Welcome news on Dengue fever

Apr 26 2009

The news that scientists in the United States have identified host factors which are critical to Dengue virus infection will be particularly welcome in tropical northern Queensland, which has suffered one of the worse Dengue fever outbreaks in decades.

The Dengue virus is spread among humans by the Aedes agypti mosquito and experts in Australia have warned that Dengue fever is likely to become endemic in the tropical north unless firmer action is taken.

But news that scientists at Duke University Medical Center have identified dozens of proteins the Dengue fever virus depends upon to grow and spread among mosquitoes and humans, offers some hope of preventing and treating the disease which affects millions of people around the world every year.

Dengue fever is a mosquito-borne illness that can cause debilitating sickness and death - according to the World Health Organization (WHO), almost half the people in the world are vulnerable to the Dengue virus.

There is growing concern amongst health officials because Dengue appears to be now occurring in places where it has rarely appeared before and there is the suspicion that the current epidemics may be exacerbated by global warming.

The scientists say Dengue is a 'nasty' disease, with no treatment and little which can be done to prevent it.

Dr. Mariano Garcia-Blanco, a professor of molecular genetics and microbiology at Duke University Medical Center in North Carolina and senior author of the study says if a weakness in the virus can be found, a strategy to fight it can be designed and the study has helped identify some gaps in Dengue's armour.

Dr. Garcia-Blanco, who is also professor of emerging infectious diseases at the Duke-NUS Graduate Medical School in Singapore, used RNA interference (RNAi) to unlock Dengue's secrets - a normal biological process cells use to turn gene expression on or off depending upon which gene products, or proteins, are needed at any given moment.

He says that very same system proved to be the perfect investigative tool, for they were able to knock down gene function in fruit fly cells infected with a strain of the Dengue virus known as DENV-2 , and by silencing one gene at a time (there were about 14,000 of them), the researchers were able to pinpoint which genes, or host factors, were essential to viral growth and which ones were not.

Fruit flies were used as a model because the genetic tools needed for the same work in mosquitoes have not been developed yet.

The process yielded 116 host factors that appeared to be important to successful Dengue infection in fruit flies and testing revealed that at least one - and possibly a second - was necessary for Dengue infection to occur in the insects.

Scientists also infected human cells with the DENV-2 virus and found 82 of the mosquito genes had analogous genes in humans and about half that number turned out to be Dengue-specific host factors important in human infection.

Dr. Garcia-Blanco says each one of these newly identified host factors is a potential therapeutic target that could be used to block or slow Dengue infection and as there are currently no vaccines to prevent the disease, new ways to fight the disease are important.

Dr. Garcia-Blanco says there are already a couple of Dengue vaccine candidates in development.

The scientists say the study which was funded by the National Institute of Allergy and Infectious Diseases, a part of the National Institutes of Health, reflects the value of the growing research partnership between Duke University Medical Center and the two-year old Duke-NUS Graduate Medical School in Singapore.

Queensland Health has also turned to Singapore experts in preventing Dengue becoming endemic, with international experts attending a special summit in Cairns to help Queensland Health adDr.ess the problem of eradicating the virus before the next wet season.

Dr. Scott Ritchie from the Tropical Population Health says more cases could re-emerge in May following rain over Easter - of the 963 cases in the current outbreak in North Queensland, 890 have been recorded in the Far North and for the first time, all four strains of Dengue fever were circulating simultaneously in North Queensland.

The research appears in the April 23 issue of the journal Nature.