Dengue viruses cleave STING in humans but not in nonhuman primates, their presumed natural reservoir

Dengue viruses are found in over 100 countries and cause the tropical disease known as dengue fever. Dengue viruses affect around 100 million people per year and can – in severe cases – lead to death. Unlike many other deadly diseases, there is currently no vaccine that completely prevents dengue fever. It is thought that dengue viruses that circulate in human populations were derived from monkey versions of that same virus. However, research suggests that both human and primate variations of dengue viruses appear to multiply much better in humans than in other species. Scientists believe that this is because some animals, including primates, have defense mechanisms that are ineffective in humans. To explore this idea, Stabell et al. looked at a protein called STING in humans and in three different primates: the chimpanzee, the rhesus macaque, and the common marmoset. STING plays an important role in the immune system and helps to fight infections caused by viruses and other microbes. During replication – the process by which a virus spreads through an organism’s cells – the dengue virus cuts and inactivates the human STING protein, and so helps the virus spread. Stabell et al. discovered that in most primates, dengue viruses cannot inactivate STING. This was found to be reliant on a small region in the STING protein that differed between humans and primates. This small difference may, in part, explain why dengue viruses replicate better in humans than other primates. Stabell et al. then searched for other animals whose STING protein would be susceptible to dengue virus inactivation. Using a database with genetic information of over 5,000 mammals, Stabell et al. identified STING proteins of three types of apes and three types of rodents that could also be deactivated by dengue viruses. To develop a vaccine or antiviral drug scientists generally need to study the disease in living animals. Since dengue viruses replicate more successfully in humans than they do in other animal models, it makes it more challenging to find an effective treatment. The results from Stabell et al. may help to identify animals that could be strong candidates for future research into dengue viruses, potentially paving the way for further therapeutic development.