What’s in a mosquito bite? For some, it means an itchy red welt. For others, it means the shivering, fever, headaches, vomiting, seizures, and even death associated with malaria.
Malaria is a vector-borne disease, which means it is spread by an organism, usually an insect, that feeds on the blood of an infected person or animal and then bites a healthy person. Yellow fever, dengue fever, chikungunya, lyme disease, African sleeping sickness, and a swarm of other health issues are all transmitted this way.
Scientists in Virginia Tech’s Vector-borne Disease Research Group, formed in 2005 and supported by the Fralin Life Science Institute, make discoveries that protect human health. They have molecularly characterized crucial components of disease-vector transmission and uncovered new information about the genetic ancestry of mosquitoes. These discoveries and the laboratory techniques developed to probe them have changed the way disease transmission is viewed across the world.
“We have assembled a great deal of talent to rid the world of this dangerous health problem,” said Dennis Dean, director of the Fralin Life Science Institute and Virginia Bioinformatics Institute. “We can share the planet with mosquitoes, but they’ve got to keep diseases to themselves.”
Most of the scientists in the group work with mosquitoes. Not all mosquito species transmit disease, and only females bite because they need blood to produce eggs. Males feed on nectar.
Why are mosquito-borne diseases flourishing? In the case of the La Crosse encephalitis virus, entomologist Sally Paulson said she suspects the invasion of an exotic vector species into the United States is to blame. She and biological sciences colleague Dana Hawley seek to understand where and how the disease is occurring and what environmental conditions allow for it.
Mosquitoes adapt to new environments quickly. Entomologist Igor Sharakhov’s research suggests that chromosomes in the mosquito genome change to allow it to adapt and continue to transmit disease.
In 2012, Sharakhov successfully reconstructed the chromosomal evolutionary history for the African Anopheles gambiae mosquito species complex. In a paper published in PLoS Pathogens, he confirmed that several key traits, including the ability to transmit malaria parasites and tolerate brackish breeding sites, have evolved independently several times in this complex. Additionally, the paper showed that a chromosomal arrangement long thought to be derived in malaria vectors is actually the ancestral form. These results significantly alter current understanding of the evolution of medically important traits.
In 2013, research scientists Maria Sharakhova and Igor Sharakhov developed a master map of the Aedes agypti mosquito’s genome that allows scientists to view the locale of genes contributing to the trait of dengue transmission.
“We are working to understand the molecular basis of these chromosomal changes,” Sharakhov said. A better understanding of what’s driving variability could lead scientists to develop counteractive tools.
The aggressive, adaptive nature of the disease parasite also is to blame. Michael Klemba studies how the malaria parasite is able to consume its human host from the inside, devouring most of the red blood cell’s oxygen-carrying protein, hemoglobin.
Biochemist Maria Belen Cassera investigates metabolic pathways in the same parasite to find drug targets.
“The key is targeting a pathway that is not also present in the human body and, therefore, safe for the host,” Cassera said. Also a member of the Center for Drug Discovery, she is involved in a project that screens compounds for malaria drug potential.
Scientists are also working to perfect human-safe insecticides for mosquito nets. Chemist Paul Carlier, also a member of the Center for Drug Discovery, is working with protein expert Jianyong Li to identify insecticidal compounds that could last five to 10 years.
“Mosquitoes are constantly gaining resistance to insecticides,” Carlier said. “We need new active ingredients for insecticide-treated nets.”
Entomologist Troy Anderson is studying insecticide resistance mechanisms to improve the target-site delivery of insecticidal compounds.
In 2012, Anderson, Paulson, Carlier, Li, and colleague Jeffrey Bloomquist, a former Virginia Tech researcher now at the University of Florida, discovered new compounds that were highly active against malaria in the Anopheles gambiae mosquito. In a separate study, this same group identified compounds that increased selectivity for the mosquito over the human enzyme. These modifications can be incorporated into newer chemical designs that should be safer to use for treated bed nets or indoor residual spraying.
The following are the major diseases spread by mosquitoes:
Scientists have turned to genetics to control vector-borne disease. One approach is to knock out the genes that allow the mosquito to transmit disease.
To test this approach, entomologists Kevin Myles and Zach Adelman inject genetic material into mosquito embryos. They used a gene disruption technique to change the eye color of a mosquito, marking the first time scientists successfully edited the genome of a disease vector. Ultimately, they want to apply the technology to engineer disease-resistant mosquitoes.
Molecular biologist Zhijian Tu investigates how a disease-resistant gene travels by tying the gene to a genetic element that spreads itself into mosquito populations. He also examines how a sex-determinant gene on the Y chromosome could be manipulated to control mosquito populations by selectively reducing blood-sucking females.
Another approach is to inhibit mosquito egg production, a focus of biochemist Jinsong Zhu. “Understanding how mosquito endogenous hormones exert their function will facilitate discovery of new pesticides that block the normal growth and reproduction of the mosquito,” Zhu said.
These members of Virginia Tech’s Vector-borne Disease Research Group are among researchers looking into how parasites spread specific diseases: