CELL POLARITY PROTEINS AS COMMON TARGETS FOR VIRAL PATHOGENESIS

DANIELA GARDIOL

Congreso; Reunión Anual de la SAFIS 2019; 2019

SAFIS

Cellular polarity is maintained by the interconnected activity of polarity complexes whose components have a well-defined subcellular localization and, in addition, are key regulators of the intercellular junctions. Proteins derived from different viruses can interfere with the functions of polarity regulators, mainly the PDZ domain-containing proteins. These interferences result in significant biological alterations, important for virus entry, dissemination and pathogenesis.In our group, we have focused on the oncogenic mechanisms linked to polarity disruption during Human Papillomavirus (HPV) infections that are associated to the development of cervical cancer. We have characterized some of these cellular targets, such as the human Discs large oncosuppressor (DLG1) and the tight junction Partitioning defective 3 protein (PAR3). By diverse methodological tools, such as traditional, histotypical and organotypical raft cultures, we have evaluated the changes in the expression of these cell proteins mediated by HPV. Remarkably, clear alterations in the levels and the distribution along the epithelium, as well as in the subcellular localization, were observed for these proteins, particularly for DLG1. As these findings may entail the deregulation of cellular processes involved in tumour suppression, the data obtained have encouraged us to search for malignant progression biomarkers.We also extended our studies to other tumor viruses, such as the human T-cell lymphotropic virus type 1 (HTLV-1). By fluorescence microscopy we evaluated the aberrant accumulation of polarity regulators in vesicle-like structures, in the presence of the HTLV-1 Tax oncoprotein, with potential significance in lymphocyte deregulation and in the development of lymphoid pathologies. Moreover, disruption of cell polarity and alterations of intercellular contacts are not restricted to tumor viruses. As a result, we are currently interested in the analysis of these processes during infections by regional arboviruses, like the Zika virus, which has been associated with serious neurological and developmental pathologies.The knowledge about conserved mechanisms of viral pathogenesis could help to the understanding of basic viral biological processes and to the identification of special targets for novel diagnostic or therapeutic tools.