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DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion

The major structural envelope (E) protein of Japanese encephalitis virus (JEV) facilitates cellular binding/entry and is the primary target of neutralizing antibodies. JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation si...

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Autores principales: Liang, Jian-Jong, Chou, Min-Wei, Lin, Yi-Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048278/
https://www.ncbi.nlm.nih.gov/pubmed/30042931
http://dx.doi.org/10.3389/fcimb.2018.00239
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author Liang, Jian-Jong
Chou, Min-Wei
Lin, Yi-Ling
author_facet Liang, Jian-Jong
Chou, Min-Wei
Lin, Yi-Ling
author_sort Liang, Jian-Jong
collection PubMed
description The major structural envelope (E) protein of Japanese encephalitis virus (JEV) facilitates cellular binding/entry and is the primary target of neutralizing antibodies. JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site). We generated three recombinant JEVs with different glycosylation patterns on the E protein. As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation. The G1G2 mutant (E-D67N), with E-glycosylation on both G1 and G2 sites, showed potent in vitro viral replication and in vivo neurovirulence, but reduced neuroinvasiveness. Furthermore, the JEV mutants with G1 glycosylation showed enhanced DC-SIGN binding, which may then lead to reduced brain invasion and explain the reason why WT JEV is devoid of this G1 site of glycosylation. Overall, the patterns of N-linked glycosylation on JEV E proteins may affect viral interaction with cellular lectins and contribute to viral replication and pathogenesis.
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spelling pubmed-60482782018-07-24 DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion Liang, Jian-Jong Chou, Min-Wei Lin, Yi-Ling Front Cell Infect Microbiol Cellular and Infection Microbiology The major structural envelope (E) protein of Japanese encephalitis virus (JEV) facilitates cellular binding/entry and is the primary target of neutralizing antibodies. JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site). We generated three recombinant JEVs with different glycosylation patterns on the E protein. As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation. The G1G2 mutant (E-D67N), with E-glycosylation on both G1 and G2 sites, showed potent in vitro viral replication and in vivo neurovirulence, but reduced neuroinvasiveness. Furthermore, the JEV mutants with G1 glycosylation showed enhanced DC-SIGN binding, which may then lead to reduced brain invasion and explain the reason why WT JEV is devoid of this G1 site of glycosylation. Overall, the patterns of N-linked glycosylation on JEV E proteins may affect viral interaction with cellular lectins and contribute to viral replication and pathogenesis. Frontiers Media S.A. 2018-07-10 /pmc/articles/PMC6048278/ /pubmed/30042931 http://dx.doi.org/10.3389/fcimb.2018.00239 Text en Copyright © 2018 Liang, Chou and Lin. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Liang, Jian-Jong
Chou, Min-Wei
Lin, Yi-Ling
DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion
title DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion
title_full DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion
title_fullStr DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion
title_full_unstemmed DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion
title_short DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion
title_sort dc-sign binding contributed by an extra n-linked glycosylation on japanese encephalitis virus envelope protein reduces the ability of viral brain invasion
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048278/
https://www.ncbi.nlm.nih.gov/pubmed/30042931
http://dx.doi.org/10.3389/fcimb.2018.00239
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