毒株在神经侵袭性方面存在很大差异。为了鉴定RV从外周部位进入CNS并引起致命神经系统疾病的能力的元件，我们构建了银发蝙蝠相关RV（SHBRV）菌株18的全长cDNA克隆，并将编码RV蛋白的基因和该高度神经侵袭性RV菌株的基因组序列与高度减毒的非神经侵袭性RV疫苗株（SN 0）的基因组序列交换。对从SHBRV-18 cDNA中回收的重组RV（SB 0）的分析表明，该RV与WT SHBRV-18在表型上无法区分。嵌合病毒的表征表明，除了RV糖蛋白，这在RV从外周部位侵入CNS的能力中起着主要作用，病毒元素，如尾部序列，RV聚合酶和假基因有助于RV神经侵袭。分析还显示，RV的神经侵袭性与RV病毒粒子内化所需的时间和病毒在神经母细胞瘤细胞中生长的能力呈负相关。
Attenuated tissue culture-adapted and natural street rabies virus (RV) strains differ greatly in their neuroinvasiveness. To identify the elements responsible for the ability of an RV to enter the CNS from a peripheral site and to cause lethal neurological disease, we constructed a full-length cDNA clone of silver-haired bat-associated RV (SHBRV) strain 18 and exchanged the genes encoding RV proteins and genomic sequences of this highly neuroinvasive RV strain with those of a highly attenuated nonneuroinvasive RV vaccine strain (SN0). Analysis of the recombinant RV (SB0), which was recovered from SHBRV-18 cDNA, indicated that this RV is phenotypically indistinguishable from WT SHBRV-18. Characterization of the chimeric viruses revealed that in addition to the RV glycoprotein, which plays a predominant role in the ability of an RV to invade the CNS from a peripheral site, viral elements such as the trailer sequence, the RV polymerase, and the pseudogene contribute to RV neuroinvasiveness. Analyses also revealed that neuroinvasiveness of an RV correlates inversely with the time necessary for internalization of RV virions and with the capacity of the virus to grow in neuroblastoma cells.