engleski

Human papillomaviruses: From Infectious Entry to Malignancy

Human Papillomaviruses (HPVs) are major causative agents of human malignancies with cervical cancer being the most important. The virus infects differentiating epithelia where its life cycle is strictly dependent upon epithelial cell differentiation. Under normal circumstances the majority of these infections are self-limiting and cleared by the immune system. However, in rare cases infection can persist and this can ultimately result in the development of malignancy. Two major viral oncoproteins, E6 and E7, are critical for development and maintenance of malignant phenotype. Both of these oncoproteins interfere with crucial cellular pathways that are essential in maintaining cellular homeostasis. These viral activities are necessary for establishing an environment which can support the normal viral life cycle, however when perturbed, can initiate accumulation of changes to the host cell, which can ultimately lead to the development of a malignancy. The importance of E6 and E7 in maintaining transformed cellular phenotype can be clearly observed from the fact that they continue to be expressed in HPV-tumors and derived cells lines numerous years after the primary immortalizing events. This was supported by many studies which showed that any interference with these oncogenes at either the transcriptional or post translational levels results in cell growth arrest and/or apoptosis. Therefore, E6 and E7 represent excellent targets for any therapeutic intervention, and thus the major focus of our current research is on better understanding the molecular mechanisms underlaying their respective functions which could help in developing novel antiviral therapies.

HPV ; cancer ; E6 and E7 oncoproteins

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