Treating Dengue Fever
School of Medicine
AURORA, Colo. – 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.
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.
than 40 percent of people around the world are at risk of being bitten by
mosquitoes infected with the virus 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
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 enzyme
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.
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
understanding of how an RNA found in many different flaviviruses thwarts a
powerful enzyme may help scientists develop treatments or vaccines.
is the corresponding author of the eLife aticle. The other authors are Erich G.
Chapman, PhD, Stephanie L. Moon and Jeffrey Wilusz, PhD, professor of
microbiology, immunology and pathology at Colorado State University. Kieft is
also the corresponding author of the Science aticle. The other authors on the Science
article are Chapman, David A. Costantino, MS, Jay C. Nix, PhD, Moon, and
Wilusz. Funding was provided by the Howard Hughes Medical Institute and the
National Institutes of Health