Doctors have no specific drugs to treat dengue fever, a viral illness spread by mosquitoes that sickens 50 million to 100 million people worldwide each year. Instead, the only treatments they can recommend for this painful and sometimes fatal illness (20,000 deaths globally each year) are fluids, rest and non-aspirin pain and fever reducers.
Now, researchers have identified cellular components in mosquitoes and in humans that dengue virus uses to multiply inside these hosts after infecting them. Their findings could lead to the development of anti-dengue drugs that would inhibit one or more of these host factors, thus curtailing infection and the development of disease.
The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, funded the research, which was led by Mariano Garcia-Blanco, M.D., Ph.D., of Duke University Medical Center. The research appears in the current issue of the journal Nature.
"In this important study, Dr. Garcia-Blanco and his collaborators have greatly expanded the list of candidate targets for dengue drug development," says NIAID Director Anthony S. Fauci, M.D. "Their discovery should spur a better understanding of how dengue virus causes illness and open new avenues for developing specific treatments for a disease that exacts a huge global burden."
All viruses co-opt parts of the cells they invade, but dengue virus is believed to require many such host factors because it has very little of its own genetic material, says Dr. Garcia-Blanco. Yet only a handful of mosquito or human dengue virus host factors (DVHF) have been identified to date, he adds, because researchers lack the tools for determining the functions of mosquito genes.
To overcome this barrier, the researchers turned to a familiar lab animal, the fruit fly. Mosquitoes and fruit flies (Drosophila melanogaster) are closely related, and researchers have multiple tools for determining Drosophila gene functions, notes Dr. Garcia-Blanco.
The Duke researchers screened test-tube-grown Drosophila cells to find any fly gene components used by dengue virus. They employed a technique called RNA interference (RNAi) to selectively turn off, or silence, Drosophila gene segments and identify those that dengue virus requires for efficient growth. The screen turned up 116 DVHFs, of which 111 had not previously been identified as host factors.