Detection of respiratory syncytial virus defective genomes in nasal secretions is associated with distinct clinical outcomes.
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
30
04
2020
accepted:
23
02
2021
pubmed:
3
4
2021
medline:
1
9
2021
entrez:
2
4
2021
Statut:
ppublish
Résumé
Respiratory syncytial virus (RSV) causes respiratory illness in children, immunosuppressed individuals and the elderly. However, the viral factors influencing the clinical outcome of RSV infections remain poorly defined. Defective viral genomes (DVGs) can suppress virus replication by competing for viral proteins and by stimulating antiviral immunity. We studied the association between detection of DVGs of the copy-back type and disease severity in three RSV A-confirmed cohorts. In hospitalized children, detection of DVGs in respiratory samples at or around the time of admission associated strongly with more severe disease, higher viral load and a stronger pro-inflammatory response. Interestingly, in experimentally infected adults, the presence of DVGs in respiratory secretions differentially associated with RSV disease severity depending on when DVGs were detected. Detection of DVGs early after infection associated with low viral loads and mild disease, whereas detection of DVGs late after infection, especially if DVGs were present for prolonged periods, associated with high viral loads and severe disease. Taken together, we demonstrate that the kinetics of DVG accumulation and duration could predict clinical outcome of RSV A infection in humans, and thus could be used as a prognostic tool to identify patients at risk of worse clinical disease.
Identifiants
pubmed: 33795879
doi: 10.1038/s41564-021-00882-3
pii: 10.1038/s41564-021-00882-3
pmc: PMC9098209
mid: NIHMS1691560
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
672-681Subventions
Organisme : NIAID NIH HHS
ID : K24 AI077930
Pays : United States
Organisme : Wellcome Trust
ID : 087805/Z/08/Z
Pays : United Kingdom
Organisme : NCRR NIH HHS
ID : TL1 RR024978
Pays : United States
Organisme : Medical Research Council
ID : G0902266
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI137062
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI095227
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI134862
Pays : United States
Organisme : NHLBI NIH HHS
ID : K01 HL149989
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024975
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
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