Researchers discover target for treating dengue fever

Two recent papers by a University of Colorado School of Medicine researcher and colleagues may help scientists develop treatments or vaccines for Dengue fever, West Nile virus, Yellow fever, Japanese encephalitis and other disease-causing flaviviruses.

Jeffrey S. Kieft, PhD, associate professor of biochemistry and molecular genetics at the School of Medicine and an early career scientist with the Howard Hughes Medical Institute, and colleagues recently published articles in the scholarly journals eLife and Science that explain how flaviviruses produce a unique RNA molecule that leads to disease.

More than 40 percent of people around the world are at risk of being bitten by mosquitoes infected with the that causes Dengue fever and more than 100 million people are infected, according to eLife. Many develop headaches, pain and fever, but some develop a life-threatening condition where tiny blood vessels in the body begin to leak. Other flaviviruses, such as West Nile virus, are rapidly spreading around the globe. Flaviviruses are considered dangerous emerging pathogens.

The eLife paper shows that the virus causing Dengue fever and other closely related viruses like West Nile and Japanese encephalitis use instructions encoded on a single strand of RNA to take over an infected cell and reproduce. The viruses also exploit an that cells use to destroy RNA to instead produce short stretches of RNA that, among other things, may help the virus avoid the immune system of its host. Ironically, these viruses use a structured RNA molecule to resist an enzyme that normally "chews up" RNA.

The Science paper reveals the discovery that the resistant RNA folds up into an unprecedented "knot-like" structure. The enzyme, normally adept at breaking up RNA structure, encounters this particular structured RNA and cannot "untangle" it; thus the enzyme is thwarted. This is the first time this sort of RNA structure has been observed and it has characteristics that may be amenable to targeting by new drugs. To discover this structure, the researchers used a technique called x-ray crystallography, which allowed them to determine the structures of individual molecules.

This understanding of how an RNA found in many different flaviviruses thwarts a powerful enzyme may help scientists develop treatments or vaccines.

More information: "The Structural Basis of Pathogenic Subgenomic Flavivirus RNA (sfRNA) Production," by E.G. Chapman et al. Science, 2014.

add to favorites email to friend print save as pdf

Related Stories

Trick that aids viral infection is identified

Jan 30, 2014

Scientists have identified a way some viruses protect themselves from the immune system's efforts to stop infections, a finding that may make new approaches to treating viral infections possible.

Making the most of what you have

Oct 08, 2013

Understanding how viral proteins are produced can provide important clues on how we might interfere with the process. The group of Till Rümenapf at the University of Veterinary Medicine Vienna has discovered ...

Scientists identify antivirus system

Nov 17, 2010

(PhysOrg.com) -- Viruses have led scientists at Washington University School of Medicine in St. Louis to the discovery of a security system in host cells.

New West Nile and Japanese encephalitis vaccines produced

May 30, 2008

University of Texas Medical Branch at Galveston researchers have developed new vaccines to protect against West Nile and Japanese encephalitis viruses. The investigators created the vaccines using an innovative technique ...

Recommended for you

New analysis questions use of acute hemodialysis treatment

2 hours ago

A common approach to treating kidney failure by removing waste products from the blood did not improve survival chances for people who suddenly developed the condition, in an analysis led by experts at the University of Pittsburgh ...

WHO: West Africa Ebola death toll rises to 1,350

2 hours ago

Security forces acting on the president's orders used scrap wood and barbed wire to seal off 50,000 people inside their crowded slum Wednesday in an attempt to contain the Ebola outbreak, which has killed ...

User comments