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

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 rDEN2Delta30 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 rDEN2Delta30-induced immune responses and the development of rash. Our results suggest a distinct immunological profile for mild rDEN2Delta30 infection and offer new potential biomarkers for characterizing primary DENV infection.

Authors: Hanley JP, Tu HA, Dragon JA, Dickson DM, Rio-Guerra RD, Tighe SW, Eckstrom KM, Selig N, Scarpino SV, Whitehead SS, Durbin AP, Pierce KK, Kirkpatrick BD, Rizzo DM, Frietze S, Diehl SA,
Journal: Nat Commun; 2021 May 24 ; 12 (1) 3054. doi:10.1038/s41467-021-22930-6
Year: 2021
PubMed: PMID: 34031380 (Go to PubMed)