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About:
Selective Packaging in Murine Coronavirus Promotes Virulence by Limiting Type I Interferon Responses
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wasabi.inria.fr
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Type:
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
Selective Packaging in Murine Coronavirus Promotes Virulence by Limiting Type I Interferon Responses
Creator
Gale, Michael
Perlman, Stanley
Aldabeeb, Dana
Athmer, Jeremiah
Channappanavar, Rudragouda
Grunewald, Matthew
Qu, Wen
Sekine, Aimee
Denison, Mark
Fehr, Anthony
Graepel, Kevin
Wheeler, D
Source
Medline; PMC
abstract
Selective packaging is a mechanism used by multiple virus families to specifically incorporate genomic RNA (gRNA) into virions and exclude other types of RNA. Lineage A betacoronaviruses incorporate a 95-bp stem-loop structure, the packaging signal (PS), into the nsp15 locus of ORF1b that is both necessary and sufficient for the packaging of RNAs. However, unlike other viral PSs, where mutations generally resulted in viral replication defects, mutation of the coronavirus (CoV) PS results in large increases in subgenomic RNA packaging with minimal effects on gRNA packaging in vitro and on viral titers. Here, we show that selective packaging is also required for viral evasion of the innate immune response and optimal pathogenicity. We engineered two distinct PS mutants in two different strains of murine hepatitis virus (MHV) that packaged increased levels of subgenomic RNAs, negative-sense genomic RNA, and even cellular RNAs. All PS mutant viruses replicated normally in vitro but caused dramatically reduced lethality and weight loss in vivo. PS mutant virus infection of bone marrow-derived macrophages resulted in increased interferon (IFN) production, indicating that the innate immune system limited the replication and/or pathogenesis of PS mutant viruses in vivo. PS mutant viruses remained attenuated in MAVS(−/−) and Toll-like receptor 7-knockout (TLR7(−/−)) mice, two well-known RNA sensors for CoVs, but virulence was restored in interferon alpha/beta receptor-knockout (IFNAR(−/−)) mice or in MAVS(−/−) mice treated with IFNAR-blocking antibodies. Together, these data indicate that coronaviruses promote virulence by utilizing selective packaging to avoid innate immune detection.
has issue date
2018-05-01
(
xsd:dateTime
)
bibo:doi
10.1128/mbio.00272-18
bibo:pmid
29717007
has license
cc-by
sha1sum (hex)
c7e5e64683c8dbf4d6585fd231d20a4d8ee3885e
schema:url
https://doi.org/10.1128/mbio.00272-18
resource representing a document's title
Selective Packaging in Murine Coronavirus Promotes Virulence by Limiting Type I Interferon Responses
has PubMed Central identifier
PMC5930304
has PubMed identifier
29717007
schema:publication
mBio
resource representing a document's body
covid:c7e5e64683c8dbf4d6585fd231d20a4d8ee3885e#body_text
is
schema:about
of
named entity 'virus'
named entity 'clear'
named entity 'gRNA'
named entity 'packaging'
named entity 'pathogenesis'
named entity 'leads'
named entity 'packaging'
named entity 'viral'
named entity 'interferon'
named entity 'loss'
named entity 'defects'
named entity 'packaging'
named entity 'Responses'
named entity 'Virulence'
named entity 'TYPE I INTERFERON'
named entity 'INCLUDING'
named entity 'AFFECT'
named entity 'GENERALLY'
named entity 'PSS'
named entity 'FAMILIES'
named entity 'STEM-LOOP STRUCTURE'
named entity 'RNA'
named entity 'MUTANT'
named entity 'ENGINEERED'
named entity 'CELLULAR'
named entity 'MOLECULES'
named entity 'BONE MARROW'
named entity 'GRNA'
named entity 'PROMOTE'
named entity 'LEVELS'
named entity 'TO AVOID'
named entity 'BUT'
named entity 'ATTENUATED'
named entity 'IFNAR'
named entity 'MACROPHAGES'
named entity 'MUTATIONS'
named entity 'PRODUCE'
named entity 'IS A'
named entity 'LETHALITY'
named entity 'EFFECTS'
named entity 'INNATE IMMUNE RESPONSE'
named entity 'EXCLUDE'
named entity 'INTERFERON SIGNALING'
named entity 'DISTINCT'
named entity 'IN VITRO'
named entity 'INCREASES'
named entity 'DATA'
named entity 'STRAINS'
named entity 'SUFFICIENT'
named entity 'MINIMAL'
named entity 'MULTIPLE'
named entity 'MECHANISM'
named entity 'INDICATING'
named entity 'BETACORONAVIRUSES'
named entity 'INCREASED'
named entity 'LIMITED'
named entity 'VIRAL REPLICATION'
named entity 'CLEAR'
named entity 'DOES NOT'
named entity 'PRODUCTION'
named entity 'IMMUNE'
named entity 'THEIR'
named entity 'NEGATIVE'
named entity 'KNOWN'
named entity 'RECEPTOR'
named entity 'VIRIONS'
named entity 'SENSE'
named entity 'PATHOGENICITY'
named entity 'NECESSARY'
named entity 'MURINE HEPATITIS VIRUS'
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