About: Molecular Chaperone Hsp90 Is a Therapeutic Target for Noroviruses

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An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Molecular Chaperone Hsp90 Is a Therapeutic Target for Noroviruses
Creator	Goodfellow, Ian Neyts, Johan Vashist, Surender Choi, Jayoung Hwang, Seungmin Rocha-Pereira, Joana De Rougemont, Alexis Wobus, Christiane Gonzalez-Hernandez, Mariam Urena, Luis
Source	PMC
abstract	Human noroviruses (HuNoV) are a significant cause of acute gastroenteritis in the developed world, and yet our understanding of the molecular pathways involved in norovirus replication and pathogenesis has been limited by the inability to efficiently culture these viruses in the laboratory. Using the murine norovirus (MNV) model, we have recently identified a network of host factors that interact with the 5′ and 3′ extremities of the norovirus RNA genome. In addition to a number of well-known cellular RNA binding proteins, the molecular chaperone Hsp90 was identified as a component of the ribonucleoprotein complex. Here, we show that the inhibition of Hsp90 activity negatively impacts norovirus replication in cell culture. Small-molecule-mediated inhibition of Hsp90 activity using 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin) revealed that Hsp90 plays a pleiotropic role in the norovirus life cycle but that the stability of the viral capsid protein is integrally linked to Hsp90 activity. Furthermore, we demonstrate that both the MNV-1 and the HuNoV capsid proteins require Hsp90 activity for their stability and that targeting Hsp90 in vivo can significantly reduce virus replication. In summary, we demonstrate that targeting cellular proteostasis can inhibit norovirus replication, identifying a potential novel therapeutic target for the treatment of norovirus infections. IMPORTANCE HuNoV are a major cause of acute gastroenteritis around the world. RNA viruses, including noroviruses, rely heavily on host cell proteins and pathways for all aspects of their life cycle. Here, we identify one such protein, the molecular chaperone Hsp90, as an important factor required during the norovirus life cycle. We demonstrate that both murine and human noroviruses require the activity of Hsp90 for the stability of their capsid proteins. Furthermore, we demonstrate that targeting Hsp90 activity in vivo using small molecule inhibitors also reduces infectious virus production. Given the considerable interest in the development of Hsp90 inhibitors for use in cancer therapeutics, we identify here a new target that could be explored for the development of antiviral strategies to control norovirus outbreaks and treat chronic norovirus infection in immunosuppressed patients.
has issue date	2015-04-08(xsd:dateTime)
bibo:doi	10.1128/jvi.00315-15
bibo:pmid	25855731
has license	cc-by
sha1sum (hex)	c715e7ac6f9be9ea6f0b80a6579c7a3426b41c1d
schema:url	https://doi.org/10.1128/jvi.00315-15
resource representing a document's title	Molecular Chaperone Hsp90 Is a Therapeutic Target for Noroviruses
has PubMed Central identifier	PMC4474317
has PubMed identifier	25855731
schema:publication	J Virol
resource representing a document's body	covid:c715e7ac6f9be9ea6f0b80a6579c7a3426b41c1d#body_text
is schema:about of	named entity 'culture' named entity 'gastroenteritis' named entity 'Hsp90' named entity 'MNV' named entity 'ROLE' named entity 'NETWORK' named entity 'MODEL' named entity 'LIFE CYCLE' named entity 'MOLECULAR CHAPERONE' named entity 'PROTEOSTASIS' named entity 'RNA GENOME' named entity 'REDUCE' named entity 'STABILITY' named entity 'REPLICATION' named entity 'PATHOGENESIS' named entity 'CELLULAR' named entity 'EXTREMITIES' named entity 'THEIR' named entity 'cell culture' named entity 'Hsp90' named entity 'vivo' named entity 'protein' named entity 'RNA' named entity 'pathways' named entity 'pathogenesis' named entity 'norovirus' named entity 'Hsp90' named entity 'inhibition' named entity 'interact' named entity 'norovirus' named entity 'virus replication' named entity 'developed world' named entity 'pathogenesis' named entity 'cell culture' named entity 'host factors' named entity 'life cycle' named entity 'Noroviruses' named entity 'Therapeutic Target' named entity 'replication' named entity '17-DMAG' named entity 'Promega' named entity 'virus' named entity 'RNA viruses' named entity 'Promega' named entity 'viral proteins' named entity 'genome' named entity '17-DMAG' named entity 'VP1' named entity 'affinity purification' named entity 'statistical significance' named entity 'transfected' named entity 'inoculum' named entity 'GAPDH' named entity 'Akt' named entity 'cellular component' named entity 'proteasome' named entity 'Small molecule inhibitors' named entity 'viral RNA' named entity 'Hsp90' named entity 'therapeutic target' named entity 'virus' named entity 'Renilla luciferase' named entity 'viruses' named entity 'virus' named entity 'protein translation' named entity 'bamboo mosaic virus' named entity 'protein' named entity 'norovirus' named entity 'Ni-NTA' named entity 'Nonstructural proteins' named entity '17-DMAG' named entity 'RNA transcripts'

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