Modulation of protease activated receptor 1 influences human metapneumovirus disease severity in a mouse model.
Human metapneumovirus (hMPV) infection causes acute respiratory tract infections (RTI) which can result in hospitalization of both children and adults. To date, no antiviral or vaccine is available for this common viral infection. Immunomodulators could represent an interesting strategy for the trea...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3755973?pdf=render |
| _version_ | 1817994809720176640 |
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| author | Laetitia Aerts Marie-Ève Hamelin Chantal Rhéaume Sophie Lavigne Christian Couture Woojin Kim Delia Susan-Resiga Annik Prat Nabil G Seidah Nathalie Vergnolle Beatrice Riteau Guy Boivin |
| author_facet | Laetitia Aerts Marie-Ève Hamelin Chantal Rhéaume Sophie Lavigne Christian Couture Woojin Kim Delia Susan-Resiga Annik Prat Nabil G Seidah Nathalie Vergnolle Beatrice Riteau Guy Boivin |
| author_sort | Laetitia Aerts |
| collection | DOAJ |
| description | Human metapneumovirus (hMPV) infection causes acute respiratory tract infections (RTI) which can result in hospitalization of both children and adults. To date, no antiviral or vaccine is available for this common viral infection. Immunomodulators could represent an interesting strategy for the treatment of severe viral infection. Recently, the role of protease-activated receptors (PAR) in inflammation, coagulation and infection processes has been of growing interest. Herein, the effects of a PAR1 agonist and a PAR1 antagonist on hMPV infection were investigated in BALB/c mice. Intranasal administration of the PAR1 agonist resulted in increased weight loss and mortality of infected mice. Conversely, the PAR1 antagonist was beneficial to hMPV infection by decreasing weight loss and clinical signs and by significantly reducing pulmonary inflammation, pro-inflammatory cytokine levels (including IL-6, KC and MCP-1) and recruitment of immune cells to the lungs. In addition, a significant reduction in pulmonary viral titers was also observed in the lungs of PAR1 antagonist-treated mice. Despite no apparent direct effect on virus replication during in vitro experiments, an important role for PAR1 in the regulation of furin expression in the lungs was shown for the first time. Further experiments indicated that the hMPV fusion protein can be cleaved by furin thus suggesting that PAR1 could have an effect on viral infectivity in addition to its immunomodulatory properties. Thus, inhibition of PAR1 by selected antagonists could represent an interesting strategy for decreasing the severity of paramyxovirus infections. |
| first_indexed | 2024-04-14T01:57:05Z |
| format | Article |
| id | doaj.art-60c082ebebb94dff857b6f7940f1ce5e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T01:57:05Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-60c082ebebb94dff857b6f7940f1ce5e2022-12-22T02:18:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7252910.1371/journal.pone.0072529Modulation of protease activated receptor 1 influences human metapneumovirus disease severity in a mouse model.Laetitia AertsMarie-Ève HamelinChantal RhéaumeSophie LavigneChristian CoutureWoojin KimDelia Susan-ResigaAnnik PratNabil G SeidahNathalie VergnolleBeatrice RiteauGuy BoivinHuman metapneumovirus (hMPV) infection causes acute respiratory tract infections (RTI) which can result in hospitalization of both children and adults. To date, no antiviral or vaccine is available for this common viral infection. Immunomodulators could represent an interesting strategy for the treatment of severe viral infection. Recently, the role of protease-activated receptors (PAR) in inflammation, coagulation and infection processes has been of growing interest. Herein, the effects of a PAR1 agonist and a PAR1 antagonist on hMPV infection were investigated in BALB/c mice. Intranasal administration of the PAR1 agonist resulted in increased weight loss and mortality of infected mice. Conversely, the PAR1 antagonist was beneficial to hMPV infection by decreasing weight loss and clinical signs and by significantly reducing pulmonary inflammation, pro-inflammatory cytokine levels (including IL-6, KC and MCP-1) and recruitment of immune cells to the lungs. In addition, a significant reduction in pulmonary viral titers was also observed in the lungs of PAR1 antagonist-treated mice. Despite no apparent direct effect on virus replication during in vitro experiments, an important role for PAR1 in the regulation of furin expression in the lungs was shown for the first time. Further experiments indicated that the hMPV fusion protein can be cleaved by furin thus suggesting that PAR1 could have an effect on viral infectivity in addition to its immunomodulatory properties. Thus, inhibition of PAR1 by selected antagonists could represent an interesting strategy for decreasing the severity of paramyxovirus infections.http://europepmc.org/articles/PMC3755973?pdf=render |
| spellingShingle | Laetitia Aerts Marie-Ève Hamelin Chantal Rhéaume Sophie Lavigne Christian Couture Woojin Kim Delia Susan-Resiga Annik Prat Nabil G Seidah Nathalie Vergnolle Beatrice Riteau Guy Boivin Modulation of protease activated receptor 1 influences human metapneumovirus disease severity in a mouse model. PLoS ONE |
| title | Modulation of protease activated receptor 1 influences human metapneumovirus disease severity in a mouse model. |
| title_full | Modulation of protease activated receptor 1 influences human metapneumovirus disease severity in a mouse model. |
| title_fullStr | Modulation of protease activated receptor 1 influences human metapneumovirus disease severity in a mouse model. |
| title_full_unstemmed | Modulation of protease activated receptor 1 influences human metapneumovirus disease severity in a mouse model. |
| title_short | Modulation of protease activated receptor 1 influences human metapneumovirus disease severity in a mouse model. |
| title_sort | modulation of protease activated receptor 1 influences human metapneumovirus disease severity in a mouse model |
| url | http://europepmc.org/articles/PMC3755973?pdf=render |
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