Transcriptome Analysis of Monocytes Treated with Dengue NS1 Revealed a Shift in Transcripts Involving in Self-Propagated Proinflammation and Antiviral Responses.

Abstract

Non-structural protein 1 (NS1) of dengue virus (DENV) can influence dengue severity. In this study, we used RNA sequencing analysis to assess blood monocyte response to different concentrations of NS1. Here we showed that NS1 at the level found in severe dengue may be involved in severe dengue development through two potential mechanisms which were induction of excessive inflammation and suppression of antiviral responses. At high levels, NS1 significantly up-regulated S100A8 and S100A9, ACOD1, and TREM-1, that might help amplifying the inflammatory loops. In terms of antiviral suppression, we found that high NS1 concentration significantly suppressed interferon signalling and MHCII transcripts. This potentially delayed the clearance of both DENV and NS1 protein. Our study highlighted the possible role of NS1-activated monocytes in dengue severity.