Vascular endothelial growth factor induction by rhinovirus infection

• Published in: Journal of medical virology 2006-05, Vol.78 (5), p.666-672
• Main Authors: De Silva, Dinesha, Dagher, Hayat, Ghildyal, Reena, Lindsay, Mandy, Li, Xun, Freezer, Nicholas J., Wilson, John W., Bardin, Philip G.
• Format: Article
• Language: English
• Subjects: Asthma - complications; Asthma - metabolism; Biological and medical sciences; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Epithelial Cells - metabolism; Epithelial Cells - virology; epithelium; fibroblast; Fibroblasts - metabolism; Fibroblasts - virology; Fundamental and applied biological sciences. Psychology; Human viral diseases; Humans; Infectious diseases; isoform; Medical sciences; Microbiology; Miscellaneous; nasal aspirates; Nasal Mucosa - metabolism; Picornaviridae Infections - complications; Picornaviridae Infections - metabolism; Picornaviridae Infections - virology; Polymerase Chain Reaction; Respiratory syncytial virus; Rhinovirus; Rhinovirus - physiology; RNA, Messenger - genetics; Species Specificity; Vascular Endothelial Growth Factor A - analysis; Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - genetics; VEGF; Viral diseases; Virology
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.20591

Vascular participation manifested by a runny nose (rhinorrhea) is a prominent feature of the acute consequences of rhinovirus infection. Vascular endothelial growth factor (VEGF) is an angiogenic factor that also induces potent increases in vascular permeability; it is a candidate mediator of rhinorrhea in response to rhinovirus infection as well as contributing to enhanced vascular leakage in rhinovirus‐linked asthma exacerbations. It has been shown that rhinovirus induces significant increases in both VEGF protein and mRNA in primary airway fibroblasts [Ghildyal et al. (2005): J Med Virol 75:608–615]. The current studies assessed VEGF responses to rhinovirus in primary culture airway epithelium, in epithelial and fibroblast cell lines and in rhinovirus‐infected nasal secretions. Epithelial and fibroblast cells were infected with rhinovirus serotype 16 and VEGF protein and isoforms assessed by ELISA and RT‐PCR, respectively. VEGF protein was released by both epithelial and fibroblast cell lines and primary airway epithelial cells in culture but was not increased following rhinovirus infection. PCR products coding for four or five of the six known VEGF isoforms were produced (121, 145, 165 and 183, and/or 189 amino acids) in cell lines and primary culture cells, but no specific isoform was linked to rhinovirus infection. Nasal VEGF was also measured in a cohort of asthmatics with verified rhinovirus and respiratory syncytial virus (RSV) infection. VEGF was not raised following rhinovirus infection alone, but was increased significantly if concomitant RSV infection was present. The data suggest that fibroblasts rather than the epithelium may play a key role in VEGF mediated vascular responses after rhinovirus infection. This may aid recruitment of inflammatory cells and contribute to airway inflammation and bronchial obstruction. J. Med. Virol. 78:666–672, 2006. © 2006 Wiley‐Liss, Inc.