Detection of respiratory syncytial virus defective genomes in nasal secretions is associated with distinct clinical outcomes.

TitleDetection of respiratory syncytial virus defective genomes in nasal secretions is associated with distinct clinical outcomes.
Publication TypeJournal Article
Year of Publication2021
AuthorsFelt SA, Sun Y, Jozwik A, Paras A, Habibi MS, Nickle D, Anderson L, Achouri E, Feemster KA, Cárdenas AMaría, Turi KN, Chang M, Hartert TV, Sengupta S, Chiu C, López CB
JournalNat Microbiol
Date Published2021 Apr 01
ISSN2058-5276
Abstract

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.

DOI10.1038/s41564-021-00882-3
Alternate JournalNat Microbiol
PubMed ID33795879
Grant ListAI095227 / / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) /
AI077930 / / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) /
RR024975 / / U.S. Department of Health & Human Services | NIH | National Center for Research Resources (NCRR) /
G0902266 / / RCUK | Medical Research Council (MRC) /
087805/Z/08/Z / / Wellcome Trust (Wellcome) /
AI137092 / / Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) /
AI137062 / / Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) /