Transformation of Primary BRK Cells by Human Papillomavirus Type 16 and EJ-ras is Increased by Overexpression of the Viral E2 Protein

The human papillomavirus type 16 (HPV-16) status of 43 cervical biopsies, which had been characterized histologically as normal, various grades of cervical intraepithelial neoplasia (CIN) and invasive squamous cell carcinoma, was examined by using (i) a novel antibody against the HPV-16 E2 protein, (ii) sensitive HPV-16 DNA in situ hybridization and (iii) microdissection/PCR for the E2 ORF. The data indicate that E2 protein expression is highest in koilocytes in lower-grade CIN (I), but decreases with increasing grade, whereas the detection of HPV DNA is delayed until CIN I/II, rising to the highest levels in carcinoma cells. Co-localization of E2 with HPV-16 DNA-positive cells was most commonly observed in koilocytes in CIN II lesions. PCR analyses of microdissected epithelium from the same or serial sections indicated that E2 ORFs were retained in an intact form in a number of higher-grade CIN lesions and invasive carcinomas.

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Search for cellular partners of human papillomavirus type 16 E2 protein

Archives of Virology ◽

10.1007/s00705-008-0061-6 ◽

2008 ◽

Vol 153 (5) ◽

pp. 983-990 ◽

Cited By ~ 7

Author(s):

Agnieszka K. Olejnik-Schmidt ◽

Marcin T. Schmidt ◽

Witold Kędzia ◽

Anna Goździcka-Józefiak

Keyword(s):

Human Papillomavirus ◽

E2 Protein ◽

Human Papillomavirus Type 16

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Interaction of Daxx and human papillomavirus type 16 E2 protein

Molecular Biology ◽

10.1134/s0026893314040165 ◽

2014 ◽

Vol 48 (4) ◽

pp. 594-598 ◽

Cited By ~ 1

Author(s):

S. Y. Tang ◽

L. Li ◽

Y. Liu ◽

A. Y. Liu ◽

M. J. Yu ◽

...

Keyword(s):

Human Papillomavirus ◽

E2 Protein ◽

Human Papillomavirus Type 16

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Transcription-modulatory activities of differentially spliced cDNAs encoding the E2 protein of human papillomavirus type 16

Journal of General Virology ◽

10.1099/0022-1317-80-9-2461 ◽

1999 ◽

Vol 80 (9) ◽

pp. 2461-2470 ◽

Cited By ~ 11

Author(s):

Nathalie Alloul ◽

Levana Sherman

Keyword(s):

Human Papillomavirus ◽

Regulatory Protein ◽

Protein Translation ◽

Long Control Region ◽

Dependent Manner ◽

E2 Protein ◽

Reading Frame ◽

Human Papillomavirus Type 16 ◽

C33a Cell ◽

Alternatively Spliced

Human papillomavirus (HPV) type 16 expresses a variety of alternatively spliced polycistronic mRNAs encoding the E2 transcription-regulatory protein. These mRNAs initiate at the p97 promoter and contain the 880/2708 (a-type), 880/2581 (a′-type) and 226/2708 (d-type) splice sites upstream from the E2 open reading frame (ORF). Recent studies investigating the translational capacities of partial cDNAs representing three of these mRNAs indicated their abilities to function in E2 protein translation, although at different efficiencies. In the present study, the transcription-regulatory activities of the E2 cDNAs towards the virus long control region (LCR) have been examined. LCR regulation was evaluated in transient transfection assays by using the chloramphenicol acetyltransferase reporter gene linked to the HPV-16 LCR. Transfections were carried out into fibroblast (Cf2Th) and epithelial (C33A) cell lines. It is shown that all three E2 cDNAs transrepressed the virus LCR in a dose-dependent manner. Transrepression was mainly dependent on the function of the E2 ORF and was abolished or markedly reduced by premature termination or truncation of the E2 ORF. Transrepression activities exhibited by the various E2 cDNAs correlated with the previously defined efficiencies of E2 protein translation from the respective templates. The truncated E2 cDNAs exhibited variable low regulatory activities that correlated with the activities of the 5′ ORFs contained in each cDNA. The E6I and E1C ORFs transactivated the virus LCR whereas the E6IV cDNA transrepressed LCR activity. Thus, the 5′ ORFs contribute in different manners to the overall activities of the polycistronic cDNAs.

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