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Human cytomegalovirus immediate-early-gene expression disrupts embryogenesis in transgenic Drosophila

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Abstract

Intrauterine infection with human cytomegalovirus (HCMV) is the leading viral cause of birth defects involving the central nervous system. Due to the highly species specific nature of the virus, its course of natural infection cannot be studied in animal models. Here we introduce a novel transgenic Drosophila model system for studying the effects of the major viral regulatory genes, the immediate-early genes, on normal embryonic development. We show that ectopic expression of the immediate-early genes in Drosophila led to increased embryonic lethality manifested in disintegration of the embryos. Further analysis suggested that immediate-early gene expression interfered with adherens junction maintenance, leading to the disruption of embryonic epithelial integrity. Owing to the evolutionary conservation of developmental mechanisms from invertebrates to mammals, we anticipate that the studies in Drosophila will be relevant also to humans and will ultimately provide a versatile system for studying different aspects of viral-host interactions.

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Acknowledgements

We thank Hava Haikin, Virology Department at Soroka Mediacl Center, Israel, for HCMV infected cells; Alain Debec, Gavdos group, France, for the GFP trap line; Dr. John Belote, Syracuse University, USA, for transgenic line harboring an Hsp70-GFP construct; Inbal Bulukan for help with embryo injections. This work was supported in part by a grant from the ‘Israel Ministry of Health’ to F.S.N-S and by an institutional award to F.S.N-S.

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Correspondence to Shira Neuman-Silberberg.

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Steinberg, R., Shemer-Avni, Y., Adler, N. et al. Human cytomegalovirus immediate-early-gene expression disrupts embryogenesis in transgenic Drosophila . Transgenic Res 17, 105–119 (2008). https://doi.org/10.1007/s11248-007-9136-5

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Keywords

  • HCMV
  • Immediate early
  • Birth defects
  • Drosophila model
  • Adhesion