CONSERVED MECHANISMS OF VIRAL PATHOGENESIS: ALTERATIONS OF CELL POLARITY AND INTERCELLULAR JUNCTIONS

DANIELA GARDIOL

PAANÁ

Congreso; LIV Reunión Annual de SAIB; 2018

Cellular polarity is maintained by the interconnected activity 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 functions of polarity cellular proteins, resulting in significant biological alterations, important for virus entry, dissemination and pathogenesis.Human papillomavirus (HPV) infections are associated with the development of cervical cancer. We have focused on the oncogenic viral mechanisms from the point of view of the polarity disruption. Thus, we have characterized some of these cellular targets, such as the human Discs large oncosuppressor (DLG1) and the tight junction Partitioning defective 3 protein. Through the use of different methodological tools, such as traditional, histotypical and organotypical raft cultures, we were able to evaluate the changes in the expression of these cell proteins mediated by HPV. In particular, DLG1 not only regulates cell junctions and polarity, but also cell proliferation and migration. Remarkably, clear alterations in the levels and the distribution along the epithelium, as well as in the subcellular localization, were observed for this protein. The data obtained has encouraged us to analyzing the differential expression of DLG1 as a potential progression biomarker in HPV-associated cervical lesions.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 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, we could show for the first time the interaction between a viral and a polarity protein within the cell, using FRET methodology. On the other hand, disruption of cell polarity and alterations of the cell-to-cell contacts are not limited to tumor viruses. Thus, one of the group´s current interests consists in the analysis of these processes during infections by regional arboviruses, mainly the Zika virus.The understanding of common mechanisms in viral pathogenesis could help not only for the comprehension of basic viral biology but also for the identification of special targets for novel diagnostic and therapeutic tools.