Oncogenic Viruses


Viruses are dynamic factors that can produce a significant burden of suffering on the population. Despite many scientific advances for the prevention and treatment of viral diseases, the precise pathogenic mechanisms involved remained only partially understood. As in the Art of War, it is important to know yourself and the enemy so as not to be defeated, and this matches perfectly for viral infections and the pathological outcomes. Moreover, this highlights the importance to achieve a deep understanding of the cellular and viral biology and specially to explore the virus- infected cell interactions. In this sense, our group analyse the contribution of cellular and viral factors to viral pathogenesis using cellular and molecular methods. In addition, due to the relevance of the environment for the development and emergence of viral diseases in humans, we also conduct our studies with a Global Health approach.

Research Lines

Study of conserved mechanisms of viral pathogenesis for viruses of clinical impact

Oncogenic viruses contribute to 15-20% of tumors worldwide. Thus, one of our interests is based on the analysis of the mechanisms involved in viral carcinogenesis, with a focus on the Human Papillomavirus (HPV) associated with the development of cervical cancer. We carry out our studies considering the disruption of cell polarity and the disorganization of the intercellular junctions induced by different viruses, as well as their consequence in cell transformation. For a better understanding of these viral activities, we use traditional, histotypic and organotypic cell cultures. We focus on the viral interference on the expression of adherens (Disc large, DLG1) and tight (Partitioning defective 3, PAR3) junction proteins, whose expressions are altered in different tumors. In this way, the study of the alterations of the expression of these proteins using viral models is an important contribution to the understanding of common mechanisms of oncogenic development.
On the other hand, different non-oncogenic viruses also alter the expression of polarity proteins and intercellular junctions, and this could contribute to viral entry, transmission and dissemination with consequences in the development of pathologies. From this, we apply our experience to study viral pathogenesis for arboviruses of regional concern, such as the ZIKA virus.

Hepatitis E, an emerging zoonosis with a growing impact on Global Health

Zoonoses represent a risk to public health, evidenced by the spread of previously unknown human infectious diseases emerging from animal reservoirs. In this sense, the Hepatitis E virus (HEV) is one of the most common causative agents of hepatitis worldwide and the only one among the hepatitis viruses that presents a zoonotic transmission, from pigs, as one of the main reservoirs. Our group has demonstrated the circulation of the virus in commercial pig farms in Santa Fe, through the development of a diagnostic methodology with higher performance than those currently used in our environment. However, the true magnitude of the infection is still unknown, especially considering the existence of multifactorial conditions related to the dynamics and transmission routes of the virus within pig farms. This thus determines a risk for transmission to humans and an important health problem for populations at risk. We propose an interdisciplinary approach that allows for the comprehensive analysis of ANIMAL, ENVIRONMENTAL AND HUMAN HEALTH in our region, under a Global Health approach. We will investigate the viral circulation in samples from pigs and the environment, and the impact that this causes on populations at risk, immunosuppressed and with chronic liver diseases.

Selected Publications

  • Zoonotic transmission of hepatitis E virus in a pig farmer from Argentina: A case report. Zoonoses Public Health. 69(3):235-241. Acosta, J, Galimberti A,  Marziali F, Costaguta A, Bessone F, Tanno H, Gardiol D, Reggiardo MV, Cavatorta AL (2022). doi: 10.1111/zph.12902
  • Application of quantitative immunofluorescence assays to analyze the expression of cell contact proteins during Zika virus infections. Virus Research. 304, 198544.  Santiago L, Dizanzo MP, Fabbri C, Bugnon Valdano M, Luppo V, Levis S, Cavatorta AL, Morales MA, Daniela Gardiol. (2021). doi: 10.1016/j.virusres.2021.
  • HPV E6 and E7 oncoproteins cooperatively alter the expression of Disc Large 1 polarity protein in epithelial cells. BMC Cancer. 20(1):293. Dizanzo MP, Marziali F, Brunet Avalos C, Bugnon Valdano M, Leiva S, Cavatorta AL, Gardiol D (2020). doi: 10.1186/s12885-020-06778-5 .
  • Detection of HEV in naturally-infected swine from central Argentina by an optimized HEV/MS2 duplex RT-qPCR. Zoonoses Public Health 66(7):729-738. Marziali F, Acosta J, Bolatti E, Mirazo S, Skejich P, Silva P, Brassard J, Costaguta A, Gardiol D and Cavatorta AL. (2019). doi: 10.1111/zph.12620.
  • Differential expression of DLG1 as a common trait in different human diseases: an encouraging issue in molecular pathology. Biol Chem. 201; 400(6):699-710. Marziali, F; Dizanzo, MP., Cavatorta, AL and Gardiol, D. (2019). doi: 10.1515/hsz-2018-0350.
  • Interference of HTLV-1 Tax Protein with Cell Polarity Regulators: Defining the Subcellular Localization of the Tax-DLG1 Interaction. Viruses Basel 2017, 9, 355-374. Marziali F, Bugnon Valdano M, Brunet Avalos C, Moriena L, Cavatorta AL and Gardiol Daniela (2018). doi:10.3390/v9120355.
  • DLG1 polarity protein expression associates with the disease progress of low-grade cervical intraepithelial lesions. Experimental and Molecular Pathology, 102 65 –69. Cavatorta AL, Di Gregorio A, Valdano MB, Marziali F, Cabral M, Bottai H, Cittadini J, Nocito AL, Gardiol D. (2017). doi: 10.1016/j.yexmp.2016.12.008
  • Disc Large 1 expression is altered by Human Papillomavirus E7/E6 proteins in organotypic cultures of human keratinocytes. J Gen Virol. 2016 Feb;97(2):453-62. Bugnon Valdano, M; Cavatorta, AL; Morale, M; Marziali, F; de Souza Lino, V; Steenbergen, R; Boccardo, E and Gardiol (2016). doi: 10.1099/jgv.0.000364
  • Transcriptional and translational mechanisms contribute to regulate the expression of Disc Large 1 protein during different biological processes. Biological Chemistry, 396(8):893-902. Marziali F, Cavatorta AL, Bugnon Valdano M, Facciuto F and Gardiol D. (2015). doi: 10.1515/hsz-2014-0286
  • Human papillomavirus (HPV)-18 E6 oncoprotein interferes with the epithelial cell polarity Par3 protein. Molecular Oncology, 8:533-543. Facciuto F, Bugnon Valdano M, Marziali F, Massimi P, Banks L, Cavatorta AL and Gardiol D. (2014). doi: 10.1016/j.molonc.2014.01.002