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Mosquitoes modified to resist dengue may help curb disease transmission
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Researchers have genetically modified Aedes aegypti mosquitoes to resist developing infection from dengue virus by activating a component of the insects’ own immune system in an effort to prevent disease transmission, according to recent study findings published in PLOS Neglected Tropical Diseases.
Although researchers have spent decades trying to control the spread of dengue virus, it still results in approximately 390 million infections each year, George Dimopoulos, PhD, professor in the department of molecular microbiology and immunology and member of the Johns Hopkins Research Institute, and colleagues reported. Because of the lack of treatment options and limited availability of a licensed vaccine, vector control remains a crucial strategy in reducing transmission.
“If you can replace a natural population of dengue-transmitting mosquitoes with genetically modified ones that are resistant to virus, you can stop disease transmission,” Dimopoulos said in a press release. “This is a first step toward that goal.”
Previous studies have shown that mosquitoes use a molecular pathway known as JAK/STAT to fight dengue virus infection. During a recent investigation, Dimopoulos and colleagues evaluated whether manipulating the mosquitoes’ defense system against dengue could increase antiviral activity.
For the study, the mosquitoes’ immune systems were pre-activated with a bloodmeal prior to dengue exposure, which the researchers said is necessary to enhance resistance. After infecting the recently-fed mosquitoes with dengue virus (DENV) type-2, Dimopoulos and colleagues altered the fatbody tissue to overexpress either the Dome or Janus kinase Hop pathway receptors to further activate JAK/STAT. This resulted in a 78.18% reduction in viral copies with overexpression of Dome, and an 83.6% reduction in viral copies with overexpression of Hop in the mosquitoes’ gut compared with wild-type mosquitoes. The researchers also observed a significant reduction in copies within the salivary glands.
Further analyses using DENV type-4 yielded similar results. However, enhanced JAK/STAT activation did not generate stronger immunity against Zika or chikungunya viruses.
“This finding, although disappointing, teaches us something about the mosquito’s immune system and how it deals with different viruses,” Dimopoulos said in the release. “It will guide us on how to make mosquitoes resistant to multiple types of viruses.”
Dimopoulos and colleagues found that the genetically modified mosquitoes had similar lifespans compared with wild-type mosquitoes; however, they produced fewer eggs. In the press release, Dimopoulos acknowledged that there are concerns with releasing them into the wild.
“This is why extensive lab and semi-field studies are required to get it right,” he said. “If scientists can get this to work, however, it could become a very effective way of controlling disease. It could be done without people having to actively participate. They would get long-lasting protection without having to take medication, get vaccinated or use bed nets or repellants.”
They researchers noted that recently developed gene-drive systems could enhance the spread of pathogen resistance in mosquito populations in a “self-propagating fashion, even at a certain fitness cost.” They are working on similar models in Anopheles mosquitoes that transmit malaria, according to the release. – by Stephanie Viguers
Disclosure: The researchers report no relevant financial disclosures.
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