Cited by 126Chemokine receptors and signalingRespiratory viral infections researchAsthma and respiratory diseases

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Role of CCL5 (RANTES) in Viral Lung Disease

Culley, Fiona J., Pennycook, Alasdair M. J., Tregoning, John S., Dodd, Jonathan S., Walzl, Gerhard, Wells, Timothy N., Hussell, Tracy, Openshaw, Peter J. M.·2006·Journal of Virology

DOI 10.1128/jvi.00496-06

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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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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: Culley, Fiona J.
Tregoning, John S.
Walzl, Gerhard
Wells, Timothy N.
Hussell, Tracy
Openshaw, Peter J. M.
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
DOI: 10.1128/jvi.00496-06
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
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
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 › Pulmonary and Respiratory Medicine › 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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Role of CCL5 (RANTES) in Viral Lung Disease

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