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About:
Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication
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wasabi.inria.fr
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Academic Article
research paper
schema:ScholarlyArticle
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type
Academic Article
research paper
schema:ScholarlyArticle
isDefinedBy
Covid-on-the-Web dataset
has title
Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication
Creator
Kehn-Hall, Kylene
Lundberg, Lindsay
Pinkham, Chelsea
Bell, Todd
Brahms, Ashwini
Woodson, Caitlin
Bailey, Charles
Espina, Virginia
Carey, Brian
Lin,
Liotta, Lance
Dahal,
De La Fuente, Cynthia
Id, Bibha
Id, Shih-Chao
Source
Medline; PMC
abstract
Viruses must parasitize host cell translational machinery in order to make proteins for viral progeny. In this study, we sought to use this signal transduction conduit against them by inhibiting multiple kinases that influence translation. Previous work indicated that several kinases involved in translation, including p70 S6K, p90RSK, ERK, and p38 MAPK, are phosphorylated following Rift Valley fever virus (RVFV) infection. Furthermore, inhibiting p70 S6K through treatment with the FDA approved drug rapamycin prevents RVFV pathogenesis in a mouse model of infection. We hypothesized that inhibiting either p70 S6K, p90RSK, or p90RSK’s upstream kinases, ERK and p38 MAPK, would decrease translation and subsequent viral replication. Treatment with the p70 S6K inhibitor PF-4708671 resulted in decreased phosphorylation of translational proteins and reduced RVFV titers. In contrast, treatment with the p90RSK inhibitor BI-D1870, p38MAPK inhibitor SB203580, or the ERK inhibitor PD0325901 alone had minimal influence on RVFV titers. The combination of PF-4708671 and BI-D1870 treatment resulted in robust inhibition of RVFV replication. Likewise, a synergistic inhibition of RVFV replication was observed with p38MAPK inhibitor SB203580 or the ERK inhibitor PD0325901 combined with rapamycin treatment. These findings serve as a proof of concept regarding combination kinase inhibitor treatment for RVFV infection.
has issue date
2018-04-13
(
xsd:dateTime
)
bibo:doi
10.3390/v10040191
bibo:pmid
29652799
has license
cc-by
sha1sum (hex)
369914e87f682579eb3a5efeb43dc0184a88b5d6
schema:url
https://doi.org/10.3390/v10040191
resource representing a document's title
Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication
has PubMed Central identifier
PMC5923485
has PubMed identifier
29652799
schema:publication
Viruses
resource representing a document's body
covid:369914e87f682579eb3a5efeb43dc0184a88b5d6#body_text
is
schema:about
of
named entity 'ERK'
named entity 'rapamycin'
named entity 'reduced'
named entity 'translation'
covid:arg/369914e87f682579eb3a5efeb43dc0184a88b5d6
named entity 'combination'
named entity 'p90RSK'
named entity 'machinery'
named entity 'S6K'
named entity 'S6K'
named entity 'replication'
named entity 'replication'
named entity 'Rift Valley'
named entity 'viral'
named entity 'signal transduction'
named entity 'parasitize'
named entity 'inhibition'
named entity 'study'
named entity 'p90RSK'
named entity 'Viruses'
named entity 'pathogenesis'
named entity 'RVFV'
named entity 'approved drug'
named entity 'p70 S6K'
named entity 'RVFV'
named entity 'infection'
named entity 'Rift Valley fever virus'
named entity 'RVFV'
named entity 'p90RSK'
named entity 'kinases'
named entity 'RVFV'
named entity 'Kinase Inhibitor'
named entity 'cell'
named entity 'homeostasis'
named entity 'La Jolla'
named entity 'RVFV'
named entity 'chemotherapy'
named entity 'supernatants'
named entity 'RVFV'
named entity 'SB203580'
named entity 'p90RSK'
named entity 'kinase'
named entity 'kinase'
named entity 'ATCC'
named entity 'rapamycin'
named entity 'phosphorylation'
named entity 'rapamycin'
named entity 'p90RSK'
named entity 'p38 MAPK'
named entity 'RVFV'
named entity 'ribosomal protein'
named entity 'Phosphorylation'
named entity 'ATCC'
named entity 'RVFV'
named entity 'hepatitis viruses'
named entity 'Rapamycin'
named entity 'gene'
named entity 'p38 MAPK'
named entity 'actin'
named entity 'ribosomal protein'
named entity 'hepatocyte'
named entity 'SB203580'
named entity 'kinase'
named entity 'p90RSK'
named entity 'carboxy-terminal'
named entity 'chemotherapy'
named entity 'MOI'
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