Human Rhinovirus Infection Induces Airway Epithelial Cell Production of Human β-Defensin 2 Both In Vitro and In Vivo

• Published in: The Journal of immunology (1950) Vol. 172; no. 7; pp. 4637 - 4645
• Main Authors: Proud, David, Sanders, Scherer P, Wiehler, Shahina
• Format: Journal Article
• Language: English
• Published: United States 01.04.2004
• Subjects: Adult; beta-Defensins - biosynthesis; beta-Defensins - genetics; beta-Defensins - metabolism; Cell Line, Tumor; Common Cold - immunology; Common Cold - metabolism; Common Cold - virology; Female; Human rhinovirus; Humans; Interleukin-1 - physiology; Male; NF-kappa B - physiology; Promoter Regions, Genetic - immunology; Respiratory Mucosa - cytology; Respiratory Mucosa - immunology; Respiratory Mucosa - metabolism; Respiratory Mucosa - virology; Rhinovirus - classification; Rhinovirus - immunology; Rhinovirus - physiology; RNA, Messenger - biosynthesis; RNA, Messenger - metabolism; RNA, Viral - biosynthesis; Serotyping - classification; Time Factors; Virus Inactivation; Virus Replication - immunology
• DOI: 10.4049/jimmunol.172.7.4637
• ISSN: 0022-1767

We hypothesized that airway epithelial cells, the primary site of human rhinovirus (HRV) infection, provide a link between the innate and specific immune response to HRV via production of human β-defensin (HBD)-2, a potent in vitro attractant and activator of immature dendritic cells. Infection of primary cultures of human epithelial cells with several HRV serotypes induced expression of HBD-2 mRNA and protein, indicating that HBD-2 production was independent of viral receptor usage or mechanisms of viral RNA internalization. Induction of HBD-2 was dependent upon viral replication and could be mimicked by transfection of cells with synthetic dsRNA, but was not dependent upon epithelial production of IL-1. Studies with stable epithelial cell lines expressing HBD-2 promoter constructs, as well as inhibitor studies in primary cells, both demonstrated that induction of HBD-2 involves activation of the transcription factor, NF-κB. Other transcription factors must also be activated by HRV infection, however, as expression of HBD-3 mRNA was also induced and there is no putative NF-κB recognition sequence in the promoter of this gene. HBD-2 showed no direct antiviral activity against HRV. In vivo infection of normal human subjects with HRV-16 induced expression of mRNA for HBD-2 in nasal epithelial scrapings. Increases in mRNA correlated with viral titer and with increased levels of HBD-2 protein in nasal lavages. This represents the first demonstration that HRV infection induces epithelial expression of HBD-2 both in vitro and in vivo, and supports the concept that HBD-2 may play a role in host defense to HRV infection.