E4 antibodies facilitate detection and type-assignment of active HPV infection in cervical disease

Autor: Rebecca Marnane, Anco Molijn, Wim Quint, Vincent Dewar, Zhonglin Wu, Christine Van Hoof, John Doorbar, Frank Struyf, David G. Jenkins, Heather Griffin, Brigitte Desiree Alberte Colau
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Pathology
Viral Diseases
Biopsy
Uterine Cervical Neoplasms
Alphapapillomavirus
Mice
Cervical cancer
Mice
Inbred BALB C
Multidisciplinary
biology
medicine.diagnostic_test
HPV infection
Antibodies
Monoclonal
Obstetrics and Gynecology
virus diseases
Immunohistochemistry
Koilocyte
female genital diseases and pregnancy complications
Infectious Diseases
Biomarker (medicine)
Medicine
Female
Rabbits
Antibody
Immunohistochemical Analysis
Research Article
medicine.medical_specialty
Human Papillomavirus Infection
medicine.drug_class
Science
Blotting
Western
Molecular Sequence Data
Sexually Transmitted Diseases
Enzyme-Linked Immunosorbent Assay
Monoclonal antibody
Microbiology
Diagnostic Medicine
Virology
medicine
Animals
Humans
Amino Acid Sequence
Biology
Sequence Homology
Amino Acid
Genitourinary Infections
Papillomavirus Infections
medicine.disease
Viral Disease Diagnosis
Viruses and Cancer
DNA
Viral
biology.protein
Immunologic Techniques
Clinical Immunology
Zdroj: PLoS ONE, Vol 7, Iss 12, p e49974 (2012)
PLoS ONE
ISSN: 1932-6203
Popis: High-risk human papillomavirus (HPV) infections are the cause of nearly all cases of cervical cancer. Although the detection of HPV DNA has proved useful in cervical diagnosis, it does not necessarily predict disease presence or severity, and cannot conclusively identify the causative type when multiple HPVs are present. Such limitations may be addressed using complementary approaches such as cytology, laser capture microscopy, and/or the use of infection biomarkers. One such infection biomarker is the HPV E4 protein, which is expressed at high level in cells that are supporting (or have supported) viral genome amplification. Its distribution in lesions has suggested a role in disease staging. Here we have examined whether type-specific E4 antibodies may also allow the identification and/or confirmation of causal HPV-type. To do this, type-specific polyclonal and monoclonal antibodies against three E4 proteins (HPV-16, -18, and -58) were generated and validated by ELISA and western blotting, and by immunohistochemistry (IHC) staining of epithelial rafts containing these individual HPV types. Type-specific detection of HPV and its associated disease was subsequently examined using formalin-fixed paraffin-embedded cervical intra-epithelial neoplasias (CIN, (n = 247)) and normal controls (n = 28). All koilocytotic CIN1 lesions showed type-specific E4 expression of their respective HPV types. Differences were noted amongst E4 expression patterns in CIN3. HPV-18 E4 was not detected in any of the 6 HPV-18 DNA-positive CIN3 lesions examined, whereas in HPV-16 and -58 CIN3, 28/37 (76%) and 5/9 (55.6%) expressed E4 respectively, usually in regions of epithelial differentiation. Our results demonstrate that type-specific E4 antibodies can be used to help establish causality, as may be required when multiple HPV types are detected. The unique characteristics of the E4 biomarker suggest a role in diagnosis and patient management particularly when used in combination.
Databáze: OpenAIRE
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