title: Analyses of variant human papillomavirus type-16 E5 proteins for their ability to induce mitogenesis of murine fibroblasts.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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. rahul.nath@gstt.nhs.uk
authors.forename: Rahul
authors.initials: R
authors.lastname: Nath
authors.forename: Christine A
authors.initials: CA
authors.lastname: Mant
authors.forename: Barbara
authors.initials: B
authors.lastname: Kell
authors.forename: John
authors.initials: J
authors.lastname: Cason
authors.forename: Jon M
authors.initials: JM
authors.lastname: Bible