About: Viral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral Isolation

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About: Viral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral Isolation Goto Sponge NotDistinct Permalink

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

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Viral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral Isolation
Creator	Iketani, Sho Mathieu, Cyrille Moscona, Anne Porotto, Matteo Makhsous, Negar Greninger, Alexander Ferren, Marion Rima, Bert Aquino, Dolly Georges, Amedee Des Shean, Ryan
Source	PMC
abstract	Human parainfluenza viruses cause a large burden of human respiratory illness. While much research relies upon viruses grown in cultured immortalized cells, human parainfluenza virus 3 (HPIV-3) evolves in culture. Cultured viruses differ in their properties compared to clinical strains. We present a genome-wide survey of HPIV-3 adaptations to culture using metagenomic next-generation sequencing of matched pairs of clinical samples and primary culture isolates (zero passage virus). Nonsynonymous changes arose during primary viral isolation, almost entirely in the genes encoding the two surface glycoproteins—the receptor binding protein hemagglutinin-neuraminidase (HN) or the fusion protein (F). We recovered genomes from 95 HPIV-3 primary culture isolates and 23 HPIV-3 strains directly from clinical samples. HN mutations arising during primary viral isolation resulted in substitutions at HN’s dimerization/F-interaction site, a site critical for activation of viral fusion. Alterations in HN dimer interface residues known to favor infection in culture occurred within 4 days (H552 and N556). A novel cluster of residues at a different face of the HN dimer interface emerged (P241 and R242) and imply a role in HPIV-3-mediated fusion. Functional characterization of these culture-associated HN mutations in a clinical isolate background revealed acquisition of the fusogenic phenotype associated with cultured HPIV-3; the HN-F complex showed enhanced fusion and decreased receptor-cleaving activity. These results utilize a method for identifying genome-wide changes associated with brief adaptation to culture to highlight the notion that even brief exposure to immortalized cells may affect key viral properties and underscore the balance of features of the HN-F complex required for fitness by circulating viruses.
has issue date	2018-07-03(xsd:dateTime)
bibo:doi	10.1128/mbio.00898-18
bibo:pmid	29970463
has license	cc-by
sha1sum (hex)	7f8715a818bfd325bf4413d3c07003d7ce7b6f7e
schema:url	https://doi.org/10.1128/mbio.00898-18
resource representing a document's title	Viral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral Isolation
has PubMed Central identifier	PMC6030562
has PubMed identifier	29970463
schema:publication	mBio
resource representing a document's body	covid:7f8715a818bfd325bf4413d3c07003d7ce7b6f7e#body_text
is schema:about of	named entity 'activation' named entity 'While' named entity 'evolves' named entity 'primary' named entity 'notion' named entity 'neuraminidase' named entity 'isolates' named entity 'positive' named entity 'fusion' named entity 'face' named entity 'viruses' named entity 'MORBIDITY AND MORTALITY' named entity 'CULTURE' named entity 'DECREASED' named entity 'ACTIVITY' named entity 'DEEP' named entity 'RECEPTOR BINDING' named entity 'GENOMIC SEQUENCING' named entity 'NEURAMINIDASE ACTIVITY' named entity 'MUTATIONS' named entity 'RAPID' named entity 'VOLUME' named entity 'KNOWN' named entity 'VIRAL ISOLATION' named entity 'ISOLATES' named entity 'THEIR' named entity 'HUMANS' named entity 'METHOD' named entity 'ACTIVATION' named entity 'KEY' covid:arg/7f8715a818bfd325bf4413d3c07003d7ce7b6f7e named entity 'GENOMIC' named entity 'THESE' named entity '27S' named entity 'MUCH' named entity 'REVEALED' named entity 'IDENTIFYING' named entity 'RAPID' named entity 'AFFECT' named entity 'INCREASING' named entity 'BRIEF' named entity 'ASSOCIATED' named entity 'ENGAGEMENT' named entity 'RESPIRATORY ILLNESS' named entity 'VIRUS' named entity 'ALTERATIONS' named entity 'FEATURES' named entity 'CLUSTER' named entity 'RESULTS' named entity 'CELLS' named entity 'FAVOR' named entity 'CHANGES' named entity 'BINDING PROTEIN' named entity 'GENOMES' named entity 'DIRECTLY' named entity 'DECREASING' named entity 'LOST' named entity 'VIRAL ISOLATION' named entity 'FITNESS' named entity 'REQUIRED' named entity 'HUMANS' named entity 'PROPERTIES' named entity 'VIRUSES' named entity 'ASSOCIATED WITH' named entity 'ASM' named entity 'COMPARED' named entity 'CUL' named entity 'PROTEIN ' named entity 'FUNCTION' named entity 'DIMER' named entity 'RECEPTOR'

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