About: Selective Packaging in Murine Coronavirus Promotes Virulence by Limiting Type I Interferon Responses

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

Attributes	Values
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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