Understanding antibody-dependent enhancement in dengue: are afucosylated IgG1s a concern?

Dengue is a mosquito-borne infection caused by dengue virus (DENV) of the Flaviviridae family. There are four distinct serotypes, DENV-1,-2,-3,-4, which cause outbreaks globally. Infection is often self-resolving, and lifelong immunity against the infecting serotype can be achieved after exposure. H...

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Main Authors: Teo, Andrew, Tan, Hao Dong, Loy, Thomas, Chia, Po Ying, Chua, Caroline Lin Lin
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2023
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Online Access:https://hdl.handle.net/10356/169169
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1691692023-07-09T15:38:24Z Understanding antibody-dependent enhancement in dengue: are afucosylated IgG1s a concern? Teo, Andrew Tan, Hao Dong Loy, Thomas Chia, Po Ying Chua, Caroline Lin Lin Lee Kong Chian School of Medicine (LKCMedicine) National Centre for Infectious Diseases, Singapore Tan Tock Seng Hospital Science::Medicine Fucosylation FUT8 Dengue is a mosquito-borne infection caused by dengue virus (DENV) of the Flaviviridae family. There are four distinct serotypes, DENV-1,-2,-3,-4, which cause outbreaks globally. Infection is often self-resolving, and lifelong immunity against the infecting serotype can be achieved after exposure. However, in some individuals, homologous infection may still result in symptomatic dengue [1]. There is usually limited protection against heterotypic infections by three other DENV serotypes, as cross-protection is short-lived [2]. After this window of “protection”, subsequent infection with a different serotype may increase the risk of developing severe dengue [3,4]. Antibody-dependent enhancement (ADE) in dengue, a process mainly mediated by immunoglobulin G (IgG), is believed to be one of the major underlying mechanisms leading to increased severity in secondary DENV infection. ADE was shown to enhance viral entry into immune cells via their Fcγ receptors (FcγR), which promotes viral replication, leading to increased viremia and pro-inflammatory responses. These contribute to disease pathologies including vascular hyperpermeability, a common cause of severe dengue [5]. Although this pathological link was first reported about six decades ago, the inherent molecular mechanisms are still not fully understood. Here, we discuss the current model of ADE in dengue and provide new perspective on the possible roles of afucosylated IgG1s in ADE-mediated severe dengue. Nanyang Technological University Published version CLLC receives support from Ministry of Education (MOE) Fundamental Research Grant Scheme of Malaysia: ID FRGS/1/2020/SKK0/ TAYLOR/02/1. AT is supported by LKC Medicine Dean’s Postdoctoral Fellowship from Lee Kong Chian School of Medicine, Nanyang Technological University. 2023-07-04T07:14:01Z 2023-07-04T07:14:01Z 2023 Journal Article Teo, A., Tan, H. D., Loy, T., Chia, P. Y. & Chua, C. L. L. (2023). Understanding antibody-dependent enhancement in dengue: are afucosylated IgG1s a concern?. PLoS Pathogens, 19(3), 1011223-. https://dx.doi.org/10.1371/JOURNAL.PPAT.1011223 1553-7366 https://hdl.handle.net/10356/169169 10.1371/JOURNAL.PPAT.1011223 19 2-s2.0-85151573522 3 19 1011223 en PLoS Pathogens © 2023 Teo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Fucosylation
FUT8
spellingShingle Science::Medicine
Fucosylation
FUT8
Teo, Andrew
Tan, Hao Dong
Loy, Thomas
Chia, Po Ying
Chua, Caroline Lin Lin
Understanding antibody-dependent enhancement in dengue: are afucosylated IgG1s a concern?
description Dengue is a mosquito-borne infection caused by dengue virus (DENV) of the Flaviviridae family. There are four distinct serotypes, DENV-1,-2,-3,-4, which cause outbreaks globally. Infection is often self-resolving, and lifelong immunity against the infecting serotype can be achieved after exposure. However, in some individuals, homologous infection may still result in symptomatic dengue [1]. There is usually limited protection against heterotypic infections by three other DENV serotypes, as cross-protection is short-lived [2]. After this window of “protection”, subsequent infection with a different serotype may increase the risk of developing severe dengue [3,4]. Antibody-dependent enhancement (ADE) in dengue, a process mainly mediated by immunoglobulin G (IgG), is believed to be one of the major underlying mechanisms leading to increased severity in secondary DENV infection. ADE was shown to enhance viral entry into immune cells via their Fcγ receptors (FcγR), which promotes viral replication, leading to increased viremia and pro-inflammatory responses. These contribute to disease pathologies including vascular hyperpermeability, a common cause of severe dengue [5]. Although this pathological link was first reported about six decades ago, the inherent molecular mechanisms are still not fully understood. Here, we discuss the current model of ADE in dengue and provide new perspective on the possible roles of afucosylated IgG1s in ADE-mediated severe dengue.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Teo, Andrew
Tan, Hao Dong
Loy, Thomas
Chia, Po Ying
Chua, Caroline Lin Lin
format Article
author Teo, Andrew
Tan, Hao Dong
Loy, Thomas
Chia, Po Ying
Chua, Caroline Lin Lin
author_sort Teo, Andrew
title Understanding antibody-dependent enhancement in dengue: are afucosylated IgG1s a concern?
title_short Understanding antibody-dependent enhancement in dengue: are afucosylated IgG1s a concern?
title_full Understanding antibody-dependent enhancement in dengue: are afucosylated IgG1s a concern?
title_fullStr Understanding antibody-dependent enhancement in dengue: are afucosylated IgG1s a concern?
title_full_unstemmed Understanding antibody-dependent enhancement in dengue: are afucosylated IgG1s a concern?
title_sort understanding antibody-dependent enhancement in dengue: are afucosylated igg1s a concern?
publishDate 2023
url https://hdl.handle.net/10356/169169
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