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), 1305-1314. (doi:10.1164/rccm.201002-0221OC). (PMID:20622030)

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.

This record has no associated files available for download.

Contributors

Download statistics