Cargando…

Glycosylation on envelope glycoprotein of duck Tembusu virus affects virus replication in vitro and contributes to the neurovirulence and pathogenicity in vivo

Duck Tembusu virus (DTMUV), an emergent flavivirus, causes domestic waterfowls to suffer from severe egg-drop syndrome and fatal encephalitis, greatly threatens duck production globally. Like other mosquito-borne flaviviruses, the envelope (E) protein of all DTMUV strains was N-glycosylated at the a...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Dejian, Xiao, Xuyao, Zhou, Peng, Zheng, Huijun, Li, Yaqian, Jin, Hui, Jongkaewwattana, Anan, Luo, Rui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437475/
https://www.ncbi.nlm.nih.gov/pubmed/34506259
http://dx.doi.org/10.1080/21505594.2021.1974329
_version_ 1783752174048641024
author Liu, Dejian
Xiao, Xuyao
Zhou, Peng
Zheng, Huijun
Li, Yaqian
Jin, Hui
Jongkaewwattana, Anan
Luo, Rui
author_facet Liu, Dejian
Xiao, Xuyao
Zhou, Peng
Zheng, Huijun
Li, Yaqian
Jin, Hui
Jongkaewwattana, Anan
Luo, Rui
author_sort Liu, Dejian
collection PubMed
description Duck Tembusu virus (DTMUV), an emergent flavivirus, causes domestic waterfowls to suffer from severe egg-drop syndrome and fatal encephalitis, greatly threatens duck production globally. Like other mosquito-borne flaviviruses, the envelope (E) protein of all DTMUV strains was N-glycosylated at the amino acid position 154. Thus far, the biological roles of DTMUV E glycosylation have remained largely unexplored. Herein, we demonstrated the key roles of E glycosylation in the replication and pathogenicity of DTMUV in ducks by characterizing the reverse-genetics-derived DTMUV wild-type MC strain and MC bearing mutations (N154Q and N154I) that abolish the E glycosylation. Our data showed that the disruption of E glycosylation could substantially impair virus attachment, entry, and infectivity in DEFs and C6/36 cells. Notably, ducks inoculated intracerebrally with the wild-type virus exhibited severe disease onset. In contrast, those inoculated with mutant viruses were mildly affected as manifested by minimal weight loss, no mortality, lower viral loads in the various tissues, and reduced brain lesions. Attenuated phenotypes of the mutant viruses might be partly associated with lower inflammatory cytokines expression in the brains of infected ducks. Our study offers the first evidence that E glycosylation is vital for DTMUV replication, pathogenicity, and neurovirulence in vivo.
format Online
Article
Text
id pubmed-8437475
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Taylor & Francis
record_format MEDLINE/PubMed
spelling pubmed-84374752021-09-14 Glycosylation on envelope glycoprotein of duck Tembusu virus affects virus replication in vitro and contributes to the neurovirulence and pathogenicity in vivo Liu, Dejian Xiao, Xuyao Zhou, Peng Zheng, Huijun Li, Yaqian Jin, Hui Jongkaewwattana, Anan Luo, Rui Virulence Research Paper Duck Tembusu virus (DTMUV), an emergent flavivirus, causes domestic waterfowls to suffer from severe egg-drop syndrome and fatal encephalitis, greatly threatens duck production globally. Like other mosquito-borne flaviviruses, the envelope (E) protein of all DTMUV strains was N-glycosylated at the amino acid position 154. Thus far, the biological roles of DTMUV E glycosylation have remained largely unexplored. Herein, we demonstrated the key roles of E glycosylation in the replication and pathogenicity of DTMUV in ducks by characterizing the reverse-genetics-derived DTMUV wild-type MC strain and MC bearing mutations (N154Q and N154I) that abolish the E glycosylation. Our data showed that the disruption of E glycosylation could substantially impair virus attachment, entry, and infectivity in DEFs and C6/36 cells. Notably, ducks inoculated intracerebrally with the wild-type virus exhibited severe disease onset. In contrast, those inoculated with mutant viruses were mildly affected as manifested by minimal weight loss, no mortality, lower viral loads in the various tissues, and reduced brain lesions. Attenuated phenotypes of the mutant viruses might be partly associated with lower inflammatory cytokines expression in the brains of infected ducks. Our study offers the first evidence that E glycosylation is vital for DTMUV replication, pathogenicity, and neurovirulence in vivo. Taylor & Francis 2021-09-10 /pmc/articles/PMC8437475/ /pubmed/34506259 http://dx.doi.org/10.1080/21505594.2021.1974329 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Liu, Dejian
Xiao, Xuyao
Zhou, Peng
Zheng, Huijun
Li, Yaqian
Jin, Hui
Jongkaewwattana, Anan
Luo, Rui
Glycosylation on envelope glycoprotein of duck Tembusu virus affects virus replication in vitro and contributes to the neurovirulence and pathogenicity in vivo
title Glycosylation on envelope glycoprotein of duck Tembusu virus affects virus replication in vitro and contributes to the neurovirulence and pathogenicity in vivo
title_full Glycosylation on envelope glycoprotein of duck Tembusu virus affects virus replication in vitro and contributes to the neurovirulence and pathogenicity in vivo
title_fullStr Glycosylation on envelope glycoprotein of duck Tembusu virus affects virus replication in vitro and contributes to the neurovirulence and pathogenicity in vivo
title_full_unstemmed Glycosylation on envelope glycoprotein of duck Tembusu virus affects virus replication in vitro and contributes to the neurovirulence and pathogenicity in vivo
title_short Glycosylation on envelope glycoprotein of duck Tembusu virus affects virus replication in vitro and contributes to the neurovirulence and pathogenicity in vivo
title_sort glycosylation on envelope glycoprotein of duck tembusu virus affects virus replication in vitro and contributes to the neurovirulence and pathogenicity in vivo
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437475/
https://www.ncbi.nlm.nih.gov/pubmed/34506259
http://dx.doi.org/10.1080/21505594.2021.1974329
work_keys_str_mv AT liudejian glycosylationonenvelopeglycoproteinofducktembusuvirusaffectsvirusreplicationinvitroandcontributestotheneurovirulenceandpathogenicityinvivo
AT xiaoxuyao glycosylationonenvelopeglycoproteinofducktembusuvirusaffectsvirusreplicationinvitroandcontributestotheneurovirulenceandpathogenicityinvivo
AT zhoupeng glycosylationonenvelopeglycoproteinofducktembusuvirusaffectsvirusreplicationinvitroandcontributestotheneurovirulenceandpathogenicityinvivo
AT zhenghuijun glycosylationonenvelopeglycoproteinofducktembusuvirusaffectsvirusreplicationinvitroandcontributestotheneurovirulenceandpathogenicityinvivo
AT liyaqian glycosylationonenvelopeglycoproteinofducktembusuvirusaffectsvirusreplicationinvitroandcontributestotheneurovirulenceandpathogenicityinvivo
AT jinhui glycosylationonenvelopeglycoproteinofducktembusuvirusaffectsvirusreplicationinvitroandcontributestotheneurovirulenceandpathogenicityinvivo
AT jongkaewwattanaanan glycosylationonenvelopeglycoproteinofducktembusuvirusaffectsvirusreplicationinvitroandcontributestotheneurovirulenceandpathogenicityinvivo
AT luorui glycosylationonenvelopeglycoproteinofducktembusuvirusaffectsvirusreplicationinvitroandcontributestotheneurovirulenceandpathogenicityinvivo