期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 182, 期 10, 页码 1305-1314出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.201002-0221OC
关键词
RSV; pneumonia; bronchiolifis; pathogenesis; viral load
资金
- NIH [RR 16187]
- National Center for Research Resources
- Children s Foundation Research Center of Memphis
- University of Tennessee General Clinical Research Center (GCRC) [UHPHS RR00211]
- Le Bonheur Foundation
- Alnylam Pharma ceuticals Cambridge MA
Rationale. Respiratory,syncytial virus (RSV) is the leading cause of childhood lower respiratory infection, yet viable therapies are lacking Two major challenges h we 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 seventy 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 in multiple different disease measurements (symptoms, physical examination, and amount of nasal mucus) Conclusions Viral load appears to drive 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
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