Role of CCL5 (RANTES) in Viral Lung Disease
Abstract
CCL5/RANTES is a key proinflammatory chemokine produced by virus-infected epithelial cells and present in respiratory secretions of asthmatics. To examine the role of CCL5 in viral lung disease, we measured its production during primary respiratory syncytial virus (RSV) infection and during secondary infection after sensitizing vaccination that induces Th2-mediated eosinophilia. A first peak of CCL5 mRNA and protein production was seen at 18 to 24 h of RSV infection, before significant lymphocyte recruitment occurred. Treatment in vivo with Met-RANTES (a competitive chemokine receptor blocker) throughout primary infection decreased CD4+and CD8+cell recruitment and increased viral replication. In RSV-infected, sensitized mice with eosinophilic disease, CCL5 production was further augmented; Met-RANTES treatment again reduced inflammatory cell recruitment and local cytokine production. A second wave of CCL5 production occurred on day 7, attributable to newly recruited T cells. Paradoxically, mice treated with Met-RANTES during primary infection demonstrated increased cellular infiltration during reinfection. We therefore show that RSV induces CCL5 production in the lung and this causes the recruitment of RSV-specific cells, including those making additional CCL5. If this action is blocked with Met-RANTES, inflammation decreases and viral clearance is delayed. However, the exact effects of chemokine modulation depend critically on time of administration, a factor that may potentially complicate the use of chemokine blockers in inflammatory diseases.
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Differential chemokine expression is observed in viral lung disease caused by respiratory syncytial virus.
“In addition to playing a distinct role in the early clinical course and persistence of SARS in infected patients, differential chemokine expression is observed in viral lung disease caused by respiratory syncytial virus (RSV) (36).”
From Into the Eye of the Cytokine Storm (2012) · cites this paper as [36]
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- Authors
- Culley, F. J., Pennycook, A. M. J., Tregoning, J. S., Dodd, J. S., Walzl, G., Wells, T. N., Hussell, T., & Openshaw, P. J. M.
- Affiliations
- Imperial College London (GB)
- Merck Serono S.A. (Switzerland) (CH)
- ORCID
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2006-08-15
- Volume
- 80
- Issue
- 16
- Pages
- 8151-8157
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- OpenAlex
- W2143412723
- Cited by
- 126
- References
- 40
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 8 · 2023: 4 · 2022: 10 · 2021: 11 · 2020: 12 · 2019: 6 · 2018: 8 · 2017: 4 · 2016: 4 · 2015: 2 · 2014: 8 · 2013: 3 · 2012: 9
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Virology (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Funders
- Wellcome Trust (055303/Z/98/Z, 54797/Z/98/Z, 071381)
- Topics
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Keywords
- CCL5/RANTES, respiratory syncytial virus, chemokine receptor blockade, eosinophilic inflammation, viral replication, T cell recruitment, CD4 and CD8 T cells
- MeSH terms
- Animals, Eosinophilia, Female, Mice, Inbred BALB C, Pneumonia, Viral, Respiratory Syncytial Viruses, RNA, Messenger, CD4-Positive T-Lymphocytes, Respiratory Syncytial Virus Infections, CD8-Positive T-Lymphocytes, Th2 Cells, Chemokine CCL5, Chemokines, CC, Mice
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