Role of NS1 and TLR3 in Pathogenesis and Immunity of WNV.
Animals
Antibodies, Neutralizing
/ metabolism
Antibodies, Viral
/ immunology
Brain
/ immunology
Cell Line
Cytokines
/ blood
Disease Models, Animal
Female
Immunity
Immunization
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Toll-Like Receptor 3
/ genetics
Vaccines, Subunit
Viral Nonstructural Proteins
/ genetics
Viral Vaccines
Virus Replication
West Nile Fever
/ immunology
West Nile virus
/ genetics
NS1
TLR3
West Nile Virus
West Nile neuroinvasive disease
immunity
pathogenesis
subunit vaccine
Journal
Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722
Informations de publication
Date de publication:
03 07 2019
03 07 2019
Historique:
received:
01
05
2019
revised:
28
06
2019
accepted:
29
06
2019
entrez:
7
7
2019
pubmed:
7
7
2019
medline:
2
9
2020
Statut:
epublish
Résumé
West Nile Virus (WNV) is a mosquito-transmitted flavivirus which causes encephalitis especially in elderly and immunocompromised individuals. Previous studies have suggested the protective role of the Toll-like receptor 3 (TLR3) pathway against WNV entry into the brain, while the WNV non-structural protein 1 (NS1) interferes with the TLR3 signaling pathway, besides being a component of viral genome replication machinery. In this study, we investigated whether immunization with NS1 could protect against WNV neuroinvasion in the context of TLR3 deficiency. We immunized mice with either an intact or deleted TLR3 system (TLR3KO) with WNV envelope glycoprotein (gE) protein, NS1, or a combination of gE and NS1. Immunization with gE or gE/NS1, but not with NS1 alone, induced WNV neutralizing antibodies and protected against WNV brain invasion and inflammation. The presence of intact TLR3 signaling had no apparent effect on WNV brain invasion. However, mock-immunized TLR3KO mice had higher inflammatory cell invasion upon WNV brain infection than NS1-immunized TLR3KO mice and wild type mice. Thus, immunization against NS1 may reduce brain inflammation in a context of TLR3 signaling deficiency.
Identifiants
pubmed: 31277274
pii: v11070603
doi: 10.3390/v11070603
pmc: PMC6669597
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Cytokines
0
TLR3 protein, mouse
0
Toll-Like Receptor 3
0
Vaccines, Subunit
0
Viral Nonstructural Proteins
0
Viral Vaccines
0
nonstructural protein 1, West Nile virus
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Swiss National Science Foundation
ID : 310030_166206
Pays : Switzerland
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