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

John Devincenzo, Tom Wilkinson, Akshay Vaishnaw, Jeff Cehelsky, Rachel Meyers, Saraswathy Nochur, Lisa Harrison, Patricia Meeking, Alex Mann, Elizabeth Moane, John Oxford, Rajat Pareek, Ryves Moore, Ed Walsh, Robert Studholme, Preston Dorsett, Rene Alvarez, Robert Lambkin-Williams

Research output: Contribution to journalArticle

160 Citations (Scopus)

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 a human experimental wild-type RSV infection model to address these challenges. Methods: Healthy volunteers (n = 35), in five cohorts, received increasing quantities (3.0-5.4 log plaque-forming units/person) of wild-type RSV-A intranasally. Measurements and Main 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. Symptoms began 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 disease measurements (symptoms, physical examination, and amount of nasal mucus). Conclusions: Viralload appears todrive disease manifestations in humans 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.

Original languageEnglish (US)
Pages (from-to)1305-1314
Number of pages10
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume182
Issue number10
DOIs
StatePublished - Nov 15 2010

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Respiratory Syncytial Viruses
Viral Load
Respiratory Syncytial Virus Infections
Virus Diseases
Antiviral Agents
Human respiratory syncytial virus
Immune System Diseases
Human Development
Mucus
Interleukin-8
Nose
Respiratory Tract Infections
Physical Examination
Drive
Real-Time Polymerase Chain Reaction
Volunteers
Interleukin-6
Healthy Volunteers
Pediatrics
Cytokines

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Viral load drives disease in humans experimentally infected with respiratory syncytial virus. / Devincenzo, John; Wilkinson, Tom; 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; Lambkin-Williams, Robert.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 182, No. 10, 15.11.2010, p. 1305-1314.

Research output: Contribution to journalArticle

Devincenzo, J, Wilkinson, T, Vaishnaw, A, Cehelsky, J, Meyers, R, Nochur, S, Harrison, L, Meeking, P, Mann, A, Moane, E, Oxford, J, Pareek, R, Moore, R, Walsh, E, Studholme, R, Dorsett, P, Alvarez, R & Lambkin-Williams, R 2010, 'Viral load drives disease in humans experimentally infected with respiratory syncytial virus', American Journal of Respiratory and Critical Care Medicine, vol. 182, no. 10, pp. 1305-1314. https://doi.org/10.1164/rccm.201002-0221OC
Devincenzo, John ; Wilkinson, Tom ; 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 ; Lambkin-Williams, Robert. / Viral load drives disease in humans experimentally infected with respiratory syncytial virus. In: American Journal of Respiratory and Critical Care Medicine. 2010 ; Vol. 182, No. 10. pp. 1305-1314.
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AU - Nochur, Saraswathy

AU - Harrison, Lisa

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AU - Moane, Elizabeth

AU - Oxford, John

AU - Pareek, Rajat

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