Profiling an Enhanced IL-6 Expression Distinguishes Host Susceptibility to Primary and Secondary Infections of the Dengue Virus in an Ex Vivo Whole-Blood Coculture Model

Sep 28, 2026

Uploaded by Finn

Dengue virus infection can progress to severe disease through antibody-dependent enhancement. This study compares host cytokine/chemokine responses during primary versus secondary dengue infection using an artificial ex vivo whole-blood coculture model to mimic acute febrile-phase viremia. A customized dengue multiplex assay shows secondary infection does not worsen hematological or cytopathological outcomes, but increases MIP-1α, MIP-1β, IL-6, TNF-α, and RANTES, while NS1 decreases. Pre-existing anti-E antibodies correlate with IL-6 overproduction, supporting NS1- and IL-6-based susceptibility assessment.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Introduction

Materials and Methods

Cells and Virus Culture

Wiley Journal of Tropical Medicine Volume 2026, Article ID 9350179, 12 pages [https://doi.org/10.1155/jotm/9350179](https://doi.org/10.1155/jotm/9350179) Research Article Profiling an Enhanced IL-6 Expression Distinguishes Host Susceptibility to Primary and Secondary Infections ofthe Dengue Virus in an Ex Vivo Whole-Blood Coculture Model Josephine Diony Nanda,1,2 Ming-Kai Jhan, 1 Rahmat Dani Satria,3,4 Yung-Ting Wang, 1 Tzong-Shiann Ho ,5,6,7 Herdiantri Sufriyana,8 Emily Chia-Yu Su ,8,9,10 and Chiou-Feng Lin 1,11,12 1 Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan 2 Department of Parasitology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia 3 Department of Clinical Pathology and Laboratory Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia 4 Clinical Laboratory Installation, Dr. Sardjito Central General Hospital, Yogyakarta 55281, Indonesia 5 Department of Paediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan 6 Department of Paediatrics, National Cheng Kung University Hospital Dou-Liou Branch, College of Medicine, National Cheng Kung University, Yunlin 640, Taiwan 7 Center of Infectious Disease and Signalling Research, National Cheng Kung University, Tainan, Taiwan 8 Institute of Biomedical Informatics, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan 9 Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan 10 Clinical Big Data Research Center, Taipei Medical University Hospital, Taipei, Taiwan 11 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan 12 Core Laboratory of Immune Monitoring, Ofce of Research & Development, Taipei Medical University, Taipei 110, Taiwan Correspondence should be addressed to Chiou-Feng Lin; [cfin2014@tmu.edu.tw](cfin2014@tmu.edu.tw) Received 12 February 2025; Revised 31 August 2025; Accepted 27 November 2025 Guest Editor: Biswadeep Das Copyright © 2026 Josephine Diony Nanda et al. Journal of Tropical Medicine published by John Wiley & Sons Ltd. Tis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Dengue virus (DENV) infection can potentially lead to severe dengue disease due to the risk of antibody-dependent enhancement. Tis study reports a comparative analysis of the host cytokine/chemokine response triggered by primary and secondary DENV infections using an artifcial ex vivo whole-blood coculture model to simulate viremia during the acute febrile phase of infection. Using ex vivo primary and secondary DENV infection modes, a dengue-specifc customized multiplex cytokine/chemokine assay was employed. Secondary infection did not exacerbate DENV-induced hematological and cytopathological changes, such as alterations in complete blood count, intracellular vacuolization, and thrombophagocytosis. However, cytokine/chemokine assay revealed a signifcant increase in the production of MIP-1α, MIP-1β, IL-6, TNF-α, and RANTES. Notably, a substantial decrease in NS1 levels indicated the neutralization efect in individuals with prior DENV exposure or secondary infection group, especially in some cases of secondary infection. Tis was accompanied by pre-existing anti-E antibodies, highly associated with IL-6 overproduction. Tese fndings support the potential strategy of assessing DENV susceptibility using NS1 and IL-6 using an ex vivo method. Keywords: DENV; ex vivo; IL-6; infection; NS1 2 Journal of Tropical Medicine 1. Introduction 2. Materials and Methods Te dengue virus (DENV), transmit

FAQs

How does the study model primary and secondary dengue infection?

It uses an artificial ex vivo whole-blood coculture model with ex vivo primary and secondary DENV infection modes to simulate viremia during the acute febrile phase.

What key hematological and cytopathological effects differ between primary and secondary infection?

Secondary infection does not exacerbate DENV-induced hematological and cytopathological changes, including alterations in complete blood count, intracellular vacuolization, and thrombophagocytosis.

Which biomarkers and immune mediators show significant changes?

The multiplex assay shows increased MIP-1α, MIP-1β, IL-6, TNF-α, and RANTES, alongside a substantial decrease in NS1 levels.

How do prior exposure and antibodies relate to IL-6 production?

Pre-existing anti-E antibodies are highly associated with IL-6 overproduction, and decreased NS1 suggests neutralization effects in individuals with prior DENV exposure or in the secondary infection group.

Sep 28, 2026

Uploaded by Finn