title: Human rhinovirus-induced inflammatory responses are inhibited by phosphatidylserine containing liposomes.
abstract: Human rhinovirus (HRV) infections are major contributors to the healthcare burden associated with acute exacerbations of chronic airway disease, such as chronic obstructive pulmonary disease and asthma. Cellular responses to HRV are mediated through pattern recognition receptors that may in part signal from membrane microdomains. We previously found Toll-like receptor signaling is reduced, by targeting membrane microdomains with a specific liposomal phosphatidylserine species, 1-stearoyl-2-arachidonoyl-sn-glycero-3-phospho-L-serine (SAPS). Here we explored the ability of this approach to target a clinically important pathogen. We determined the biochemical and biophysical properties and stability of SAPS liposomes and studied their ability to modulate rhinovirus-induced inflammation, measured by cytokine production, and rhinovirus replication in both immortalized and normal primary bronchial epithelial cells. SAPS liposomes rapidly partitioned throughout the plasma membrane and internal cellular membranes of epithelial cells. Uptake of liposomes did not cause cell death, but was associated with markedly reduced inflammatory responses to rhinovirus, at the expense of only modest non-significant increases in viral replication, and without impairment of interferon receptor signaling. Thus using liposomes of phosphatidylserine to target membrane microdomains is a feasible mechanism for modulating rhinovirus-induced signaling, and potentially a prototypic new therapy for viral-mediated inflammation.
authors.affiliation: Department of Infection, Immunity and Cardiovascular Disease, School of Medicine, Dentistry and Health, University of Sheffield, Sheffield, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Stokes
authors.affiliation: School of Life and Health Sciences, Aston University, Birmingham, Birmingham, UK.
authors.forename: R
authors.initials: R
authors.lastname: Kaur
authors.affiliation: Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: M R
authors.initials: MR
authors.lastname: Edwards
authors.affiliation: School of Medicine, Institute of Infection and Immunity, Cardiff University, Cardiff, UK.
authors.forename: M
authors.initials: M
authors.lastname: Mondhe
authors.affiliation: Faculty of Science, Department of Biomedical Sciences, University of Sheffield, Sheffield, UK.
authors.forename: D
authors.initials: D
authors.lastname: Robinson
authors.affiliation: Department of Infection, Immunity and Cardiovascular Disease, School of Medicine, Dentistry and Health, University of Sheffield, Sheffield, UK.
authors.forename: E C
authors.initials: EC
authors.lastname: Prestwich
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, UK.
authors.forename: R D
authors.initials: RD
authors.lastname: Hume
authors.affiliation: Department of Infection, Immunity and Cardiovascular Disease, School of Medicine, Dentistry and Health, University of Sheffield, Sheffield, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Marshall
authors.affiliation: School of Life and Health Sciences, Aston University, Birmingham, Birmingham, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Perrie
authors.affiliation: School of Medicine, Institute of Infection and Immunity, Cardiff University, Cardiff, UK.
authors.forename: V B
authors.initials: VB
authors.lastname: O'Donnell
authors.affiliation: School of Biosciences, Cardiff University, Cardiff, UK.
authors.forename: J L
authors.initials: JL
authors.lastname: Harwood
authors.affiliation: Department of Infection, Immunity and Cardiovascular Disease, School of Medicine, Dentistry and Health, University of Sheffield, Sheffield, UK.
authors.forename: I
authors.initials: I
authors.lastname: Sabroe
authors.affiliation: Department of Infection, Immunity and Cardiovascular Disease, School of Medicine, Dentistry and Health, University of Sheffield, Sheffield, UK.
authors.forename: L C
authors.initials: LC
authors.lastname: Parker
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D033942:Adaptor Proteins, Vesicular Transport / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D005786:Gene Expression Regulation / Q000187:drug effects; D054884:Host-Pathogen Interactions / Q000187:drug effects*; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D008081:Liposomes / Q000138:chemical synthesis / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000737:chemistry / Q000494:pharmacology*; D010742:Phospholipid Ethers / Q000737:chemistry / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D012229:Rhinovirus / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology; D015398:Signal Transduction; D014779:Virus Replication / Q000187:drug effects
chemical_list: C400184:1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; C483024:CCL5 protein, human; C114753:CXCL10 protein, human; C508606:CXCL8 protein, human; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D016209:Interleukin-8; D008081:Liposomes; C505371:MAVS protein, human; D010718:Phosphatidylserines; D010742:Phospholipid Ethers; C470409:TICAM1 protein, human; D016899:Interferon-beta