Maternal Anti-Dengue IgG Fucosylation Predicts Susceptibility to Dengue Disease in Infants
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Authors
Thulin, Natalie K.Brewer, R. Camille
Sherwood, Robert
Bournazos, Stylianos
Edwards, Karlie G.
Ramadoss, Nitya S.
Taubenberger, Jeffery K.
Memoli, Matthew
Gentles, Andrew J.
Jagannathan, Prasanna
Zhang, Sheng
Libraty, Daniel H.
Wang, Taia T.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2020-05-12Keywords
CD16FcγRIIIa
IgG fucosylation
antibody glycosylation
infant dengue
severe dengue
Amino Acids, Peptides, and Proteins
Immunology of Infectious Disease
Immunopathology
Infectious Disease
Maternal and Child Health
Virus Diseases
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Show full item recordAbstract
Infant mortality from dengue disease is a devastating global health burden that could be minimized with the ability to identify susceptibility for severe disease prior to infection. Although most primary infant dengue infections are asymptomatic, maternally derived anti-dengue immunoglobulin G (IgGs) present during infection can trigger progression to severe disease through antibody-dependent enhancement mechanisms. Importantly, specific characteristics of maternal IgGs that herald progression to severe infant dengue are unknown. Here, we define > /=10% afucosylation of maternal anti-dengue IgGs as a risk factor for susceptibility of infants to symptomatic dengue infections. Mechanistic experiments show that afucosylation of anti-dengue IgGs promotes FcgammaRIIIa signaling during infection, in turn enhancing dengue virus replication in FcgammaRIIIa(+) monocytes. These studies identify a post-translational modification of anti-dengue IgGs that correlates with risk for symptomatic infant dengue infections and define a mechanism by which afucosylated antibodies and FcgammaRIIIa enhance dengue infections.Source
Thulin NK, Brewer RC, Sherwood R, Bournazos S, Edwards KG, Ramadoss NS, Taubenberger JK, Memoli M, Gentles AJ, Jagannathan P, Zhang S, Libraty DH, Wang TT. Maternal Anti-Dengue IgG Fucosylation Predicts Susceptibility to Dengue Disease in Infants. Cell Rep. 2020 May 12;31(6):107642. doi: 10.1016/j.celrep.2020.107642. PMID: 32402275. Link to article on publisher's site
DOI
10.1016/j.celrep.2020.107642Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41458PubMed ID
32402275Related Resources
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Copyright 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2020.107642
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Except where otherwise noted, this item's license is described as Copyright 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/