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Journal of Virology, May 2008, p. 4638-4646, Vol. 82, No. 9
0022-538X/08/$08.00+0     doi:10.1128/JVI.00143-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Mechanisms of Human Papillomavirus Type 16 Neutralization by L2 Cross-Neutralizing and L1 Type-Specific Antibodies{triangledown}

Patricia M. Day,1* Ratish Gambhira,2 Richard B. S. Roden,2 Douglas R. Lowy,1 and John T. Schiller1

Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland,1 Department of Pathology, Johns Hopkins University, Baltimore, Maryland2

Received 18 January 2008/ Accepted 19 February 2008

Pseudovirions of human papillomavirus type 16 (HPV16), the principal etiologic agent in 50% of cervical cancers, were used as a model system to investigate the cell surface interactions involved in the exposure of the broadly cross-neutralizing papillomavirus L2 epitopes. These neutralizing epitopes were exposed only after cell surface binding and a subsequent change in capsid conformation that permitted cleavage by the cellular protease furin at a specific highly conserved site in L2 that is immediately upstream of the cross-neutralizing epitopes. Unexpectedly, binding of L2 antibodies led to the release of the capsid/antibody complexes from the cell surface and their accumulation on the extracellular matrix. Study of the dynamics of exposure of the L2 epitopes further revealed that representatives of the apparently dominant class of L1-specific neutralizing antibodies induced by virus-like particle vaccination prevent infection, not by preventing cell surface binding but rather by preventing the conformation change involved in exposure of the L2 neutralizing epitope. These findings suggest a dynamic model of virion-cell surface interactions that has implications for both evolution of viral serotypes and the efficacy of current and future HPV vaccines.

* Corresponding author. Mailing address: 37 Convent Drive, Room 4112, MSC 4263, National Institutes of Health, Bethesda, MD 20892. Phone: (301) 594-6945. Fax: (301) 480-5322. E-mail: pmd{at}nih.gov

{triangledown} Published ahead of print on 27 February 2008.

Journal of Virology, May 2008, p. 4638-4646, Vol. 82, No. 9
0022-538X/08/$08.00+0     doi:10.1128/JVI.00143-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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Copyright © 2008 by the American Society for Microbiology. All rights reserved.