Experimental Evolution of Viruses

Epidemics caused by viruses cause millions of infections each year, putting thousands of lives at risk. The development of treatments frequently fails due to the great capacity of these pathogens to evade the immune response, in part as a consequence of their high mutation rates. Our lab studies viral evolution using experimental approaches to understand how viruses change in action.

The main objective is to understand how the genetic information of a virus determines its ability to replicate, transmit and virulence. We will also test evolutionary hypotheses to learn how viruses jump from one species to another and adapt to new hosts.

These experiments will be carried out through the use of synthetic biology in order to specifically alter, through genetic modifications, the replicative and/or transmission properties of the viruses that will be studied.

Our focus of study will be viruses which genomes are made up of RNA. We will mainly focus on viruses transmitted by arthropods (called arboviruses) and within these, those that use mosquito vectors such as dengue or zika. We will also investigate enteroviruses that can potentially emerge and cause a similar problem, such as the Mayaro virus, in order to be better prepared for future epidemics.

Members

Gonzalo Moratorio, PhD

Gonzalo Moratorio, PhD

Head

Faculty of Science, Udelar
moratorio@pasteur.edu.uy

Pilar Moreno, PhD

Pilar Moreno, PhD

Honorary researcher

Faculty of Science, Udelar
pmoreno@pasteur.edu.uy

Marianoel Pereira, PhD

Marianoel Pereira, PhD

Research assistant

Postdoctoral student
mnpereira@pasteur.edu.uy

Diego Simón, BSc

Diego Simón, BSc

Doctoral student

Faculty of Science, Udelar
dsimon@pasteur.edu.uy

Fabián Aldunate, MSc

Fabián Aldunate, MSc

Doctoral student

Faculty of Science, Udelar
faldunate@pasteur.edu.uy

Joaquín Hurtado, MSc

Joaquín Hurtado, MSc

Doctoral student

Faculty of Science, Udelar
jhurtado@pasteur.edu.uy

Rodrigo Arce, BSc

Rodrigo Arce, BSc

Research assistant

Master’s degree student
rarce@pasteur.edu.uy

Alicia Costábile, PhD

Alicia Costábile, PhD

Technical assistant

Álvaro Fajardo, PhD

Álvaro Fajardo, PhD

Honorary associate researcher

Faculty of Science, Udelar
afajardo@pasteur.edu.uy

Irene Ferreiro, BSc

Irene Ferreiro, BSc

Master's degree student

Natalia Echeverría, PhD

Natalia Echeverría, PhD

Research assistant

Mercedes Paz, BSc

Mercedes Paz, BSc

Technical assistant

Paula Perbolianachis, MSc

Paula Perbolianachis, MSc

Doctoral student

Faculty of Science, Udelar
perbolianachis@pasteur.edu.uy

Research lines

Restriction of the evolutionary potential of arboviruses through synthetic biology.

Study of the buffering capacity of mutations (genetic robustness) of RNA viruses.

Use of genetically modified enteroviruses as potential oncolytic agents.

Courses

  • PEDECIBA postgraduate course: «Mechanisms of viral translation and production: Introduction to transcription and translation in vitro and ex vivo». 9-13 March, 2020. Institut Pasteur de Montevideo, Faculty of Science (Udelar).

Projects

2020-2023 – “Attenuation of emerging arboviruses: synthetic biology and experimental evolution”. . Head: Gonzalo Moratorio. FCE-ANII.

2020-2023 – “Mutational robustness of RNA viruses”. Heads: Gonzalo Moratorio and Juan Cristina. FCE-ANII.

2019-2022 – “Understanding Arbovirus Emergence and Changing the Approach to Intervention”. Head IPmon: Gonzalo Moratorio. DARPA

Main publications

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2019
  • Cifuente JO, Moratorio G. Evolutionary and Structural Overview of Human Picornavirus Capsid Antibody Evasion. Front Cell Infect Microbiol. 2019 Aug 20;9:283. doi: 10.3389/fcimb.2019.00283. eCollection 2019. Review. PubMed PMID: 31482072; PubMed Central PMCID: PMC6710328.
  • Danet L, Beauclair G, Berthet M, Moratorio G, Gracias S, Tangy F, Choumet V, Jouvenet N. Midgut barriers prevent the replication and dissemination of the yellow fever vaccine in Aedes aegypti. PLoS Negl Trop Dis. 2019 Aug 14;13(8):e0007299. doi: 10.1371/journal.pntd.0007299. eCollection 2019 Aug. PubMed PMID: 31412040; PubMed Central PMCID: PMC6709925.
  • Carrau L, Rezelj VV, Noval MG, Levi LI, Megrian D, Blanc H, Weger-Lucarelli J, Moratorio G, Stapleford KA, Vignuzzi M. Chikungunya Virus Vaccine Candidates with Decreased Mutational Robustness Are Attenuated In Vivo and Have Compromised Transmissibility. J Virol. 2019 Aug 28;93(18). pii: e00775-19. doi: 10.1128/JVI.00775-19. Print 2019 Sep 15. PubMed PMID: 31270226; PubMed Central PMCID: PMC6714818.
  • Henningsson R, Moratorio G, Bordería AV, Vignuzzi M, Fontes M. DISSEQT-DIStribution-based modeling of SEQuence space Time dynamics. Virus Evol. 2019 Aug 5;5(2):vez028. doi: 10.1093/ve/vez028. eCollection 2019 Jul. Erratum in: Virus Evol. 2019 Nov 19;5(2):vez052. PubMed PMID: 31392032; PubMed Central PMCID: PMC6680062.
2018
  • Moratorio G, Vignuzzi M. Monitoring and redirecting virus evolution. PLoS Pathog. 2018 Jun 7;14(6):e1006979. doi: 10.1371/journal.ppat.1006979. eCollection 2018 Jun. PubMed PMID: 29879219; PubMed Central PMCID: PMC5991817.
  • Simón D, Fajardo A, Moreno P, Moratorio G, Cristina J. An Evolutionary Insight into Zika Virus Strains Isolated in the Latin American Region. Viruses. 2018 Dec 8;10(12). pii: E698. doi: 10.3390/v10120698. PubMed PMID: 30544785; PubMed Central PMCID: PMC6316622.
2017
  • Moratorio G, Henningsson R, Barbezange C, Carrau L, Bordería AV, Blanc H, Beaucourt S, Poirier EZ, Vallet T, Boussier J, Mounce BC, Fontes M, Vignuzzi M. Attenuation of RNA viruses by redirecting their evolution in sequence space. Nat Microbiol. 2017 Jun 5;2:17088. doi: 10.1038/nmicrobiol.2017.88. PubMed PMID: 28581455.