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.

中文翻译：

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登革热病毒在人类中切割 STING，但不在非人类灵长类动物中切割，这是它们假定的天然宿主

人类登革热病毒从灵长类动物宿主中出现，但矛盾的是，登革热病毒在灵长类动物模型中并未达到高滴度。这提供了一个独特的机会来检查溢出与水库宿主的遗传学。登革热病毒 2 (DENV2) - 编码的蛋白酶切割人类 STING，减少 I 型干扰素的产生并提高人类的病毒滴度。我们发现人类和森林（水库）登革热病毒普遍切割人类 STING，但不能切割与水库物种有关的灵长类动物的 STING。因此，登革热切割 STING 的特殊能力是人类和一些密切相关的猿类所特有的。将残基 78/79 转换为人类编码的“RG”，使所有灵长类动物（和小鼠）STING 对病毒切割敏感。登革热病毒可能已经进化为在密集而庞大的人群中增加病毒滴度，