Abstract
Human dengue viruses emerged from primate reservoirs, yet paradoxically dengue does not reach high titers in primate models. This presents a unique opportunity to examine the genetics of spillover versus reservoir hosts. The dengue virus 2 (DENV2) - encoded protease cleaves human STING, reducing type I interferon production and boosting viral titers in humans. We find that both human and sylvatic (reservoir) dengue viruses universally cleave human STING, but not the STING of primates implicated as reservoir species. The special ability of dengue to cleave STING is thus specific to humans and a few closely related ape species. Conversion of residues 78/79 to the human-encoded 'RG' renders all primate (and mouse) STINGs sensitive to viral cleavage. Dengue viruses may have evolved to increase viral titers in the dense and vast human population, while maintaining decreased titers and pathogenicity in the more rare animals that serve as their sustaining reservoir in nature.
Highlights
Dengue viruses cause clinical disease in approximately 100 million individuals each year and are found in over 100 countries (Bhatt et al, 2013)
We show that an ‘RG’ motif at positions 78/79 of STING is critical for susceptibility to cleavage, and conversion of these residues to ‘RG’ renders all nonhuman primate STING proteins tested, as well as mouse STING, sensitive to dengue virus proteases
The human STING being cleaved, but this is consistent with previous publications and is presumably exacerbated by the overexpression of STING achieved in transfection experiments (Aguirre et al, 2012; Yu et al, 2012)
Summary
Dengue viruses cause clinical disease in approximately 100 million individuals each year and are found in over 100 countries (Bhatt et al, 2013). Dengue viruses are positive sense RNA viruses in the family Flaviviridae, and are related to yellow fever virus, Zika virus, and West Nile virus (Best, 2016). These viruses are primarily transmitted between humans in highly populated areas by Aedes aegypti and Aedes albopictus mosquitoes, in what are referred to as human (or ‘urban’) transmission cycles (Diamond and Pierson, 2015; Hanley et al, 2013; Vasilakis et al, 2011).
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call