In a new Science study, Duke-NUS Graduate Medical School Singapore (Duke-NUS) scientists have identified how small changes in dengue's viral genome can affect the virus' ability to manipulate human immune defences and spread more efficiently. This research is the first of its kind that examined the dengue virus starting from broad population level observations and then linked it to specific molecular interactions, to explain an outbreak. This work provides a framework for identifying genomic differences within the virus that are important for epidemic spread.
Dengue virus is endemic in over 100 countries and its global spread has increased its genetic diversity. This is problematic as genetic diversity increases the chances that new strains of dengue virus could emerge that have a greater inherent capacity to cause outbreaks.
To understand this phenomenon better, Duke-NUS Associate Professor Eng Eong Ooi led a team that identified how a new strain of dengue serotype 2 virus (DENV-2)* emerged and completely displaced an older strain of DENV-2 during the 1994 dengue epidemic in Puerto Rico. The team found three mutations in the tail of the dengue genome that enabled the virus to make short fragments of genomic material, which consisted exclusively of its tail. The tail is how the virus got its sting or potency, as it was the tail that bound to a protein and supressed the human antiviral response. The suppressed human antiviral response allowed the new strain of DENV-2 to then spread more efficiently within an infected individual and increased its chances of infecting fresh mosquitoes for virus transmission.
The study provides unique insights into what determines dengue virus resilience in a real life setting. It also suggests that combining population studies with molecular investigations result in genetic information that explains virus evolution better, and that could be further developed into a predictor of epidemics.
"Firstly, our findings show that not all dengue viruses have the same ability to cause epidemics," said Dr. Ooi, who is Deputy Director the Emerging Infectious Diseases (EID) Programme at Duke-NUS. "Secondly, they imply that identifying the molecular signatures that allow the viruses to spread more efficiently could help focus public health resources on more important strains of viruses."
Singapore, and other countries where dengue is endemic, could use the framework in this study to identify the genomic differences in dengue that impacts epidemic emergence. Cataloguing the differences could then facilitate how genomic information can be used to guide dengue surveillance and response better.
Study authors include first author Gayathiri Manokaran from Duke-NUS and the National University of Singapore, co-author Professor Mariano Garcia-Blanco from Duke-NUS and other national and international collaborators.
*Dengue virus has four serotypes (DENV1-4) circulating in nature.