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
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 Google Scholar
Google Scholar
Right arrow Articles by Johnson, K. M.
Right arrow Articles by Day, P. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Johnson, K. M.
Right arrow Articles by Day, P. M.

 Previous Article  |  Next Article 

Journal of Virology, March 2009, p. 2067-2074, Vol. 83, No. 5
0022-538X/09/$08.00+0     doi:10.1128/JVI.02190-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Role of Heparan Sulfate in Attachment to and Infection of the Murine Female Genital Tract by Human Papillomavirus{triangledown}

Katherine M. Johnson, Rhonda C. Kines, Jeffrey N. Roberts, Douglas R. Lowy, John T. Schiller, and Patricia M. Day*

Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Received 16 October 2008/ Accepted 4 December 2008

The host factors required for in vivo infection have not been investigated for any papillomavirus. Using a recently developed murine cervicovaginal challenge model, we evaluated the importance of heparan sulfate proteoglycans (HSPGs) in human papillomavirus (HPV) infection of the murine female genital tract. We examined HPV type 16 (HPV16) as well as HPV31 and HPV5, for which some evidence suggests that they may differ from HPV16 in their utilization of HSPGs as their primary attachment factor in vitro. Luciferase-expressing pseudovirus of all three types infected the mouse genital tract, although HPV5, which normally infects nongenital epidermis, was less efficient. Heparinase III treatment of the genital tract significantly inhibited infection of all three types by greater than 90% and clearly inhibited virion attachment to the basement membrane and cell surfaces, establishing that HSPGs are the primary attachment factors for these three viruses in vivo. However, the pseudoviruses differed in their responses to treatment with various forms of heparin, a soluble analog of heparan sulfate. HPV16 and HPV31 infections were effectively inhibited by a highly sulfated form of heparin, but HPV5 was not, although it bound the compound. In contrast, a N-desulfated and N-acylated variant preferentially inhibited HPV5. Inhibition of infection paralleled the relative ability of the variants to inhibit basement membrane and cell surface binding. We speculate that cutaneous HPVs, such as HPV5, and genital mucosal HPVs, such as HPV16 and -31, may have evolved to recognize different forms of HSPGs to enable them to preferentially infect keratinocytes at different anatomical sites.

* 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 10 December 2008.

Journal of Virology, March 2009, p. 2067-2074, Vol. 83, No. 5
0022-538X/09/$08.00+0     doi:10.1128/JVI.02190-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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