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This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0902145v1 183/10/6151    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Fahey, L. M. Articles by Kast, W. M. PubMed PubMed Citation Articles by Fahey, L. M. Articles by Kast, W. M.

A Major Role for the Minor Capsid Protein of Human Papillomavirus Type 16 in Immune Escape¹

Laura M. Fahey,^2* Adam B. Raff,² Diane M. Da Silva, and W. Martin Kast^3*¶

^*Department of Molecular Microbiology and Immunology, Systems Biology and Disease Program, Department of Obstetrics and Gynecology and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033; and ^¶Cancer Research Center, University of Hawaii, Honolulu, HI 96822

High-risk human papillomavirus (HPV) infection of the cervical epithelium is causally linked with the generation of cervical cancer. HPV does not activate Langerhans cells (LC), the APC at the site of infection, leading to immune evasion. The HPV protein responsible for inducing this immune escape has not been determined. We demonstrate that LC exposed to the minor capsid protein L2 in HPV16L1L2 virus-like particles do not phenotypically or functionally mature. However, HPV16L1 virus-like particles significantly induce activation of LC. Our data suggest that the L2 protein plays a specific role in the induction of this immune escape of HPV16 through the manipulation of LC. This novel function is the first immune modulating action attributed to the L2 protein and adds significantly to our understanding of the mechanism of HPV immune escape.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was supported by National Institutes of Health Grant R01 CA 74397 and 1RC2 CA 148298 (to W.M.K.), National Institutes of Health Training Grant T32 AI07078 (to L.M.F.), and National Institutes of Health Training Grant T32 GM0607587 (to A.B.R.).

² L.M.F. and A.B.R. contributed equally to this study.

³ Address correspondence and reprint requests to Dr. W. Martin Kast, Norris Comprehensive Cancer Center, University of Southern California, 1450 Biggy Street, NRT 7507, Los Angeles, CA 90033. E-mail address: mkast{at}usc.edu

⁴ Abbreviations used in this paper: HPV, human papillomavirus; VLP, virus-like particle; LC, Langerhans cell; DC, dendritic cell; CFDA-SE, carboxyfluorescein diacetate, succinimidyl ester.