The main goal of the laboratory is to understand how viral RNAs communicate with the host cell machinery and other viral components to ensure viral replication. In our research, we are using dengue virus as a model because it is one of the most important human viral pathogens of our times. Pathogenic RNA viruses, including HIV, SARS, dengue and influenza, have been the cause of the largest epidemics worldwide. Currently, neither vaccines nor antiviral drugs exist to control dengue virus infections. Our main goal is to generate knowledge and new tools to rationally design antiviral strategies.
To this end, we combine biochemistry, molecular biology, and biophysics, together with classical and molecular virology studies. We use infectious dengue virus clones and manipulation of the viral genome to define the function of RNA structures and viral proteins. Using these tools in infected cells and employing reconstituted in vitro systems, we are investigating the mechanism of viral genome amplification and the process of genome encapsidation.
The laboratory has made important contributions to the current knowledge of the dengue virus biology, and has developed new genetic tools to address basic questions of the viral life cycle.
Gebhard LG, Kauffman S., Gamarnik A. Novel ATP-independent RNA Annealing Activity of the Dengue Virus NS3 Helicase. PLoS ONE, 2012;7(4):e36244. Epub 2012 Apr 30.
PubMed
Samsa M, Mondotte J, Caramelo J, Gamarnik A. Uncoupling cis-Acting RNA elements from coding sequences revealed a requirement of the N-terminal region of dengue virus capsid protein in virus particle formation. Journal of Virology, 2012 Jan;86(2):1046-58
PubMed
Gebhard LG, Filomatori CV, Gamarnik A. Functional RNA elements in the dengue virus genome. Viruses. 2011 Sep;3(9):1739-56.
PubMed
Iglesias NG, Gamarnik A. Dynamic RNA structures in the dengue virus genome. RNA Biol. 2011 Mar-Apr;8(2):249-57.
PubMed
Iglesias G, Filomatori C, and Gamarnik AV F1 Motif of Dengue Virus Polymerase NS5 Is Involved in Promoter-Dependent RNA Synthesis, Journal of Virology 2011, Jun;85(12):5745-56.
PubMed
Filomatori, C.V., Iglesias, N.G., Villordo, S.M., Alvarez, D.E., Gamarnik, A.V. RNA sequences and structures required for the recruitment and activity of the dengue virus polymerase. J Biol Chem. (en prensa). PubMed
Villordo, S.M., Alvarez, D.E., Gamarnik, A.V. A balance between circular and linear forms of the dengue virus genome is crucial for viral replication. RNA. 16: 2325-2335 (2010). PubMed
Samsa, M.M., Mondotte, J.A., Iglesias, N.G., Assunção-Miranda, I., Barbosa-Lima, G., Da Poian, A.T., Bozza, P.T.,Gamarnik, A.V. Dengue virus capsid protein usurps lipid droplets for viral particle formation. PLoS Pathog. 5:e1000632 (2009) PubMed
Lodeiro, M.F., Filomatori, C.V., Gamarnik, A.V. Structural and functional studies of the promoter element for dengue virus RNA replication.(2009) Journal of Virology, Jan;83(2):993-1008. PubMed
Villordo, S.M., Gamarnik, A.V. Genome cyclization as strategy for flavivirus RNA replication. Virus Res. 139:230-239 (2009). Review PubMed
Alvarez, D.E., Filomatori, C.V., Gamarnik, A.V. Functional analysis of dengue virus cyclization sequences located at the 5 ' and 3 ' UTRs. Virology. 375:223-235 (2008). PubMed
Mondotte, J.A., Lozach, P.Y., Amara A., Gamarnik, A.V. Essential role of dengue virus envelope protein N glycosylation at asparagine-67 during viral propagation. J Virol. 81:7136-7148 (2007). PubMed
Alvarez, D., Lodeiro, M.F., Filomatori, C., Fucito, S., Mondotte, J. Gamarnik, A. Structural and functional análisis of dengue virus RNA. Novartis Found. Symp. 277:120-132 (2006). Review PubMed
Filomatori, C.V., Lodeiro, M.F., Álvarez, D.E., Samsa, M.M., Pietrasanta, L., Gamarnik, A.V. A 5’ RNA Element Promotes Dengue Virus RNA Synthesis on a Circular Genome. Gene Dev. 20: 2238-2249 (2006). PubMed
Melino, S., Fucito, S., Campagna, A., Wrubl, F., Gamarnik, A., Cicero, D., Paci, M. The active essential CFNS3d protein complex. FEBS J. 273: 3650-3662 (2006). PubMed
Álvarez, D.E., Lodeiro, M.F., Ludueña, S.J., Pietrasanta, L.I., Gamarnik, A.V. Long-range RNA-RNA interactions circularize the dengue virus genome. J. Virol. 79: 6631-6643 (2005). PubMed
Czibener, C., Scodeller, E., Gamarnik, A.V. Characterization of internal ribosomal entry sites of Triatoma virus. J. Gen. Virol. 86: 2275-2280 (2005). PubMed
Diego Alvarez, Ana Laura De Lella Ezcurra, Silvana Fucito, Gamarnik, A.V. Role of RNA Structures Present at the 3’UTR of Dengue Virus on Translation, RNA Synthesis, and Viral Replication. Virology Sep 1;339(2):200-12 (2005). PubMed
