Lecture by Director-General of the ICGEB Lawrence Banks «Human Papillomaviruses: From Infectious Entry to Malignancy»

Lawrence Banks. ICGEB Director-General Group Leader, Tumour Virology International Centre for Genetic Engineering and Biotechnology Padriciano 99 34149 Trieste, Italy

Human Papillomaviruses (HPVs) are major causes of human malignancy. They are responsible for almost all cervical cancers, plus a large number of other anogenital malignancies and a growing number of head and neck cancers. Whilst there are over 300 different HPV types, only a small subset, the so-called high risk types, are cancer-causing. The most prevalent of which are HPV-16 and HPV-18 which account for approximately 70% of all cervical cancers.

Our interests are focussed firstly in understanding the mechanisms by which HPVs gain entry into the target cell and traffic the incoming viral genomes to the nucleus where a new round of the viral life cycle can commence. A major feature of this infectious entry pathway is the recruitment, by a component of the viral capsid, of the cellular endocytic cargo sorting machinery. This recruitment facilitates lysosomal escape for the incoming viral genomes and allows subsequent trafficking to the trans golgi network. These studies have defined a highly conserved HPV entry mechanism and provides novel targets for blocking HPV infection. The other area of investigation centres on understanding why only certain HPV types cause cancer and how post translational modifications of the viral oncoproteins contributes to this process. We have defined major functions of the two oncoproteins, E6 and E7, which are essential for the ability of the virus to induce malignancy. Using genome editing approaches we have been able to identify specific post translational modifications which play essential roles in maintaining the malignant potential of cervical tumour derived cell lines. In addition, a unique class of cellular target proteins, which harbour PDZ domains, appear to play major roles in the ability of these viruses to cause cancer. Taken together these studies define novel potential therapeutic approaches for treating HPV induced malignancy.

january 14, 2020