Inhibition of HIF-1α accumulation in prostate cancer cells is initiated during early stages of mammalian orthoreovirus infection.
HIF-1α
Hypoxia
Mammalian orthoreovirus
Prostate cancer
UV-inactivation
Journal
Virology
ISSN: 1096-0341
Titre abrégé: Virology
Pays: United States
ID NLM: 0110674
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
02
09
2020
revised:
22
02
2021
accepted:
23
02
2021
pubmed:
16
3
2021
medline:
29
12
2021
entrez:
15
3
2021
Statut:
ppublish
Résumé
Mammalian orthoreovirus (MRV) is a safe and effective cancer killing virus that has completed Phase I-III clinical trials against numerous cancer types. While many patients experience benefit from MRV therapy, pre-defined set points necessary for FDA approval have not been reached. Therefore, additional research into MRV biology and the effect of viral therapy on different tumor genetic subtypes and microenvironments is necessary to identify tumors most amenable to MRV virotherapy. In this work we analyzed the stage of viral infection necessary to inhibit HIF-1α, an aggressive cancer activator induced by hypoxia. We demonstrated that two viral capsid proteins were not necessary and that a step parallel with virus core movement across the endosomal membrane was required for this inhibition. Altogether, this work clarifies the mechanisms of MRV-induced HIF-1α inhibition and provides biological relevance for using MRV to inhibit the devastating effects of tumor hypoxia.
Identifiants
pubmed: 33721728
pii: S0042-6822(21)00054-4
doi: 10.1016/j.virol.2021.02.014
pmc: PMC8054447
mid: NIHMS1685478
pii:
doi:
Substances chimiques
HIF1A protein, human
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
38-48Subventions
Organisme : NCI NIH HHS
ID : R15 CA202984
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
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