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Entry is a rate-limiting step for viral infection in a Drosophila melanogaster model of pathogenesis

Nature Immunology volume 5, pages 81–87 (2004)Cite this article

Abstract

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.

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Figure 1: DCV is infectious in vitro.
Figure 2: DCV traffics through a vesicular compartment and requires a functional endocytic apparatus in vitro.
Figure 3: Clathrin-mediated endocytosis is required for DCV infection.
Figure 4: Autonomous requirement for dynamin in viral entry.

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Acknowledgements

We thank P. Christian for viral reagents, and members of the Perrimon lab, M. Gonzalez-Gaitan, J.T. Littleton, J.-M. Reichhart and T. Schwarz for fly strains. We thank M. Tudor for statistical analysis and discussions, and H. Ploegh, C. Roman, B. Stronach, E. Selva, L. van Parijs and S. Whelan for discussions and for critically reading the manuscript. We thank J. Kopinja and C. Villalta for injections, and S. Armknecht, and L. Hrdlicka for technical assistance. Supported by a National Institutes of Health National Research Service Award (S.C.) and RO1-AI051365-01A1.

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  1. Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Sara Cherry & Norbert Perrimon

  2. Howard Hughes Medical Institute, 200 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Norbert Perrimon

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Correspondence to Sara Cherry.

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Cherry, S., Perrimon, N. Entry is a rate-limiting step for viral infection in a Drosophila melanogaster model of pathogenesis. Nat Immunol 5, 81–87 (2004). https://doi.org/10.1038/ni1019

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