Characterization of beta papillomavirus E4 expression in tumours from Epidermodysplasia Verruciformis patients and in experimental models.
This study provides a first characterisation of β-HPV life-cycle events in tumours abscised from EV patients (the human model of β-HPV-induced skin cancer), and shows how changes in E4 expression patterns relate to disease severity. β-HPV life-cycle has also been reconstructed in organotypic raft cultures created using EV-derived keratinocytes. In EV lesions and raft cultures, abundant cytoplasmic E4 expression was detectable in differentiating cells along with viral genome amplification as reported for other HPV types. E4 expression was also seen in PCNA-positive basal cells in some EV skin cancers as well as in tumours from HPV8CER (Complete Early Region) transgenic mice. In these lesions, E4 staining extended throughout the full thickness of the epithelium and was apparent in the markedly atypical cells. The loss of such staining at the tumour border suggests a distinct type of E4 dysregulation that may be exploited as a marker of viral expression during β-HPV-associated skin cancer progression.
Department of Clinical and Experimental Medicine, Medical School of Novara, Italy.
Cinzia
C
Borgogna
Elisa
E
Zavattaro
Marco
M
De Andrea
Heather M
HM
Griffin
Valentina
V
Dell'Oste
Barbara
B
Azzimonti
Manuela M
MM
Landini
Woei Ling
WL
Peh
Herbert
H
Pfister
John
J
Doorbar
Santo
S
Landolfo
Marisa
M
Gariglio
D000818:Animals; D052686:Betapapillomavirus / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004195:Disease Models, Animal; D004819:Epidermodysplasia Verruciformis / Q000821:virology*; D006801:Humans; D015603:Keratinocytes / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D030361:Papillomavirus Infections / Q000821:virology*
D009856:Oncogene Proteins, Viral