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Cancer Cell International
Published in: Cancer Cell International 1/2006

Open Access 01-12-2006 | Primary research

Analyses of variant human papillomavirus type-16 E5 proteins for their ability to induce mitogenesis of murine fibroblasts

Authors: Rahul Nath, Christine A Mant, Barbara Kell, John Cason, Jon M Bible

Published in: Cancer Cell International | Issue 1/2006

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Abstract

Background

Human papillomavirus type 16 (HPV-16) E5 protein co-operates with epidermal growth factor to stimulate mitogenesis of murine fibroblasts. Currently, little is known about which viral amino acids are involved in this process. Using sequence variants of HPV-16 E5 we have investigated their effects upon E5 transcription, cell-cycling and cell-growth of murine fibroblasts.

Results

We demonstrate that: (i) introduction of Thr64 into the reference E5 sequence of HPV-16 abrogates mitogenic activity: both were poorly transcribed in NIH-3T3 cells; (ii) substitution of Leu44Val65 or, Thr37Leu44Val65 into the HPV-16 E5 reference backbone resulted in high transcription in NIH-3T3 cells, enhanced cell-cycle progression and high cell-growth; and, (iii) inclusion of Tyr8 into the Leu44Val65 backbone inhibited E5 induced cell-growth and repression of p21 expression, despite high transcription levels.

Conclusion

The effects of HPV-16 E5 variants upon mitosis help to explain why Leu44Val65 HPV-16 E5 variants are most prevalent in 'wild' pathogenic viral populations in the UK.
Appendix
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Metadata
Title
Analyses of variant human papillomavirus type-16 E5 proteins for their ability to induce mitogenesis of murine fibroblasts
Authors
Rahul Nath
Christine A Mant
Barbara Kell
John Cason
Jon M Bible
Publication date
01-12-2006
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2006
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-6-19

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