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Identification and Characterization of Metastatic Factors by Gene Transfer into the Novel RIP-Tag; RIP-tva Murine Model
Published on: October 16, 2017
An extension of the Minute Virus of Mice tissue tropism
Igor Etingov1, Refael Itah, Michal Mincberg
1Department of Virology and Developmental Molecular Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel. etingov@bgu.ac.il
Abstract:
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.
Insights
Researchers engineered a novel Minute Virus of Mice (MVM) variant, F1, which shows enhanced replication in specific rat cells. This MVM variant exhibits altered tissue tropism in vivo, offering new insights into parvovirus adaptation and host interactions.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Autonomous Parvoviruses, like Minute Virus of Mice (MVM), are valuable models for virus-cell interactions and gene therapy due to their specific tissue tropism.
- Existing MVM strains include the prototype (MVMp) and immunosuppressive (MVMi) variants, each with distinct host range characteristics.
Purpose of the Study:
- To develop and characterize a new MVM variant with altered host range and tissue tropism.
- To investigate the genetic basis for MVM adaptation to semi-permissive cell lines.
Main Methods:
- Isolation of a novel MVM variant (F1) from infected Fisher Rat Fibroblasts (F111) with MVMp.
- Genomic analysis of F1 to identify point mutations in host range-determining regions.
- Comparative analysis of F1 and MVMp replication, cytotoxicity, and gene expression in F111 and MVMp-permissive cells.
- In vivo studies to assess tissue tropism divergence.
Main Results:
- The F1 variant demonstrated significantly higher cytotoxicity, gene expression, and multiplication in F111 cells compared to MVMp.
- MVMp propagated more efficiently than F1 in MVMp-permissive cells.
- Reverse-passaging confirmed F1's adaptation to F111 cells through reversion of specific mutations.
- In vivo experiments revealed considerable divergence in tissue specificities between F1 and wild-type MVM.
Conclusions:
- The novel F1 MVM variant exhibits specific adaptation to semi-permissive rat fibroblasts (F111).
- Genetic mutations in F1 are responsible for its altered host range and enhanced replication in F111 cells.
- The F1 variant displays distinct in vivo tissue tropism compared to wild-type MVM, highlighting the plasticity of parvovirus adaptation.

