Conserved Mechanisms of Viral Pathogenesis: Alterations of cell polarity and intercellular junctions

DANIELA GARDIOL

Otro; Seminarios de Division of Molecular Medicine; 2017

Ruđer Bo?ković Institute, Zagreb

Conserved Mechanisms of Viral Pathogenesis: Alterations of cell polarity and intercellular junctions.Cellular polarity is due to the interconnected action of polarity complexes whose components have defined cell localization and are key regulators of the intercellular junctions. Proteins derived from different viruses can interact and interfere with the function of polarity proteins, in particular the PDZ domain-containing proteins, resulting in important functional alterations in various viral infectious processes.In our group, we have focused on the mechanisms of oncogenesis associated with Human Papillomavirus (HPV) infections from the point of view of polarity disruption. Thus, we have characterized some of these cellular targets, such as human Discs large and the tight junction Partitioning defective 3 protein. Through the use of different methodological tools, such as traditional, histotypical and organotypic raft cultures, we were able to evaluate the changes in the expression of these cell proteins mediated by the HPV oncoproteins. As these findings may entail the deregulation of cellular processes involved in tumour suppression, the data obtained has encouraged us to search for malignant progression biomarkers.In addition, we extended our studies to other tumor viruses, such as the human T-cell lymphotropic virus type 1 (HTLV-1). Using fluorescence microscopy we evaluated changes in the cell distribution of polarity regulators in the presence of the HTLV-1 Tax protein with potential significance in lymphocyte deregulation and the development of lymphoid pathologies.On the other hand, disruption of cell polarity and alterations of cell-to-cell contacts are not limited to oncogenic viruses. Thus, one of the group's current interests consists in translating this experience into the analysis of pathogenic mechanisms associated with infections by regional arboviruses.