Saisingha Khwankhao, Jearanaiwitayakul Tuksin, Watterson Daniel, Modhiran Naphak, Ponpuak Marisa, Ubol Sukathida
Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Department of Clinical Pathology, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand.
J Infect Dis. 2025 Jul 11;231(6):e1170-e1182. doi: 10.1093/infdis/jiaf166.
Nonstructural protein 1 (NS1) of dengue virus (DENV) can influence dengue severity. In this study, we used RNA sequencing analysis to assess the blood monocyte response to different concentrations of NS1. We showed that NS1 at the level found in severe dengue may be involved in severe dengue development through 2 potential mechanisms: induction of excessive inflammation and suppression of antiviral responses. At high levels, NS1 significantly up-regulated S100A8 and S100A9, ACOD1, and TREM1, which might help amplify the inflammatory loops. In terms of antiviral suppression, we found that high NS1 concentration significantly suppressed interferon signaling and major histocompatibililty complex class II 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.
登革病毒（DENV）的非结构蛋白1（NS1）可影响登革热的严重程度。在本研究中，我们使用RNA测序分析来评估血液单核细胞对不同浓度NS1的反应。我们发现，严重登革热中所发现水平的NS1可能通过两种潜在机制参与严重登革热的发展：诱导过度炎症反应和抑制抗病毒反应。在高水平时，NS1显著上调S100A8和S100A9、ACOD1以及TREM1，这可能有助于放大炎症循环。在抗病毒抑制方面，我们发现高浓度NS1显著抑制干扰素信号传导和主要组织相容性复合体II类转录本。这可能会延迟登革病毒和NS1蛋白的清除。我们的研究强调了NS1激活的单核细胞在登革热严重程度中可能发挥的作用。
