Molecular virology

Andrea V. Gamarnik - Fundación Instituto Leloir

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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.
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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





Andrea V. Gamarnik
Head of Laboratory - agamarnik@leloir.org.ar



Ezequiel Aranovich
Becario Doctoral Agencia



Laura Byk
PhD student - CONICET fellowship



Luana De Borba
Postdoctoral fellow



Federico De Maio
Postdoctoral fellow



Claudia Filomatori
Research Associate



Leopoldo Gebhard
Research Associate



Néstor Gabriel Iglesias
Research Associate



Sergio Villordo
PhD student - CONICET fellowship