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An evolutionary conserved function of the JAK-STAT pathway in anti-dengue defense
Open accessAbstract
Here, we show that the major mosquito vector for dengue virus uses the JAK-STAT pathway to control virus infection. Dengue virus infection in Aedes aegypti mosquitoes activates the JAK-STAT immune signaling pathway. The mosquito's susceptibility to dengue virus infection increases when the JAK-STAT pathway is suppressed through RNAi depletion of its receptor Domeless (Dome) and the Janus kinase (Hop), whereas mosquitoes become more resistant to the virus when the negative regulator of the JAK-STAT pathway, PIAS, is silenced. The JAK-STAT pathway exerts its anti-dengue activity presumably through one or several STAT-regulated effectors. We have identified, and partially characterized, two JAK-STAT pathway-regulated and infection-responsive dengue virus restriction factors (DVRFs) that contain putative STAT-binding sites in their promoter regions. Our data suggest that the JAK-STAT pathway is part of the A. aegypti mosquito's anti-dengue defense and may act independently of the Toll pathway and the RNAi-mediated antiviral defenses.
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Cited by
Biochemistry and Molecular Biology of Flaviviruses
Barrows, N. J., Campos, R. K., Liao, K.-C., Prasanth, K. R., Soto-Acosta, R., Yeh, S.-C., Schott-Lerner, G., Pompon, J., Sessions, O. M., Bradrick, S. S., et al. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00719 · Cited by 341
Paradkar, P. N., Trinidad, L., Voysey, R., Duchemin, J.-B., & Walker, P. J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1205231109 · Cited by 329
Hoang, L. T., Lynn, D. J., Henn, M., Birren, B. W., Lennon, N. J., Le, P. T., Duong, K. T. H., Nguyen, T. T. H., Mai, L. N., Farrar, J. J., et al. (2010) · Journal of Virology · doi:10.1128/jvi.01224-10 · Cited by 137
Alton, L. A., Novelo, M., Beaman, J. E., Arnold, P. A., Bywater, C. L., Kerton, E. J., Lombardi, E. J., Koh, C., & McGraw, E. A. (2023) · Global Change Biology · doi:10.1111/gcb.16906 · Cited by 6
Martin, L. E., Barr, J. S., Cartailler, J.-P., Shrestha, S., Estévez-Lao, T. Y., & Hillyer, J. F. (2025) · Immunity & Ageing · doi:10.1186/s12979-025-00551-7 · Cited by 3
Metadata
- Authors
- Souza-Neto, J. A., Sim, S., & Dimopoulos, G.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2009-10-20
- Volume
- 106
- Issue
- 42
- Pages
- 17841-17846
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2079936712
- Cited by
- 573
- References
- 0
- FWCI
- 8.78
- Type
- journal article
- Language
- en
- Open access
- green
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- Souza-Neto, J. A., Sim, S., & Dimopoulos, G. (2009). An evolutionary conserved function of the JAK-STAT pathway in anti-dengue defense. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0905006106
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