Abstract
Vaccination with formalin-inactivated respiratory syncytial virus (FI-RSV) vaccine or RSV G glycoprotein results in enhanced pulmonary disease after live RSV infection. Enhanced pulmonary disease is characterized by pulmonary eosinophilia and is associated with a substantial inflammatory response. We show that the absence of the G glycoprotein or G glycoprotein CX3C motif during FI-RSV vaccination or RSV challenge of FI-RSV-vaccinated mice, or treatment with anti-substance P or anti-CX3CR1 antibodies, reduces or eliminates enhanced pulmonary disease, modifies T-cell receptor Vbeta usage, and alters CC and CXC chemokine expression. These data suggest that the G glycoprotein, and in particular the G glycoprotein CX3C motif, is key in the enhanced inflammatory response to FI-RSV vaccination, possibly through the induction of substance P.
MeSH terms
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Amino Acid Motifs
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Animals
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CD4-Positive T-Lymphocytes / immunology
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CX3C Chemokine Receptor 1
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Cell Movement
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Chemokines / genetics
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Chemokines, CX3C / metabolism*
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Female
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Formaldehyde
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Membrane Proteins*
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Mice
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Mice, Inbred BALB C
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Pulmonary Eosinophilia / etiology*
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RNA, Messenger / analysis
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Receptors, Antigen, T-Cell, alpha-beta / physiology
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Receptors, Chemokine / metabolism*
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Respiratory Syncytial Viruses / immunology*
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Substance P / biosynthesis*
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Vaccination / adverse effects
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Vaccines, Inactivated / toxicity
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Viral Proteins / chemistry
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Viral Proteins / physiology*
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Viral Vaccines / toxicity*
Substances
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CX3C Chemokine Receptor 1
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CX3CR1 protein, human
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Chemokines
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Chemokines, CX3C
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Membrane Proteins
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RNA, Messenger
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Chemokine
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Vaccines, Inactivated
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Viral Proteins
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Viral Vaccines
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Formaldehyde
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Substance P