Viral interaction: a possible contributing factor in head and neck cancer progression.
CONCLUSIONS
Human herpesvirus-8 could potentiate the effects of human papillomavirus (HPV)-16 on cell cycle dysregulation by up-regulating the transcription of HPV-16 E7, which can lead to malignant transformation of normal epithelial cells.


OBJECTIVE
High-risk HPV-16 is known for its association with development of head and neck carcinoma, leading to considerable morbidity and mortality worldwide. HPV-16 produces two early proteins, E6 and E7, that can disrupt the cell cycle and transform cells. Other viruses may potentiate dysregulation of the cell cycle by HPV-16. Herpes viruses are known to produce replication transcription activators, which may contribute to the malignant transformation of normal cells. This study aimed to determine if the ORF50/Rta protein of HHV-8 binds to genomic regions within HPV-16 and alters the transcription and/or translation of E6 and E7 in HPV-infected cells.


METHODS
Protein shift assays determined the binding potential of ORF50 to various HPV-16 genomic regions. A real-time polymerase chain reaction (PCR) assay quantified the effect of ORF50 on the transcription of E6 and E7 within these cells. Finally, immunofluorescent confocal microscopy was used to quantify E6 and E7 protein levels within transfected cells and study their localization patterns.


RESULTS
The results reveal potential ORF50/Rta binding sites within HPV-16 and a significant up-regulation of E7 transcription in ORF50 transfected cells.
Underbrink
Michael P
MP
Departments of Otolaryngology, University of Texas Medical Branch, Galveston, TX 77555, USA. mpunderb@utmb.edu
Hoskins
Stephen L
SL
Pou
Anna M
AM
Albrecht
Thomas
T
D001665:Binding Sites; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D045744:Cell Line, Tumor; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D006258:Head and Neck Neoplasms / Q000821:virology*; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D012367:RNA, Viral / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic
C068651:E6 protein, Human papillomavirus type 16; D017874:Immediate-Early Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012367:RNA, Viral; D012097:Repressor Proteins; C417604:Rta protein, Human herpesvirus 8; D015534:Trans-Activators; C059731:oncogene protein E7, Human papillomavirus type 16