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

• Main Authors: Cason John, Kell Barbara, Mant Christine A, Nath Rahul, Bible Jon M
• Format: Article
• Language: English
• Published: BMC 2006-08-01
• Series: Cancer Cell International
• Online Access: http://www.cancerci.com/content/6/1/19

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>We demonstrate that: (i) introduction of Thr⁶⁴into the reference E5 sequence of HPV-16 abrogates mitogenic activity: both were poorly transcribed in NIH-3T3 cells; (ii) substitution of Leu⁴⁴Val⁶⁵or, Thr³⁷Leu⁴⁴Val⁶⁵into 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 Tyr⁸into the Leu⁴⁴Val⁶⁵backbone inhibited E5 induced cell-growth and repression of p21 expression, despite high transcription levels.</p> <p>Conclusion</p> <p>The effects of HPV-16 E5 variants upon mitosis help to explain why Leu⁴⁴Val⁶⁵HPV-16 E5 variants are most prevalent in 'wild' pathogenic viral populations in the UK.</p>