This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tamanini, A.
Right arrow Articles by Cabrini, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tamanini, A.
Right arrow Articles by Cabrini, G.

 Previous Article  |  Next Article 

Journal of Virology, November 2006, p. 11241-11254, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.00721-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Interaction of Adenovirus Type 5 Fiber with the Coxsackievirus and Adenovirus Receptor Activates Inflammatory Response in Human Respiratory Cells{triangledown}

Anna Tamanini, Elena Nicolis, Alberto Bonizzato, Valentino Bezzerri, Paola Melotti, Baroukh M. Assael, and Giulio Cabrini*

Laboratory of Molecular Pathology, Cystic Fibrosis Center, University-Hospital of Verona, Piazzale Stefani 1, 37126 Verona, Italy

Received 10 April 2006/ Accepted 24 August 2006

The innate immune response to adenovirus (Ad)-derived gene transfer vectors has been shown to initiate immediately after interaction of Ad with respiratory epithelial cells, through the induction of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and JNK mitogen-activated protein kinase (MAPK), nuclear factor {kappa}B (NF-{kappa}B), and different proinflammatory genes. Ad serotypes 2 or 5 (Ad2/5) enter respiratory epithelia after initial binding of fiber with the coxsackievirus-adenovirus receptor (CAR) or, alternatively, with cell surface heparan sulfate glycosaminoglycans. Ad2/5 internalization is triggered by binding of penton base to cellular RGD-binding integrins. Here we investigated the role of the Ad5 surface domain proteins constituting the vector capsid, namely, the fiber, the penton base, and the hexon, on the transmembrane signals leading to the transcription of the different proinflammatory genes in the human respiratory A549 cell line. Interaction of Ad fiber with CAR activates both ERK1/2 and JNK MAPK and the nuclear translocation of NF-{kappa}B, whereas no activation was observed after exposing A549 cells to penton base and hexon proteins. Moreover, interaction of Ad fiber with CAR, but not heparan sulfate proteoglycans, promotes transcription of the chemokines interleukin-8, GRO-{alpha}, GRO-{gamma}, RANTES, and interferon-inducible protein 10. These results identify the binding of Ad5 fiber with the cellular CAR as a key proinflammatory activation event in epithelial respiratory cells that is independent of the transcription of Ad5 genes.

* Corresponding author. Mailing address: Laboratorio Patologia Molecolare, Centro Fibrosi Cistica, Azienda Ospedaliera-Universitaria, Piazzale Stefani 1, 37126 Verona, Italy. Phone: 39 045 807 2364. Fax: 39 045 807 2840. E-mail: giulio.cabrini{at}azosp.vr.it.

{triangledown} Published ahead of print on 6 September 2006.

Journal of Virology, November 2006, p. 11241-11254, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.00721-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Russell, W. C. (2009). Adenoviruses: update on structure and function. J. Gen. Virol. 90: 1-20 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»