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Genetically Modified Mosquitoes Impede Dengue Transmission

Bugged by the idea of genetically modified mosquitoes?

You’re not alone. Even at the height of the Zika outbreak in Miami last summer, many residents there expressed concerns over the long-term environmental and public health implications associated with their release.

However, in spite of these objections, they remain an important weapon in the still-developing armamentarium—such as it is—against vector-borne diseases. Now, a new study, published January 12, 2017 in the journal PLOS Neglected Tropical Diseases supports their efficacy in controlling at least one such disease: Dengue.

The authors of the study, from the Johns Hopkins Bloomberg School of Public Health, showed that it is possible to bolster the immunity of the Aedes aegypti mosquito, the species that transmits Dengue, Zika, and Chikungunya, against these viruses and effectively suppress its ability to transmit the disease.

If left alone, the immune response of the Aedes aegypti to Dengue is believed to be too weak to stop infection and, ultimately, transmission. However, the Johns Hopkins team found that by manipulating the JAK-STAT pathway in the mosquitoes’ immune system, they were able to reduce the number of insects infected with the virus; even among those mosquitoes that became infected following their intervention, levels of viral RNA were low and present only in the salivary glands.

They accomplished this through the activation of the conserved antiviral JAK/STAT pathway in the mosquitoes’ fat body tissue (analogous to the human liver) by “overexpressing either the receptor Dome or the Janus kinase Hop” via the blood feeding-induced vitellogenin promoter (mosquitoes acquire and transmit viruses such as Dengue through blood-feeding). Notably, the Dengue-resistant mosquitoes live as long as naturally occurring mosquitoes, even though they produce fewer eggs, likely as a result of the genetic modification.

“[Our results show that] the mosquitoe’s innate immune system can be manipulated to confer resistance to Dengue virus,” study co-author George Dimopoulos, PhD, MBA, a professor in the Department of Molecular Microbiology and Immunology at Bloomberg School of Public Health told ContagionTM. “And, the manipulation did not have a strong fitness effect on the mosquito.”

Of course, the JAK-STAT pathway is also involved in human immune response, but this type of genetic modification in humans is likely far off into the future. Indeed, Dr. Dimopoulos and his colleagues were disappointed to find out that their modification of the pathway did not protect the mosquitoes from the Zika virus or Chikungunya, although they are optimistic that they will find solutions to this puzzle as their research continues.

“We believe that our data suggest that the Zika and Chikungunya viruses may be targeted by this same immune pathway more effectively in a different tissue like the mosquito intestine, and the study guides our future experiments to investigate this,” Dr. Dimopoulos said.

And for those concerned about the safety of such genetic experiments? “We have manipulated the mosquitoes in a way that they will not express any foreign genes with unforeseeable effects,” he explained. “Both Hop and Dome transgenes that are overexpressed in the genetically modified mosquitoes are the mosquito’s own genes, thereby not altering the biology of the insect in any fundamental way, other than providing it with a more effective immune system.”
Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.
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