Splicing-Dependent Subcellular Targeting of Borna Disease Virus Nucleoprotein Isoforms.
Alternative Splicing
/ genetics
Animals
Base Sequence
Borna Disease
/ virology
Borna disease virus
/ genetics
Cell Line
Cell Nucleus
/ virology
Chlorocebus aethiops
HEK293 Cells
Humans
Molecular Dynamics Simulation
Nucleoproteins
/ genetics
Protein Isoforms
/ genetics
RNA, Viral
/ genetics
Sequence Analysis, RNA
Vero Cells
Viral Proteins
/ genetics
Virus Replication
/ genetics
Mononegavirales
RNA splicing
bornavirus
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
01 03 2019
01 03 2019
Historique:
received:
14
09
2018
accepted:
14
11
2018
pubmed:
14
12
2018
medline:
21
11
2019
entrez:
14
12
2018
Statut:
epublish
Résumé
Targeting of viral proteins to specific subcellular compartments is a fundamental step for viruses to achieve successful replication in infected cells. Borna disease virus 1 (BoDV-1), a nonsegmented, negative-strand RNA virus, uniquely replicates and persists in the cell nucleus. Here, it is demonstrated that BoDV nucleoprotein (N) transcripts undergo mRNA splicing to generate truncated isoforms. In combination with alternative usage of translation initiation sites, the N gene potentially expresses at least six different isoforms, which exhibit diverse intracellular localizations, including the nucleoplasm, cytoplasm, and endoplasmic reticulum (ER), as well as intranuclear viral replication sites. Interestingly, the ER-targeting signal peptide in N is exposed by removing the intron by mRNA splicing. Furthermore, the spliced isoforms inhibit viral polymerase activity. Consistently, recombinant BoDVs lacking the N-splicing signals acquire the ability to replicate faster than wild-type virus in cultured cells, suggesting that N isoforms created by mRNA splicing negatively regulate BoDV replication. These results provided not only the mechanism of how mRNA splicing generates viral proteins that have distinct functions but also a novel strategy for replication control of RNA viruses using isoforms with different subcellular localizations.
Identifiants
pubmed: 30541858
pii: JVI.01621-18
doi: 10.1128/JVI.01621-18
pmc: PMC6384089
pii:
doi:
Substances chimiques
Nucleoproteins
0
Protein Isoforms
0
RNA, Viral
0
Viral Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2019 American Society for Microbiology.
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