Research ArticleDENGUE VIRUS

A T164S mutation in the dengue virus NS1 protein is associated with greater disease severity in mice

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Science Translational Medicine  26 Jun 2019:
Vol. 11, Issue 498, eaat7726
DOI: 10.1126/scitranslmed.aat7726

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Molecular insights into dengue virus NS1

Several hundred thousand cases of severe dengue disease occur annually worldwide. Using phylogenetic analysis of publicly available dengue virus sequences, Chan et al. now show that the T164S mutation in the dengue virus NS1 protein correlated with severe dengue epidemics in the Americas. The investigators reverse engineered this mutation into the NS1 protein of a dengue virus serotype 2 mildly infectious strain. The resulting T164S mutant dengue virus produced more secreted NS1 than wild-type virus in infected mammalian cell lines, mosquitoes, and mice. Gene expression analysis and direct measurement of factors promoting disease severity in mice revealed an association between the T164S mutation in NS1 and its lipoprotein structure.

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