Scientists discover why some dengue fever viruses are more virulent than others, paving the way for vaccines, treatments
Release | Monday Aug 10, 2009
SFBR news release
For the first time, scientists have found in mice clues to why some strains of the dengue fever virus are more severe than others, an important step toward developing a vaccine against the most deadly types, say researchers at the Southwest Foundation for Biomedical Research (SFBR).
“The results point to the Southeast Asian virus, as the most virulent and the one that should be prioritized for elimination or control,” said SFBR virologist Rebeca Rico-Hesse, Ph.D., senior author on a new study appearing in the Journal of Virology.
Dengue viruses, which cause dengue fever and its more severe form, dengue hemorrhagic fever, in humans, have been spreading to more areas of the world along with their mosquito carriers. Now over 100 countries are affected, including Texas and Hawaii in the United States. Because only humans show clinical signs and symptoms of disease, it has been difficult to directly test the mechanisms of pathogenesis of these viruses.
Some 2.5 billion people – two fifths of the world's population – are at risk from dengue, according to the World Health Organization, which estimates there may be 50 million dengue infections worldwide every year.
In the new study, Rico-Hesse and her colleague Javier Mota, Ph.D., found that different genetic variants of dengue virus cause different clinical signs in mice reconstituted with human immune system cells. Demonstrating differences in growth and transmission rates is important so that scientists can to determine what makes a dengue virus more dangerous or important for public health control, Rico-Hesse said.
In the new study, newborn mice were inoculated with human umbilical cord blood-derived cells and infected with one of eight strains in amounts equivalent to a mosquito bite. After six weeks, they observed a significant decrease in blood platelets in most of the mice and an increase in fever and rash in comparison with control animals. They found that the infection of humanized mice with the four distinct genetic variants of dengue virus can induce the development of human-like disease. The Southeast Asian genetic variants of virus produced higher levels of the virus and rash in infected mice compared with American, Indian and West African types of virus.
Further experiments are planned using other human factors on the mice, to get them to make specific antibodies to the viruses, to see if the mice develop dengue hemorrhagic fever. Studies have begun to examine how lab-infected mosquitoes transmit the virus by bite to the mice, rather than by injection which will mimic the natural cycle of disease in the laboratory and measure how many bites it takes to get disease. Vaccines or antivirals could then be developed.
Rico-Hesse can be reached through Joe Carey, SFBR’s Vice President for Public Affairs, at 210-258-9437.
SFBR is one of the world's leading independent biomedical research institutions dedicated to advancing health worldwide through innovative biomedical research. Located on a 200-acre campus on the northwest side of San Antonio, Texas, SFBR partners with hundreds of researchers and institutions around the world, targeting advances in the fight against cardiovascular disease, diabetes, obesity, cancer, psychiatric disorders, problems of pregnancy, AIDS, hepatitis, malaria, parasitic infections and a host of other infectious diseases. For more information on SFBR, go to www.sfbr.org.
