Nav: Home

Researchers create mosquito resistant to dengue virus

January 12, 2017

Researchers from the Johns Hopkins Bloomberg School of Public Health have genetically modified mosquitoes to resist infection from dengue virus, a virus that sickens an estimated 96 million people globally each year and kills more than 20,000, mostly children.

The research, published Jan. 12 in PLOS Neglected Tropical Diseases, shows it is possible, in the lab, to boost the Aedes aegypti mosquito's natural ability to fight the dengue virus as a first step toward suppressing its ability to spread the disease. The findings could be a prelude to developing a strategy to eliminate the threat of dengue. Forty percent of the world's population live in areas where they are at risk of the virus, which is most common in Southeast Asia and the western Pacific islands and has been rapidly increasing in Latin America and the Caribbean.

"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," says study leader George Dimopoulos, PhD, a professor in the Department of Molecular Microbiology and Immunology and a member of the Johns Hopkins Malaria Research Institute. "This is a first step toward that goal."

While the new mosquitoes significantly suppressed dengue virus infection they did not show any resistance to Zika or chikungunya, two other viruses carried by Aedes aegypti. "This finding, although disappointing, teaches us something about the mosquito's immune system and how it deals with different viruses. It will guide us on how to make mosquitoes resistant to multiple types of viruses" he says. While being resistant to one disease is a good start, "ideally, you want a mosquito that is resistant to other viruses as well," he says.

Mosquitoes acquire viruses by feeding on the blood of humans who are sickened with them. Once the mosquitoes are infected, they bite other healthy humans and pass the disease along to them. Many efforts are underway to figure out how to break that cycle, and most scientists agree that the use of multiple methods will be required to eliminate dengue and other mosquito-borne diseases.

Researchers say that Aedes aegypti mosquitoes do mount an immune system response when exposed to the dengue virus, but it appears to be too weak to stop transmission. Knowing this, Dimopoulos and his colleagues were able to manipulate a component of the immune system, the JAK-STAT pathway, that regulates production of antiviral factors. They did this in a part of the mosquito known as the fat body, its version of the liver. Notably, the JAK-STAT pathway is involved in antiviral activity in humans as well.

The genetic modification resulted in fewer mosquitoes becoming infected, and most of those that did had very low levels of dengue virus in their salivary glands, the location from which it gets transmitted to humans. These experiments, however, didn't lower the level of virus in all mosquitoes to zero, something that puzzled the scientists. They say more research is needed to understand whether this level of virus suppression would be enough to halt disease transmission, and they are working on other experiments to see if they can produce antiviral factors in the gut, which could assist in inducing a stronger immune response and possibly confer resistance to the other viruses.

The researchers found that the dengue-resistant mosquitoes live as long as the wild mosquitoes, though they do produce fewer eggs, most likely because the same mechanism involved in dialing up the immune system to fight dengue also plays a role in egg production.

"It's likely if we turn this on in the gut we could have a much stronger effect, without compromising egg production," Dimopoulos says.

Once genetically modified mosquitoes resistant to dengue are developed, scientists would test them in large field cages to see how they compete with wild mosquitoes in very controlled experiments.

The best way to ensure that the genetically modified mosquitoes become the dominant type is for researchers to add something known as a "gene drive" to the new mosquitoes. This essentially makes them genetically superior mosquitoes by ensuring that all offspring of wild- type and genetically modified mosquitoes will be disease resistant.

"In this way, you could convert a disease-transmitting mosquito population to one that does not transmit disease," Dimopoulos says.

Scientists acknowledge there are concerns with the release of genetically modified mosquitoes in the environment since they can't be recaptured. They are there to stay.

"This is why extensive lab and semi-field studies are required to get it right," he says. If the 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.

Dimopoulos and other researchers are working on similar models in Anopheles mosquitoes which carry the parasite that causes malaria.

The entire process of developing and introducing disease-resistant mosquitoes into the wild could take a decade or more.
-end-
"Engineered Aedes aegypti JAK/STAT pathway-mediated immunity to dengue virus" was written by Natapong Jupatanakul; Shuzhen Sim; Yesseinia I. Angleró-Rodríguez; Jayme Souza-Neto; Suchismita Das; Kristin E. Poti; Shannan L. Rossi; Nicholas Bergren; Nikos Vasilakis; and George Dimopoulos.

The study was funded by the National Institutes of Health's National Institute of Allergy and Infectious Diseases (RO1AI101431, R21AI090188 and 1R24AI120942).

Johns Hopkins University Bloomberg School of Public Health

Related Immune System Articles:

Immune system upgrade
Theoretically, our immune system could detect and kill cancer cells.
Using the immune system as a defence against cancer
Research published today in the British Journal of Cancer has found that a naturally occurring molecule and a component of the immune system that can successfully target and kill cancer cells, can also encourage immunity against cancer resurgence.
First impressions go a long way in the immune system
An algorithm that predicts the immune response to a pathogen could lead to early diagnosis for such diseases as tuberculosis
Filming how our immune system kill bacteria
To kill bacteria in the blood, our immune system relies on nanomachines that can open deadly holes in their targets.
Putting the break on our immune system's response
Researchers have discovered how a tiny molecule known as miR-132 acts as a 'handbrake' on our immune system -- helping us fight infection.
Decoding the human immune system
For the first time ever, researchers are comprehensively sequencing the human immune system, which is billions of times larger than the human genome.
Masterswitch discovered in body's immune system
Scientists have discovered a critical part of the body's immune system with potentially major implications for the treatment of some of the most devastating diseases affecting humans.
How a fungus can cripple the immune system
An international research team led by Professor Oliver Werz of Friedrich Schiller University, Jena, has now discovered how the fungus knocks out the immune defenses, enabling a potentially fatal fungal infection to develop.
How the immune system protects us against bowel cancer
Researchers from Charité - Universitätsmedizin Berlin have discovered a protective mechanism which is used by the body to protect intestinal stem cells from turning cancerous.
How herpesviruses shape the immune system
DZIF scientists at the Helmholtz Zentrum München have developed an analytic method that can very precisely detect viral infections using immune responses.
More Immune System News and Immune System Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

In & Out Of Love
We think of love as a mysterious, unknowable force. Something that happens to us. But what if we could control it? This hour, TED speakers on whether we can decide to fall in — and out of — love. Guests include writer Mandy Len Catron, biological anthropologist Helen Fisher, musician Dessa, One Love CEO Katie Hood, and psychologist Guy Winch.
Now Playing: Science for the People

#541 Wayfinding
These days when we want to know where we are or how to get where we want to go, most of us will pull out a smart phone with a built-in GPS and map app. Some of us old timers might still use an old school paper map from time to time. But we didn't always used to lean so heavily on maps and technology, and in some remote places of the world some people still navigate and wayfind their way without the aid of these tools... and in some cases do better without them. This week, host Rachelle Saunders...
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.