Expression pattern and subcellular localization of human papillomavirus minor capsid protein L2

Zhenhua Lin, Anna V. Yemelyanova, Ratish Gambhira, Subhashini Jagu, Craig Meyers, Reinhard Kirnbauer, Brigitte Maria Ronnett, Patti E. Gravitt, Richard S Roden

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)136-143
Number of pages8
JournalAmerican Journal of Pathology
Volume174
Issue number1
DOIs
StatePublished - Jan 2009

Fingerprint

Capsid Proteins
Staining and Labeling
Adenosquamous Carcinoma
Cervical Intraepithelial Neoplasia
Capsid
Cell Nucleus
HeLa Cells
Immune Sera
Squamous Cell Carcinoma
Adenocarcinoma
Coloring Agents
Epithelium
Cell Culture Techniques
Monoclonal Antibodies
Genome
Rabbits
Antigens
Promyelocytic Leukemia Protein

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Expression pattern and subcellular localization of human papillomavirus minor capsid protein L2. / Lin, Zhenhua; Yemelyanova, Anna V.; Gambhira, Ratish; Jagu, Subhashini; Meyers, Craig; Kirnbauer, Reinhard; Ronnett, Brigitte Maria; Gravitt, Patti E.; Roden, Richard S.

In: American Journal of Pathology, Vol. 174, No. 1, 01.2009, p. 136-143.

Research output: Contribution to journalArticle

Lin, Zhenhua ; Yemelyanova, Anna V. ; Gambhira, Ratish ; Jagu, Subhashini ; Meyers, Craig ; Kirnbauer, Reinhard ; Ronnett, Brigitte Maria ; Gravitt, Patti E. ; Roden, Richard S. / Expression pattern and subcellular localization of human papillomavirus minor capsid protein L2. In: American Journal of Pathology. 2009 ; Vol. 174, No. 1. pp. 136-143.
@article{04218be089d949c2ad2c14b26986a416,
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.",
author = "Zhenhua Lin and Yemelyanova, {Anna V.} and Ratish Gambhira and Subhashini Jagu and Craig Meyers and Reinhard Kirnbauer and Ronnett, {Brigitte Maria} and Gravitt, {Patti E.} and Roden, {Richard S}",
year = "2009",
month = "1",
doi = "10.2353/ajpath.2009.080588",
language = "English (US)",
volume = "174",
pages = "136--143",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Expression pattern and subcellular localization of human papillomavirus minor capsid protein L2

AU - Lin, Zhenhua

AU - Yemelyanova, Anna V.

AU - Gambhira, Ratish

AU - Jagu, Subhashini

AU - Meyers, Craig

AU - Kirnbauer, Reinhard

AU - Ronnett, Brigitte Maria

AU - Gravitt, Patti E.

AU - Roden, Richard S

PY - 2009/1

Y1 - 2009/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=58249119452&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58249119452&partnerID=8YFLogxK

U2 - 10.2353/ajpath.2009.080588

DO - 10.2353/ajpath.2009.080588

M3 - Article

C2 - 19095951

AN - SCOPUS:58249119452

VL - 174

SP - 136

EP - 143

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 1

ER -