This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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 Culp, T. D.
Right arrow Articles by Christensen, N. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Culp, T. D.
Right arrow Articles by Christensen, N. D.

 Previous Article  |  Next Article 

Journal of Virology, September 2006, p. 8940-8950, Vol. 80, No. 18
0022-538X/06/$08.00+0     doi:10.1128/JVI.00724-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Keratinocyte-Secreted Laminin 5 Can Function as a Transient Receptor for Human Papillomaviruses by Binding Virions and Transferring Them to Adjacent Cells{dagger}

Timothy D. Culp,1 Lynn R. Budgeon,1 M. Peter Marinkovich,3 Guerrino Meneguzzi,4 and Neil D. Christensen1,2*

The Jake Gittlen Cancer Research Foundation and Department of Pathology,1 Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033,2 Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305,3 INSERM U634, Faculté de Médecine, Université de Nice, F-06107 Nice Cedex, France4

Received 10 April 2006/ Accepted 27 June 2006

Human papillomaviruses (HPVs) replicate only in the terminally differentiating epithelium of the skin and mucosa. While infection of basal keratinocytes is considered a requirement for permissive infection, it remains unclear whether virions can specifically target basal cells for adsorption and uptake following epithelial wounding. We present evidence that HPV binds specifically to laminin 5 (LN5), a component of the extracellular matrix (ECM) secreted by migrating and basal keratinocytes. HPV type 11 capsids colocalized with LN5 in the ECM secreted by vaginal keratinocytes. Binding of both virions and virus-like particles to purified LN5 and to the LN5-rich ECM secreted by cultured keratinocytes was effectively blocked by pretreatment with anti-LN5 antibodies. HPV capsid binding to human cervical mucosa sections included the basement membrane which contains LN5. Cultured keratinocytes expressing {alpha}6 integrin, a transmembrane protein known to bind LN5, were readily infected by virions preadsorbed to LN5-containing substrates, whereas mutant keratinocytes lacking {alpha}6 integrin were relatively resistant to infection via this route. These findings suggest a model of natural HPV infection in which proliferating keratinocytes expressing {alpha}6 integrin at the site of epithelial wounding might be targeted by virions adsorbed transiently to LN5 secreted by migrating keratinocytes.

* Corresponding author. Mailing address: The Jake Gittlen Cancer Research Foundation, The Milton S. Hershey Medical Center, Pennsylvania State University, 500 University Drive, Hershey, PA 17033-2390. Phone: (717) 531-6185. Fax: (717) 531-5634. E-mail: ndc1{at}psu.edu.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, September 2006, p. 8940-8950, Vol. 80, No. 18
0022-538X/06/$08.00+0     doi:10.1128/JVI.00724-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Johnson, K. M., Kines, R. C., Roberts, J. N., Lowy, D. R., Schiller, J. T., Day, P. M. (2009). Role of Heparan Sulfate in Attachment to and Infection of the Murine Female Genital Tract by Human Papillomavirus. J. Virol. 83: 2067-2074 [Abstract] [Full Text]  
  • Lembo, D., Donalisio, M., Rusnati, M., Bugatti, A., Cornaglia, M., Cappello, P., Giovarelli, M., Oreste, P., Landolfo, S. (2008). Sulfated K5 Escherichia coli Polysaccharide Derivatives as Wide-Range Inhibitors of Genital Types of Human Papillomavirus. Antimicrob. Agents Chemother. 52: 1374-1381 [Abstract] [Full Text]  
  • Selinka, H.-C., Florin, L., Patel, H. D., Freitag, K., Schmidtke, M., Makarov, V. A., Sapp, M. (2007). Inhibition of Transfer to Secondary Receptors by Heparan Sulfate-Binding Drug or Antibody Induces Noninfectious Uptake of Human Papillomavirus. J. Virol. 81: 10970-10980 [Abstract] [Full Text]  
  • Knappe, M., Bodevin, S., Selinka, H.-C., Spillmann, D., Streeck, R. E., Chen, X. S., Lindahl, U., Sapp, M. (2007). Surface-exposed Amino Acid Residues of HPV16 L1 Protein Mediating Interaction with Cell Surface Heparan Sulfate. J. Biol. Chem. 282: 27913-27922 [Abstract] [Full Text]  
  • Smith, J. L., Campos, S. K., Ozbun, M. A. (2007). Human Papillomavirus Type 31 Uses a Caveolin 1- and Dynamin 2-Mediated Entry Pathway for Infection of Human Keratinocytes. J. Virol. 81: 9922-9931 [Abstract] [Full Text]  
  • Chiu, W.-L., Lin, C.-L., Yang, M.-H., Tzou, D.-L. M., Chang, W. (2007). Vaccinia Virus 4c (A26L) Protein on Intracellular Mature Virus Binds to the Extracellular Cellular Matrix Laminin. J. Virol. 81: 2149-2157 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»