The laboratory studies the molecular mechanisms of the replication of dengue and Zika viruses. These viruses belong to the Flaviviridae family, whose members are viruses with a single-stranded, positive-polarity genome. The genome of dengue and Zika viruses have multiple functions during the viral cycle: it serves as a messenger for protein synthesis, a template for the amplification of RNA and a substrate for encapsidation during the formation of viral particles. The laboratory studies focus on understanding how the viral genome works, taking into account that it is a dynamic molecule that changes its conformation in the different viral processes. For this, the use of reverse genetics and manipulation of infectious clones is combined with biochemical studies.

• Study of the function, dynamics and adaptation of dengue and Zika virus RNA during replication in human and mosquito cells.
• Development of molecular tools to genetically manipulate the dengue and Zika virus that may be useful for the design of antiviral strategies.
• Study of the mechanism of RNA encapsidation and function of the capsid protein during the morphogenesis of the dengue virus.
• Study of the properties and functions of the capsid protein of Dengue and Zika viruses during infection in the search for new approaches in the development of antiviral strategies.
• Study of the interactions between the NS5 protein of dengue and Zika virus with host proteins as a mechanism of evasion of the cellular antiviral response.

RNA structure duplication in the dengue virus 3’UTR: redundancy or host specificity? de Borba L, Villordo SM, Marsico FL, Carballeda JM, Filomatori CV, Gebhard LG, Pallarés HM, Lequime S, Lambrechts L, Sánchez Vargas I, Blair CD, Gamarnik AV. MBio. 2019, 10:e02506-18. PubMed

Dengue virus genomic variation associated with mosquito adaptation defines the pattern of viral non-coding RNAs and fitness in human cells. Filomatori CV, Carballeda JM, Villordo SM, Aguirre S, Pallarés HM, Maestre AM, Sánchez-Vargas I, Blair CD, Fabri C, Morales MA, Fernandez-Sesma A, Gamarnik AV. PLoS Pathog. 2017 Mar 6;13(3):e1006265. PubMed

The Dengue Virus NS5 Protein Intrudes in the Cellular Spliceosome and Modulates Splicing. De Maio FA, Risso G, Iglesias NG, Shah P, Pozzi B, Gebhard LG, Mammi P, Mancini E, Yanovsky MJ, Andino R, Krogan N, Srebrow A, Gamarnik AV. PLoS Pathog. 2016 Aug 30;12(8):e1005841. PubMed

Properties and Functions of the Dengue Virus Capsid Protein. Byk LA, Gamarnik AV. Annu Rev Virol. 2016 Sep 29;3(1):263-281

Dengue Virus Genome Uncoating Requires Ubiquitination. Byk LA, Iglesias NG, De Maio FA, Gebhard LG, Rossi M, Gamarnik AV. MBio. 2016 Jun 28;7(3). pii: e00804-16. PubMed

A Proline-Rich N-Terminal Region of the Dengue Virus NS3 Is Crucial for Infectious Particle Production. Gebhard LG, Iglesias NG, Byk LA, Filomatori CV, De Maio FA, Gamarnik AV. J Virol. 2016 May 12;90(11):5451-61. PubMed

RNA Structure Duplications and Flavivirus Host Adaptation. Villordo SM, Carballeda JM, Filomatori CV, Gamarnik AV. Trends Microbiol. 2016 Apr;24(4):270-283. PubMed

Dengue Virus Uses a Non-Canonical Function of the Host GBF1-Arf-COPI System for Capsid Protein Accumulation on Lipid Droplets. Iglesias NG, Mondotte JA, Byk LA, De Maio FA, Samsa MM, Alvarez C, Gamarnik AV. Traffic. 2015 Sep;16(9):962-77. PubMed

Dengue virus RNA structure specialization facilitates host adaptation. Villordo SM, Filomatori CV, Sánchez-Vargas I, Blair CD, Gamarnik AV. PLoS Pathog. 2015 Jan 30;11(1):e1004604. PubMed

Overlapping local and long-range RNA-RNA interactions modulate dengue virus genome cyclization and replication. de Borba L, Villordo SM, Iglesias NG, Filomatori CV, Gebhard LG, Gamarnik AV. J Virol. 2015 Mar;89(6):3430-7. PubMed

11. Monomeric nature of dengue virus NS3 helicase and thermodynamic analysis of the interaction with single-stranded RNA. Gebhard LG, Incicco JJ, Smal C, Gallo M, Gamarnik AV, Kaufman SB. Nucleic Acids Res. 2014 Oct;42(18):11668-86. PubMed

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