Stabell et al. have revealed why human dengue viruses do not replicate to high titres in primate models. They found that the stimulator of interferon genes (STING) protein, which induces the production of type I interferon in infected cells to reduce viral titres, is cleaved by the dengue virus protease NS2B3 in humans but not in key primate models. STING cleavage occurred at an RG motif at amino acids 78 and 79, decreasing markers of an innate immune response and increasing viral replication in human cells. The analyses of STING sequences from all placental animals in Genbank, as well as from 16 non-human primate cell lines, revealed that only STING from three small apes and three small rodents encodes this RG motif. As introducing this RG motif into STING from rhesus macaque, marmoset and mouse rendered it susceptible to cleavage by dengue virus NS2B3, engineering model organisms so that their STING contains this motif could enhance the study of dengue viruses in animals.
Stabell, A. C. et al. Dengue viruses cleave STING in humans but not in nonhuman primates, their presumed natural reservoir. eLife 2018, e31919 (2018)
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Wrighton, K. The STING behind dengue virus infection. Nat Rev Microbiol 16, 330 (2018). https://doi.org/10.1038/s41579-018-0010-7