Abstract
The innate immune response of Drosophila melanogaster is governed by a complex set of signaling pathways that trigger antimicrobial peptide (AMP) production, phagocytosis, melanization, and encapsulation. Although immune responses against both bacteria and fungi have been demonstrated in Drosophila , identification of an antiviral response has yet to be found. To investigate what responses Drosophila mounts against a viral infection, we have developed an in vivo Drosophila X virus (DXV)-based screening system that identifies altered sensitivity to viral infection by using DXV's anoxia-induced death pathology. Using this system to screen flies with mutations in genes with known or suggested immune activity, we identified the Toll pathway as a vital part of the Drosophila antiviral response. Inactivation of this pathway instigated a rapid onset of anoxia induced death in infected flies and increases in viral titers compared to those in WT flies. Although constitutive activation of the pathway resulted in similar rapid onset of anoxia sensitivity, it also resulted in decreased viral titer. Additionally, AMP genes were induced in response to viral infection similar to levels observed during Escherichia coli infection. However, enhanced expression of single AMPs did not alter resistance to viral infection or viral titer levels, suggesting that the main antiviral response is cellular rather than humoral. Our results show that the Toll pathway is required for efficient inhibition of DXV replication in Drosophila . Additionally, our results demonstrate the validity of using a genetic approach to identify genes and pathways used in viral innate immune responses in Drosophila.
References
47
Referenced
342
10.1016/S0952-7915(97)80152-5
10.1038/35021228
10.1038/90609
10.1016/S0952-7915(02)00013-4
10.1038/nature01991
10.1073/pnas.221458698
- Rizki T. M. (1978) in The Genetics and Biology of Drosophila eds. Ashburner M. & Wright T. R. F. (Academic New York) pp. 561-599.
-
Rizki T. M. & Rizki R. M. (1984) in Insect Ultrastrucure eds. King R. C. & Akai H. H. (Plenum New York) pp. 579-604.
(
10.1007/978-1-4613-2715-8_16
) 10.1038/ni1123
10.1038/nature02021
10.1038/ni955
10.1016/S0092-8674(00)80172-5
10.1016/0092-8674(93)90495-C
10.1146/annurev.ge.29.120195.002103
- Qiu, P., Pan, P. C. & Govind, S. (1998) Development (Cambridge, U.K.) 125, 1909-1920. / Development (Cambridge, U.K.) (1998)
10.1016/S1074-7613(04)00104-9
10.1016/S1534-5807(01)00059-4
10.1016/S1074-7613(02)00454-5
10.1074/jbc.C000341200
10.1073/pnas.1035902100
10.1101/gad.856901
10.1038/79801
10.1101/gad.817800
10.1101/gad.203301
10.1101/gad.13.7.792
10.1016/S1074-7613(00)80208-3
10.1038/ni747
10.1038/ni1019
10.1006/viro.1996.0610
10.1099/0022-1317-42-2-241
- Harlow E. & Lane D. (1999) in Using Antibodies eds. Cuddihy J. & Kuhlman T. (Cold Spring Harbor Lab. Press Plainview NY).
10.1073/pnas.042411999
10.1039/an9931800401
10.1016/S1471-4906(01)01887-7
10.1093/emboj/21.11.2568
10.1073/pnas.261573998
10.1016/S0145-305X(99)00015-4
- Meister, M., Hetru, C. & Hoffmann, J. A. (2000) Curr. Topics Microbiol. Immunol. 248, 17-36. / Curr. Topics Microbiol. Immunol. (2000)
10.1073/pnas.97.7.3376
10.1073/pnas.95.24.14337
10.1016/S0960-9822(00)00569-8
10.1126/science.284.5422.1991
10.1128/JVI.75.2.996-1003.2001
10.1101/gad.1022802
10.1038/76032
10.1038/12984
10.1126/science.275.5299.536
Dates
Type | When |
---|---|
Created | 20 years, 3 months ago (May 6, 2005, 8:30 p.m.) |
Deposited | 3 years, 4 months ago (April 12, 2022, 2:32 p.m.) |
Indexed | 1 week, 2 days ago (Aug. 26, 2025, 2:30 a.m.) |
Issued | 20 years, 3 months ago (May 6, 2005) |
Published | 20 years, 3 months ago (May 6, 2005) |
Published Online | 20 years, 3 months ago (May 6, 2005) |
Published Print | 20 years, 3 months ago (May 17, 2005) |
@article{Zambon_2005, title={The Toll pathway is important for an antiviral response in Drosophila}, volume={102}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0409181102}, DOI={10.1073/pnas.0409181102}, number={20}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Zambon, Robert A. and Nandakumar, Madhumitha and Vakharia, Vikram N. and Wu, Louisa P.}, year={2005}, month=may, pages={7257–7262} }