Heat Shock Protein 90 Ensures the Integrity of Rubella Virus p150 Protein and Supports Viral Replication.
A549 Cells
Animals
Cell Line
Chlorocebus aethiops
HEK293 Cells
HSP90 Heat-Shock Proteins
/ metabolism
Humans
Molecular Chaperones
/ metabolism
Proteolysis
RNA, Viral
/ genetics
RNA-Dependent RNA Polymerase
/ genetics
Rubella
/ virology
Rubella virus
/ metabolism
Vero Cells
Viral Nonstructural Proteins
/ genetics
Virus Replication
/ genetics
HSP90
Matonaviridae
Togaviridae
alphavirus
genome replication
host factor
rubella virus
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
15 11 2019
15 11 2019
Historique:
received:
13
07
2019
accepted:
21
08
2019
pubmed:
6
9
2019
medline:
21
7
2020
entrez:
6
9
2019
Statut:
epublish
Résumé
Two viral nonstructural proteins, p150 and p90, are expressed in rubella virus (RUBV)-infected cells and mediate viral genome replication, presumably using various host machineries. Molecular chaperones are critical host factors for the maintenance of cellular proteostasis, and certain viral proteins use this chaperone system. The RUBV p150 and p90 proteins are generated from a precursor polyprotein, p200, via processing by the protease activity of its p150 region. This processing is essential for RUBV genome replication. Here we show that heat shock protein 90 (HSP90), a molecular chaperone, is an important host factor for RUBV genome replication. The treatment of RUBV-infected cells with the HSP90 inhibitors 17-allylamino-17-desmethoxygeldanamycin (17-AAG) and ganetespib suppressed RUBV genome replication. HSP90α physically interacted with p150, but not p90. Further analyses into the mechanism of action of the HSP90 inhibitors revealed that HSP90 activity contributes to p150 functional integrity and promotes p200 processing. Collectively, our data demonstrate that RUBV p150 is a client of the HSP90 molecular chaperone and that HSP90 functions as a key host factor for RUBV replication.
Identifiants
pubmed: 31484751
pii: JVI.01142-19
doi: 10.1128/JVI.01142-19
pmc: PMC6819934
pii:
doi:
Substances chimiques
HSP90 Heat-Shock Proteins
0
Molecular Chaperones
0
RNA, Viral
0
Viral Nonstructural Proteins
0
RNA-Dependent RNA Polymerase
EC 2.7.7.48
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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