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Elife
2018 ; 7
(?): ? Nephropedia Template TP
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Dengue viruses cleave STING in humans but not in nonhuman primates, their
presumed natural reservoir
#MMPMID29557779
Stabell AC
; Meyerson NR
; Gullberg RC
; Gilchrist AR
; Webb KJ
; Old WM
; Perera R
; Sawyer SL
Elife
2018[Mar]; 7
(?): ? PMID29557779
show ga
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.
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