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J Gen Virol. 2019 Sep 17. doi: 10.1099/jgv.0.001319. [Epub ahead of print]

Increased serum sialic acid is associated with morbidity and mortality in a murine model of dengue disease.

Author information

1
Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720, USA.
2
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.

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.

KEYWORDS:

NS1; biomarker; dengue virus; sialic acid; vascular leakage

PMID:
31526452
DOI:
10.1099/jgv.0.001319

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