Entry is a rate-limiting step for viral infection in a Drosophila melanogaster model of pathogenesis.
The identification of host factors that control susceptibility to infection has been hampered by a lack of amenable genetic systems. We established an in vivo model to determine the host factors that control pathogenesis and identified viral entry as a rate-limiting step for infection. We infected Drosophila melanogaster cells and adults with drosophila C virus and found that the clathrin-mediated endocytotic pathway is essential for both infection and pathogenesis. Heterozygosity for mutations in genes involved in endocytosis is sufficient to protect flies from pathogenicity, indicating the exquisite sensitivity and dependency of the virus on this pathway. Thus, this virus model provides a sensitive and efficient approach for identifying components required for pathogenesis.
Cherry
Sara
S
Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA. scherry@genetics.med.harvard.edu
Perrimon
Norbert
N
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002966:Clathrin / Q000276:immunology; D003588:Cytopathogenic Effect, Viral; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000276:immunology* / Q000821:virology*; D034281:Dynamins / Q000276:immunology; D004705:Endocytosis / Q000276:immunology; D007304:Insect Viruses / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D008856:Microscopy, Fluorescence; D010849:Picornaviridae / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D010850:Picornaviridae Infections / Q000276:immunology* / Q000821:virology
D002966:Clathrin; D034281:Dynamins