ICGEB - Tumour Virology Lab
Human Papillomaviruses (HPVs) are the causative agents of a number of human tumours, including cervical cancer, which is the major cause of cancer related death in women in many parts of the developing world. The development of these tumours requires the action of two viral oncoproteins, E6 and E7: understanding the mechanism of action of these two HPV gene products is one of the major aims of the laboratory. The work has focused on identifying the cellular targets of the viral oncoproteins and we are now dissecting the effects of these proteins upon important cellular regulatory pathways. Current major interests include the cell polarity regulators Discs Large and Scribble, both of which are potential tumour suppressor proteins. Indeed, perturbation of cell polarity regulation appears to be a common theme in many tumours caused by different human cancer-causing viruses . The laboratory is also aiming to develop novel therapeutics directed against E6 and studies are also in progress aiming to more fully understand the function of the E6 associated ubiquitin ligase (E6AP). Recent work has also begun to investigate the mechanisms by which HPVs enter the target cell, with emphasis being placed on dissecting the function of the minor capsid protein L2. Using proteomic approaches we have identified some of the critical events that take place during virus infection, and in particular the roles played by the endosomal sorting machinery, as exemplified by sorting nexins. Current studies are aimed at understanding how sorting nexins aid viral escape from the late endsosmes, and how the viral L2 protein might, in turn, perturb the normal function of endosomal sorting pathways. The Group’s studies invariably require extensive molecular cell biological analyses of the viral target proteins, since in many cases these are themselves, only poorly understood. Thus, as has been seen with other DNA Tumour Virus models, HPV research offers unique insights into the processes affecting diverse and critical aspects of cell biology.