Summer 2007
NIAID Discovery News
Modified Skeeters Could Save People from Dengue Fever
Dengue’s common name, break bone fever, speaks of the misery caused by this mosquito-borne illness. Annually, about 100 million people worldwide are stricken with fever, headache, and "bone-breaking" joint pain characteristic of dengue, and more than 20,000 die of its most severe form.
Dengue cases can be reduced through mosquito control techniques such as eliminating mosquito breeding sites and applying pesticides, but these efforts alone cannot completely break the cycle of disease, notes NIAID grantee Carol Blair, Ph.D., of Colorado State University (CSU). Breaking the cycle of disease, she says, requires either creating a vaccine against dengue virus, which has proved difficult, or finding a way to keep mosquitoes from becoming infected in the first place.
Dr. Blair and her colleagues, including Ken Olson, Ph.D., of CSU, and Anthony James, Ph.D., of the University of California, Irvine, began their attempts to build a dengue-resistant mosquito more than a decade ago, soon after the discovery of RNA interference (RNAi). RNAi is viral defense mechanism known to occur in plants, insects, and higher animals as well. To harness RNAi’s potential to make dengue-resistant mosquitoes, the scientists had to clear three hurdles: get RNAi to work at the right time (immediately after the insects become infected), in the right place (midgut cells), and in the right amount (quantities of a naturally occurring double-stranded form of viral RNA had to be boosted to allow mosquitoes to develop significant resistance to dengue infection.)
Recently, they succeeded. Steady-handed researchers injected thousands of mosquito eggs with cloned dengue virus genes that had been manipulated to trigger RNAi at the right time, place, and amount. The resulting genetically modified mosquitoes not only were highly resistant to dengue virus infection, they also appeared to pass this characteristic on to succeeding generations.
Dr. Blair and her colleagues are continuing their efforts to build dengue-resistant mosquitoes by developing a better understanding of how dengue virus evades the destructive effects of RNAi in wild mosquitoes. Dr. Blair says the ongoing research will benefit from the newly available genomic sequence of Aedes aegypti, the mosquito species that carries both dengue and yellow fever viruses, a recent advance also supported by NIAID.
—Anne A. Oplinger
References
Fanz, A. W. E. et al. Engineering RNA interference-based resistance to dengue virus type 2 in genetically modified Aedes aegypti. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.0600479103 (2006).
Nene, V. et al. Genome sequence of Aedes aegypti, a major arbovirus vector. Science DOI: 10.1126/science.1138878. (published online May 17, 2007).
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