title: Expression pattern and subcellular localization of human papillomavirus minor capsid protein L2.
abstract: The expression pattern of human papillomavirus (HPV) capsid antigen L2 is poorly described, and the significance of its localization with both promyelocytic leukemia protein (PML) and Daxx in a subnuclear domain, nuclear domain 10 (ND-10), when ectopically expressed in tissue culture cells is controversial. To address whether ND-10 localization of L2 occurs in natural cervical lesions, we used a HPV16 and HPV18 L2-specific monoclonal antibody (RG-1), in addition to rabbit antiserum to HPV6 L2, to localize L2. Immunohistochemical staining with RG-1 produced diffuse staining in the nuclei of some cells located within the superficial epithelial layers in eight of nine cases of HPV16/18(+) cervical intraepithelial neoplasia grade 1 (CIN1); however, no staining was observed in HPV16/18(+) high-grade CIN (0 of 8 cases), normal cervical epithelium (0 of 20 cases), cervical squamous cell carcinoma (0 of 102 cases), adenocarcinoma (0 of 51 cases), or adenosquamous carcinoma (0 of 6 cases). HPV16/18(+) cervical lesions that express L2 exhibit higher HPV16/18 genome copies per cell compared with those that do not positively stain with RG-1 (P = 0.04). RG-1 staining of HeLa cells transfected with L2 expression constructs was frequently concentrated in the ND-10, particularly in cells expressing high levels of L2, and co-localized with the cellular markers of ND-10, PML, and Daxx. In contrast, L2 was primarily diffuse within the nucleus and distinct from ND-10 as defined by PML immunofluorescent staining in CIN lesions, condylomata, and HPV16-transduced organotypic cultures.
authors.affiliation: Department of Pathology, Johns Hopkins University Medical Institutions, Baltimore, Maryland, USA.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Lin
authors.forename: Anna V
authors.initials: AV
authors.lastname: Yemelyanova
authors.forename: Ratish
authors.initials: R
authors.lastname: Gambhira
authors.forename: Subhashini
authors.initials: S
authors.lastname: Jagu
authors.forename: Craig
authors.initials: C
authors.lastname: Meyers
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kirnbauer
authors.forename: Brigitte M
authors.initials: BM
authors.lastname: Ronnett
authors.forename: Patti E
authors.initials: PE
authors.lastname: Gravitt
authors.forename: Richard B S
authors.initials: RB
authors.lastname: Roden
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D036022:Capsid Proteins / Q000378:metabolism*; D056970:Co-Repressor Proteins; D005260:Female; D005455:Fluorescent Antibody Technique; D052816:Foreskin; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D009924:Organ Culture Techniques; D030361:Papillomavirus Infections / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D021381:Protein Transport; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D036022:Capsid Proteins; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; C063316:L2 protein, Human papillomavirus type 16; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human