NS5-V372A and NS5-H386Y variations are responsible for differences in interferon α/β induction and co-contribute to the replication advantage of Japanese encephalitis virus genotype I over genotype III in ducklings.
Animals
Antiviral Agents
/ pharmacology
Ducks
Encephalitis Virus, Japanese
/ drug effects
Encephalitis, Japanese
/ drug therapy
Host-Pathogen Interactions
Interferon-alpha
/ pharmacology
Interferon-beta
/ pharmacology
Mice
Mutation
Protein Binding
Swine
Viral Nonstructural Proteins
/ genetics
Virus Replication
/ drug effects
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
29
02
2020
accepted:
01
07
2020
revised:
16
09
2020
pubmed:
4
9
2020
medline:
22
10
2020
entrez:
4
9
2020
Statut:
epublish
Résumé
Japanese encephalitis virus (JEV) genotype I (GI) replicates more efficiently than genotype III (GIII) in birds, and this difference is considered to be one of the reasons for the JEV genotype shift. In this study, we utilized duck embryo fibroblasts and domestic ducklings as in vitro and in vivo models of a JEV amplifying avian host to identify the viral determinants of the differing replication efficiency between the GI and GIII strains in birds. GI strains induced significantly lower levels of interferon (IFN)-α and β production than GIII strains, an effect orrelated with the enhanced replication efficiency of GI strains over GIII strains. By using a series of chimeric viruses with exchange of viral structural and non-structural (NS) proteins, we identified NS5 as the viral determinant of the differences in IFN-α and β induction and replication efficiency between the GI and III strains. NS5 inhibited IFN-α and β production induced by poly(I:C) stimulation and harbored 11 amino acid variations, of which the NS5-V372A and NS5-H386Y variations were identified to co-contribute to the differences in IFN-α and β induction and replication efficiency between the strains. The NS5-V372A and NS5-H386Y variations resulted in alterations in the number of hydrogen bonds formed with neighboring residues, which were associated with the different ability of the GI and GIII strains to inhibit IFN-α and β production. Our findings indicated that the NS5-V372A and NS5-H386Y variations enabled GI strains to inhibit IFN-α and β production more efficiently than GIII strains for antagonism of the IFN-I mediated antiviral response, thereby leading to the replication and host adaption advantages of GI strains over GIII strains in birds. These findings provide new insight into the molecular basis of the JEV genotype shift.
Identifiants
pubmed: 32881988
doi: 10.1371/journal.ppat.1008773
pii: PPATHOGENS-D-20-00408
pmc: PMC7494076
doi:
Substances chimiques
Antiviral Agents
0
Interferon-alpha
0
Viral Nonstructural Proteins
0
Interferon-beta
77238-31-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008773Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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