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Introduction of the Six Major Genomic Deletions of Modified Vaccinia Virus Ankara (MVA) into the Parental Vaccinia Virus Is Not Sufficient To Reproduce an MVA-Like Phenotype in Cell Culture and in Mice

  • Meisinger-Henschel, Christine Bavarian Nordic GmbH, Fraunhoferstrasse 13, 82152 Martinsried, Germany
  • Späth, Michaela Bavarian Nordic GmbH, Fraunhoferstrasse 13, 82152 Martinsried, Germany
  • Lukassen, Susanne Bavarian Nordic GmbH, Fraunhoferstrasse 13, 82152 Martinsried, Germany
  • Wolferstätter, Michael Bavarian Nordic GmbH, Fraunhoferstrasse 13, 82152 Martinsried, Germany
  • Kachelriess, Heike Bavarian Nordic GmbH, Fraunhoferstrasse 13, 82152 Martinsried, Germany
  • Baur, Karen Bavarian Nordic GmbH, Fraunhoferstrasse 13, 82152 Martinsried, Germany
  • Dirmeier, Ulrike Bavarian Nordic GmbH, Fraunhoferstrasse 13, 82152 Martinsried, Germany
  • Wagner, Markus Bavarian Nordic GmbH, Fraunhoferstrasse 13, 82152 Martinsried, Germany
  • Chaplin, Paul Bavarian Nordic GmbH, Fraunhoferstrasse 13, 82152 Martinsried, Germany
  • Suter, Mark University of Zurich, Dekanat Vetsuisse Faculty, Winterthurerstrasse 266a, 8057 Zürich, Switzerland
  • Hausmann, Jürgen Bavarian Nordic GmbH, Fraunhoferstrasse 13, 82152 Martinsried, Germany
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Published in:
  • Journal of Virology. - American Society for Microbiology. - 2010, vol. 84, no. 19, p. 9907-9919
Immunology
Insect Science
Microbiology
Virology
English ABSTRACT
Modified vaccinia virus Ankara (MVA) has a highly restricted host range in cell culture and is apathogenic in vivo. MVA was derived from the parental chorioallantois vaccinia virus Ankara (CVA) by more than 570 passages in chicken embryo fibroblast (CEF) cells. During CEF cell passaging, six major deletions comprising 24,668 nucleotides occurred in the CVA genome. We have cloned both the MVA and the parental CVA genome as bacterial artificial chromosomes (BACs) and have sequentially introduced the six major MVA deletions into the cloned CVA genome. Reconstituted mutant CVA viruses containing up to six major MVA deletions showed no detectable replication restriction in 12 of 14 mammalian cell lines tested; the exceptions were rabbit cell lines RK13 and SIRC. In mice, CVA mutants with up to three deletions showed slightly enhanced virulence, suggesting that gene deletion in replicating vaccinia virus (VACV) can result in gain of fitness in vivo. CVA mutants containing five or all six deletions were still pathogenic, with a moderate degree of attenuation. Deletion V was mainly responsible for the attenuated phenotype of these mutants. In conclusion, loss or truncation of all 31 open reading frames in the six major deletions is not sufficient to reproduce the specific MVA phenotype of strong attenuation and highly restricted host range. Mutations in viral genes outside or in association with the six major deletions appear to contribute significantly to this phenotype. Host range restriction and avirulence of MVA are most likely a cooperative effect of gene deletions and mutations involving the major deletions.
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  • English
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bronze
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https://sonar.ch/global/documents/204090
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