Shterzer Naama, Heyman Dariya, Shapiro Beny, Yaniv Abraham, Jackman Anna, Serour Francis, Chaouat Malka, Gonen Pinhas, Tommasino Massimo, Sherman Levana
Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Department of Pediatric Surgery, The E. Wolfson Medical Center, Holon, Israel.
Virology. 2014 Nov;468-470:647-659. doi: 10.1016/j.virol.2014.09.015. Epub 2014 Oct 14.
In the present study, E6E7 and E6 proteins of human papillomaviruses (HPVs) associated with skin warts and cancer were compared for their transforming and carcinogenic abilities in primary human keratinocytes (PHKs). We show that E6E7 of cancer associated beta HPV types, notably 49 and 24, were able to extend the life span and enhance the clonogenic efficiency of PHKs when maintained in serum free/low calcium medium. Activities of the beta HPV E6E7 were lower than those of HPV16 E6E7. In contrast, E6 proteins from HPV types detected in skin warts or cancer, notably 10, 49 and 38, attenuated UVB induced protective responses in PHKs including cell death, proliferation arrest and accumulation of the proapoptotic proteins, p53, bax or bak. Together, this investigation revealed functional differences and commonalities between HPVs associated with skin warts and cancer, and allowed the identification of specific properties of beta HPVs supporting their involvement in skin carcinogenesis.