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Viral load drives disease in humans experimentally infected with respiratory syncytial virus

DeVincenzo, John P., Wilkinson, Tom M.A., Vaishnaw, Akshay, Cehelsky, Jeff, Meyers, Rachel, Nochur, Saraswathy, Harrison, Lisa, Meeking, Patricia, Mann, Alex, Moane, Elizabeth, Oxford, John, Pareek, Rajat, Moore, Ryves, Walsh, Ed, Studholme, Robert, Dorsett, Preston, Alvarez, Rene and Lambkin-Williams, Robert (2010) Viral load drives disease in humans experimentally infected with respiratory syncytial virus American Journal of Respiratory and Critical Care Medicine, 182, (10), pp. 1305-1314. (doi:10.1164/rccm.201002-0221OC). (PMID:20622030).

Record type: Article

Abstract

Rationale: Respiratory syncytial virus (RSV) is the leading cause of
childhood lower respiratory infection, yet viable therapies are
lacking. Two major challenges have stalled antiviral development:
ethical difficulties in performing pediatric proof-of-concept studies
and the prevailing concept that the disease is immune-mediated
rather than being driven by viral load.
Objectives: The development of ahumanexperimental wild-type RSV
infection model to address these challenges.
Methods: Healthy volunteers (n 5 35), in five cohorts, received
increasing quantities (3.0–5.4 log plaque-forming units/person) of
wild-type RSV-A intranasally.
Measurements andMain Results: Overall, 77%of volunteers consistently
shed virus. Infection rate, viral loads, disease severity, and safety were
similar between cohorts and were unrelated to quantity of RSV received.
Symptomsbegan near the time of initial viral detection, peaked
in severity near when viral load peaked, and subsided as viral loads
(measured by real-time polymerase chain reaction) slowly declined.
Viral loads correlated significantly with intranasal proinflammatory
cytokine concentrations (IL-6 and IL-8). Increased viral load correlated
consistently with increases inmultiple different diseasemeasurements
(symptoms, physical examination, and amount of nasal mucus).
Conclusions:Viralloadappears todrive diseasemanifestations inhumans
with RSV infection. The observed parallel viral and disease kinetics
support a potential clinical benefit of RSV antivirals. This reproducible
model facilitates the development of future RSV therapeutics.

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More information

Published date: 15 November 2010
Keywords: RSV, pneumonia, bronchiolitis, pathogenesis, viral load
Organisations: Infection Inflammation & Immunity

Identifiers

Local EPrints ID: 185925
URI: http://eprints.soton.ac.uk/id/eprint/185925
ISSN: 1073-449X
PURE UUID: 302873cb-a0b4-4cc8-a7ac-86dd46373a0e

Catalogue record

Date deposited: 11 May 2011 11:42
Last modified: 04 Jul 2017 16:58

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Contributors

Author: John P. DeVincenzo
Author: Akshay Vaishnaw
Author: Jeff Cehelsky
Author: Rachel Meyers
Author: Saraswathy Nochur
Author: Lisa Harrison
Author: Patricia Meeking
Author: Alex Mann
Author: Elizabeth Moane
Author: John Oxford
Author: Rajat Pareek
Author: Ryves Moore
Author: Ed Walsh
Author: Robert Studholme
Author: Preston Dorsett
Author: Rene Alvarez
Author: Robert Lambkin-Williams

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