Immunotranscriptomic profiling the acute and clearance phases of a human challenge dengue virus serotype 2 infection model

John P. Hanley, Huy A. Tu, Julie A. Dragon, Dorothy M. Dickson, Roxana del Rio-Guerra, Scott W. Tighe, Korin M. Eckstrom, Nicholas Selig, Samuel V. Scarpino, Stephen S. Whitehead, Anna P. Durbin, Kristen K. Pierce, Beth D. Kirkpatrick, Donna M. Rizzo, Seth Frietze and Sean A. Diehl ()
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John P. Hanley: University of Vermont
Huy A. Tu: University of Vermont
Julie A. Dragon: University of Vermont
Dorothy M. Dickson: University of Vermont
Roxana del Rio-Guerra: University of Vermont
Scott W. Tighe: University of Vermont
Korin M. Eckstrom: University of Vermont
Nicholas Selig: University of Vermont
Samuel V. Scarpino: Northeastern University
Stephen S. Whitehead: National Institute of Allergy and Infectious Diseases
Anna P. Durbin: Johns Hopkins University
Kristen K. Pierce: University of Vermont
Beth D. Kirkpatrick: University of Vermont
Donna M. Rizzo: University of Vermont
Seth Frietze: University of Vermont
Sean A. Diehl: University of Vermont

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract About 20–25% of dengue virus (DENV) infections become symptomatic ranging from self-limiting fever to shock. Immune gene expression changes during progression to severe dengue have been documented in hospitalized patients; however, baseline or kinetic information is difficult to standardize in natural infection. Here we profile the host immunotranscriptome response in humans before, during, and after infection with a partially attenuated rDEN2Δ30 challenge virus (ClinicalTrials.gov NCT02021968). Inflammatory genes including type I interferon and viral restriction pathways are induced during DENV2 viremia and return to baseline after viral clearance, while others including myeloid, migratory, humoral, and growth factor immune regulation factors pathways are found at non-baseline levels post-viremia. Furthermore, pre-infection baseline gene expression is useful to predict rDEN2Δ30-induced immune responses and the development of rash. Our results suggest a distinct immunological profile for mild rDEN2Δ30 infection and offer new potential biomarkers for characterizing primary DENV infection.

Date: 2021
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DOI: 10.1038/s41467-021-22930-6

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