@article{mbs:/content/journal/jgv/10.1099/jgv.0.001319, author = "Espinosa, Diego A. and Beatty, P. Robert and Puerta-Guardo, Henry and Islam, M. Nurul and Belisle, John T. and Perera, Rushika and Harris, Eva", title = "Increased serum sialic acid is associated with morbidity and mortality in a murine model of dengue disease", journal= "Journal of General Virology", year = "2019", volume = "100", number = "11", pages = "1515-1522", doi = "https://doi.org/10.1099/jgv.0.001319", url = "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.001319", publisher = "Microbiology Society", issn = "1465-2099", type = "Journal Article", keywords = "dengue virus", keywords = "NS1", keywords = "sialic acid", keywords = "biomarker", keywords = "vascular leakage", abstract = "Dengue virus (DENV) causes the most prevalent arboviral infection of humans, resulting in a spectrum of outcomes, ranging from asymptomatic infection to dengue fever to severe dengue characterized by vascular leakage and shock. Previously, we determined that DENV nonstructural protein 1 (NS1) induces endothelial hyperpermeability, disrupts the endothelial glycocalyx layer (EGL) in vitro and triggers shedding of structural components, including sialic acid (Sia) and heparan sulfate. Here, using a murine model of dengue disease disease, we found high levels of Sia and NS1 circulating in mice with DENV-induced morbidity and lethal DENV infection. Further, we developed a liquid chromatography/mass spectrometry-based method for quantifying free Sia in serum and determined that the levels of free N-glycolylneuraminic acid were significantly higher in DENV-infected mice than in uninfected controls. These data provide additional evidence that DENV infection disrupts EGL components in vivo and warrant further research assessing Sia as a biomarker of severe dengue disease.", }