Human rhinovirus infection induces airway epithelial cell production of human beta-defensin 2 both in vitro and in vivo.
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 beta-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-kappaB. 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-kappaB 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.
Proud
David
D
Respiratory Research Group and Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada. dproud@ucalgary.ca
Sanders
Scherer P
SP
Wiehler
Shahina
S
D000328:Adult; D045744:Cell Line, Tumor; D003139:Common Cold / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D008297:Male; D016328:NF-kappa B / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D012367:RNA, Viral / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D012229:Rhinovirus / Q000145:classification / Q000276:immunology* / Q000502:physiology; D012703:Serotyping / Q000145:classification; D013997:Time Factors; D038301:Virus Inactivation; D014779:Virus Replication / Q000276:immunology; D023083:beta-Defensins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
C406407:DEFB1 protein, human; C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D007375:Interleukin-1; D016328:NF-kappa B; D012333:RNA, Messenger; D012367:RNA, Viral; D023083:beta-Defensins