Myristoylated rhinovirus VP4 protein activates TLR2-dependent pro-inflammatory gene expression.
dc.contributor.author | Bentley, JK | |
dc.contributor.author | Han, M | |
dc.contributor.author | Jaipalli, S | |
dc.contributor.author | Hinde, J | |
dc.contributor.author | Lei, J | |
dc.contributor.author | Ishikawa, T | |
dc.contributor.author | Goldsmith, AM | |
dc.contributor.author | Rajput, C | |
dc.contributor.author | Hershenson, MB | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2023-02-01T17:52:30Z | |
dc.date.available | 2023-02-01T17:52:30Z | |
dc.date.issued | 2019-07-01 | |
dc.identifier.issn | 1040-0605 | |
dc.identifier.issn | 1522-1504 | |
dc.identifier.uri | https://www.ncbi.nlm.nih.gov/pubmed/30908938 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/175727 | en |
dc.description.abstract | Asthma exacerbations are often caused by rhinovirus (RV). We and others have shown that Toll-like receptor 2 (TLR2), a membrane surface receptor that recognizes bacterial lipopeptides and lipoteichoic acid, is required and sufficient for RV-induced proinflammatory responses in vitro and in vivo. We hypothesized that viral protein-4 (VP4), an internal capsid protein that is myristoylated upon viral replication and externalized upon viral binding, is a ligand for TLR2. Recombinant VP4 and myristoylated VP4 (MyrVP4) were purified by Ni-affinity chromatography. MyrVP4 was also purified from RV-A1B-infected HeLa cells by urea solubilization and anti-VP4 affinity chromatography. Finally, synthetic MyrVP4 was produced by chemical peptide synthesis. MyrVP4-TLR2 interactions were assessed by confocal fluorescence microscopy, fluorescence resonance energy transfer (FRET), and monitoring VP4-induced cytokine mRNA expression in the presence of anti-TLR2 and anti-VP4. MyrVP4 and TLR2 colocalized in TLR2-expressing HEK-293 cells, mouse bone marrow-derived macrophages, human bronchoalveolar macrophages, and human airway epithelial cells. Colocalization was absent in TLR2-null HEK-293 cells and blocked by anti-TLR2 and anti-VP4. Cy3-labeled MyrVP4 and Cy5-labeled anti-TLR2 showed an average fractional FRET efficiency of 0.24 ± 0.05, and Cy5-labeled anti-TLR2 increased and unlabeled MyrVP4 decreased FRET efficiency. MyrVP4-induced chemokine mRNA expression was higher than that elicited by VP4 alone and was attenuated by anti-TLR2 and anti-VP4. Cytokine expression was similarly increased by MyrVP4 purified from RV-infected HeLa cells and synthetic MyrVP4. We conclude that, during RV infection, MyrVP4 and TLR2 interact to generate a proinflammatory response. | |
dc.format.medium | Print-Electronic | |
dc.language | eng | |
dc.publisher | American Physiological Society | |
dc.subject | Toll-like receptor | |
dc.subject | asthma | |
dc.subject | cytokine | |
dc.subject | macrophage | |
dc.subject | rhinovirus | |
dc.subject | Adolescent | |
dc.subject | Amino Acid Sequence | |
dc.subject | Animals | |
dc.subject | Asthma | |
dc.subject | Capsid Proteins | |
dc.subject | Child | |
dc.subject | Eosinophilia | |
dc.subject | Epithelial Cells | |
dc.subject | Female | |
dc.subject | HEK293 Cells | |
dc.subject | HeLa Cells | |
dc.subject | Host-Pathogen Interactions | |
dc.subject | Humans | |
dc.subject | Macrophages | |
dc.subject | Male | |
dc.subject | Mice | |
dc.subject | Mice, Inbred C57BL | |
dc.subject | Myristic Acids | |
dc.subject | Picornaviridae Infections | |
dc.subject | Protein Binding | |
dc.subject | Protein Processing, Post-Translational | |
dc.subject | Rhinovirus | |
dc.subject | Signal Transduction | |
dc.subject | Toll-Like Receptor 2 | |
dc.subject | Viral Proteins | |
dc.subject | Virus Replication | |
dc.title | Myristoylated rhinovirus VP4 protein activates TLR2-dependent pro-inflammatory gene expression. | |
dc.type | Article | |
dc.identifier.pmid | 30908938 | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/175727/2/ajplung.00365.2018.pdf | |
dc.identifier.doi | 10.1152/ajplung.00365.2018 | |
dc.identifier.doi | https://dx.doi.org/10.7302/6941 | |
dc.identifier.source | Am J Physiol Lung Cell Mol Physiol. | |
dc.description.version | Published version | |
dc.date.updated | 2023-02-01T17:52:28Z | |
dc.identifier.orcid | 0000-0001-8865-7979 | |
dc.identifier.volume | 317 | |
dc.identifier.issue | 1 | |
dc.identifier.startpage | L57 | |
dc.identifier.endpage | L70 | |
dc.identifier.name-orcid | Bentley, JK; 0000-0001-8865-7979 | |
dc.identifier.name-orcid | Han, M | |
dc.identifier.name-orcid | Jaipalli, S | |
dc.identifier.name-orcid | Hinde, J | |
dc.identifier.name-orcid | Lei, J | |
dc.identifier.name-orcid | Ishikawa, T | |
dc.identifier.name-orcid | Goldsmith, AM | |
dc.identifier.name-orcid | Rajput, C | |
dc.identifier.name-orcid | Hershenson, MB | |
dc.working.doi | 10.7302/6941 | en |
dc.owningcollname | Pediatrics and Communicable Diseases, Department of |
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