Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, United States.
Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, United States.
Elife. 2018 Mar 20;7:e31919. doi: 10.7554/eLife.31919.
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.
人类登革热病毒起源于灵长类动物的宿主，但奇怪的是，登革热在灵长类动物模型中不会达到高滴度。这为研究溢出宿主和储存宿主的遗传学提供了一个独特的机会。登革热病毒 2 型（DENV2）编码的蛋白酶可切割人类 STING，减少 I 型干扰素的产生，并提高人类的病毒滴度。我们发现，无论是人类还是丛林（储存）登革热病毒，都普遍能切割人类的 STING，但不能切割被认为是储存物种的灵长类动物的 STING。因此，登革热病毒切割 STING 的特殊能力是专门针对人类和少数与其关系密切的猿类物种的。将残基 78/79 转换为人类编码的“RG”，可使所有灵长类（和小鼠）的 STING 对病毒切割敏感。登革热病毒可能已经进化为了在密集而庞大的人群中提高病毒滴度，同时在作为其在自然界中维持宿主的稀有动物中保持降低的滴度和致病性。
