Etingov Igor, Itah Refael, Mincberg Michal, Keren-Naus Ayelet, Nam Hyun-Joo, Agbandje-McKenna Mavis, Davis Claytus
Department of Virology and Developmental Molecular Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Virology. 2008 Sep 30;379(2):245-55. doi: 10.1016/j.virol.2008.06.042. Epub 2008 Aug 5.
Well-defined tissue tropism makes Autonomous Parvoviruses a valuable model for studies of virus-cell interactions and gene therapy research. We developed a new Minute Virus of Mice variant, different from the known prototype (MVMp) and immunosuppressive (MVMi) strains. The new virus variant, designated F1, was isolated from the culture of semi-permissive Fisher Rat Fibroblasts, F111, infected with MVMp. The F1 genome carried point mutations in regions known to determine the mutually restricted host ranges of MVMp and MVMi. In F111 cells, F1 cytotoxicity, gene expression and multiplication were significantly higher compared to MVMp. Conversely the wild-type virus propagated in MVMp-permissive cells more efficiently than the F1. Reversion of the F1-specific mutations to wild-type MVMp sequence, following reverse-passaging of the mutant virus in MVMp-permissive cells, confirmed a specific adaptation of the F1 virus to F111 cells. Considerable divergence in tissue specificities between the wild-type and mutant viruses was demonstrated in vivo.
明确的组织嗜性使自主细小病毒成为研究病毒 - 细胞相互作用和基因治疗研究的有价值模型。我们开发了一种新的小鼠微小病毒变体,它不同于已知的原型(MVMp)和免疫抑制(MVMi)毒株。这种新的病毒变体命名为F1,是从用MVMp感染的半允许性Fisher大鼠成纤维细胞F111的培养物中分离出来的。F1基因组在已知决定MVMp和MVMi相互限制宿主范围的区域携带点突变。在F111细胞中,与MVMp相比,F1的细胞毒性、基因表达和增殖显著更高。相反,野生型病毒在MVMp允许的细胞中比F1更有效地繁殖。在MVMp允许的细胞中对突变病毒进行反向传代后,F1特异性突变回复到野生型MVMp序列,证实了F1病毒对F111细胞的特异性适应。在体内证明了野生型和突变病毒之间组织特异性的显著差异。