Primary research

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

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

Department of Infectious Diseases, Second Floor New Guy's House, Guy's Hospital, Guy's, King's College and St Thomas' School of Medicine, King's College London, London SE19RT, UK

author email corresponding author email

Cancer Cell International 2006, 6:19doi:10.1186/1475-2867-6-19

Published:	9 August 2006

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.