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- Bindiya Bagga, L Harrison, P Roddam, and J P DeVincenzo.
- Department of Pediatrics, University of Tennessee Health Sciences Center, Memphis, TN, United States; LeBonheur Children's Hospital, Memphis, TN, United States; Children's Foundation Research Center, Memphis, TN, United States. Electronic address: bbagga@uthsc.edu.
- J. Clin. Virol. 2018 Sep 1; 106: 1-6.
BackgroundRespiratory symptoms in RSV persist long after the virus is no longer detected by culture. Current concepts of RSV pathogenesis explain this by RSV inducing a long-lasting pathogenic immune cascade. We alternatively hypothesized that prolonged unrecognized RSV replication may be responsible and studied this possibility directly in a human wild-type RSV experimental infection model.ObjectiveThe objective of the current report was to define the duration of true human RSV replication by studying it directly in immunocompetent adults experimentally infected with a clinical strain of RSV utilizing this previously established safe and reproducible model.Study Design35 healthy adult volunteers were inoculated with RSV-A (Memphis-37, a low11 passage clinical strain virus, manufactured from a hospitalized bronchiolitic infant) and evaluated over 12 days. Viral load by culture, parallel quantitative PCR (genomic, message) and RSV-specific IgA, were measured twice daily from serially collected nasal washes.ResultsAfter inoculation, 77% (27/35) of volunteers became RSV infected. As expected, culture-detectable RSV ceased abruptly by the 5-6 t h 15 infection day. However, infected volunteers demonstrated prolonged RSV presence by both genomic and message PCR. RSV-specific IgA rose within respiratory secretions of infected volunteers during same time frame.ConclusionsRSV replication appears to continue in humans far longer than previously thought. The rise in nasal RSV-specific IgA shortly after infection likely neutralizes culture detectable virus producing misleadingly short durations of infection. Prolonged viral replication helps explain RSV's extended disease manifestations and increases the potential utility of antivirals.Copyright © 2018 Elsevier B.V. All rights reserved.
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