Human cytomegalovirus immediate-early-gene expression disrupts embryogenesis in transgenic Drosophila.
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.
Steinberg
Racheli
R
Virology and Developmental Genetics/Health Sciences, Ben-Gurion University of the Negev, POB 653, Beer-Sheva 84105, Israel.
Shemer-Avni
Yonat
Y
Adler
Noa
N
Neuman-Silberberg
Shira
S
D022005:Adherens Junctions / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology; D000818:Animals; D030801:Animals, Genetically Modified; D051186:Armadillo Domain Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D003587:Cytomegalovirus / Q000235:genetics* / Q000472:pathogenicity*; D003586:Cytomegalovirus Infections / Q000196:embryology / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D004330:Drosophila / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D017781:Genes, Immediate-Early; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; D017931:DNA Primers; D004279:DNA, Viral; D029721:Drosophila Proteins; D014157:Transcription Factors