Researh & development

Molecular Virology

Profile

Viruses infect all domains of life and have an important role in public health and evolution. We follow basic questions related to the viral biology of infection, with special focus on the envelope proteins of viruses, which they use to enter and exit cells. Therefore we use as model systems the human pathogenic hantaviruses and also membrane-containing archaeal viruses. For hantaviruses we have provided molecular insights into its virus:cell membrane fusion mechanism and characterized the organization and dynamics of the fusion protein Gc on the viral surface. For the design of vaccine and drug candidates we also focus on protective immune responses against hantavirus, using non-replicative virus-like particles developed previously by us. Based on our experience with the fusion protein of animal-infecting hantaviruses, we have identified the fusion activity of enveloped halophilic archaeal viruses (pleolipoviruses). We expect that future mechanistic information will allow us to unveil how viruses modulate archaeal membranes in this yet poorly explored life domain.

  • Doctoral Students: Fabian Figueroa, Javier Díaz
  • Undergraduate Students: Esteban Rodriguez, Simone Cárdenas
  • Research Assistants: Gianina Alessan, Kevin Chou
  • Post-doctoral Fellows: Nicolás Muena
  • Research Associates: Amelina Albornoz, Eduardo Bignon

Former PhD studentes:
• Nicolás Cifuentes-Muñoz (2006-2011). Assistant Professor at Universidad Autónoma de Chile
• Gonzalo Barriga (2009-2014). Assistant Professor at University of Chile
• Rodrigo Acuña (2009-2015). Teaching Researcher, Universidad del Desarrollo de Chile
• María Pía García (2012-2019). Regulatory affairs exports, Drag Pharma Laboratory Invetec S.A., Chile

Former Master & undergraduate students:
• Simón Vidal (2008-2009). Post-doctoral researcher at Genentech, USA
• Ana Elola (2012-2014). Director of scientific education, Co-founder of BioClass, Chile
• Fernando Villalón (2010–2011 & 2011-2014 RA). PhD student, University of Melbourne, Australia
• Anke Roder, (2009-2010). Research Specialist at Procter & Gamble, Germany
• Chantal Márquez (2012-2014). Post-doctoral researcher, Universidad de Chile
• Natalia Salazar-Quiroz (2012-2014). PhD student, University of Melbourne, Australia
• Vicente Muñoz (2014-2016). PhD student, Universidad de Chile

National Collaborations
• Dr. Alejandro Rojas, Universidad Austral, Chile
• Dr. Fernando Torrés-Perez, Universidad Católica de Valparaiso, Chile
• Dr. Marcela Ferrés, Pontificia Universidad Católica de Chile
• Dr. Marcelo López-Lastra & Dr Jorge Vera-Otarola, Pontificia Universidad Católica de Chile
• Dr. Rafael Medina, Pontificia Universidad Católica de Chile

International Collaborations
• Dr. Elina Roine; Dr Juha Huiskonen, Helsinki University, Finland
• Dr. Félix Rey & Dr Pablo Guardado-Calvo, Pasteur Institut, France
• Dr. Jay Hooper, USAMRIID, USA
• Dr. Juan Reguera, AFMB, Aix-Marseille University/CNRS, France
• Dr. Kartik Chandran & Dr Rohit Jangra, Albert Einstein College of Medicine, USA
• Dr. Pierre-Yves Lozach, University Hospital Heidelberg, Germany; University Claude Bernard, France
• Dr. Salvatore Chiantia, Potsdam Universität, Germany
• Dr. Susanne Erdmann, Max Planck Institut Bremen, Germany

Publications

Albornoz A, Hoffmann AB, Lozach PY*, Tischler ND* (2016).Early Bunyavirus-Host Cell Interactions. Viruses 24;8(5). doi: 10.3390/v8050143

Barriga GP, Villalón-Letelier F, Márquez CL, Bignon EA, Acuña R, Ross BH, Monasterio O, Mardones GA, Vidal SE, Tischler ND* (2016).Inhibition of the Hantavirus Fusion Process by Predicted Domain III and Stem Peptides from Glycoprotein Gc. PLoS Negl. Trop. Dis. 10(7):e0004799. doi: 10.1371/journal.pntd.0004799

Willensky, S, Bar-Rogovsky, H, Bignon, EA, Tischler, ND, Modis, Y., Dessau, M.* (2016).Crystal Structure of Glycoprotein C from a Hantavirus in the Post-fusion Conformation. PLoS Path. 12(10):e1005948. doi: 10.1371/journal.ppat.1005948

Guardado-Calvo P, Bignon EA, Stettner E, Jeffers SA, Pehau-Arnaudet G, Tortorici MA, Jestin JL, England P, Tischler ND*, Rey FA* (2016). Mechanistic insight into bunyavirus-induced membrane 1 fusion from structure-function analyses of the hantavirus envelope glycoprotein Gc. PLoS Path. 12(10):e1005813. doi: 10.1371/journal.ppat.1005813

Jangra, RK; Herbert, AS; Li, R.; Jae, LT; Kleinfelter, LM; Slough, MM; Barker, SL; Guardado-Calvo, P; Román-Sosa, R; Dieterle, ME; Kuehne, AI; Muena, NA; Wirchnianski, AS; Nyakatura, EK; Fels, JM; Ng, M; Mittler, E; Pan, J.; Bharrhan, S; Wec, AZ; Lai, JR; Sidhu, SS; Tischler, ND; Rey, FA; Moffat, J; Brummelkamp, TR*; Wang, Z*; Dye, JM*; Chandran, K* (2018). Protocadherin-1 is critical for cell entry by New-World hantaviruses. Nature 563(7732):559-563. doi: 10.1038/s41586-018-0702-1

El Omari, K, Li, S, Kotecha, A, Walter, TS; Bignon EA; Harlos, K; Somerharju, P; De Haas, F; Clare DK; Molin, M; Hurtado, F; Li, M; Grimes, JM; Bamford, DH; Tischler, ND*; Huiskonen, JT*; Stuart, DI*; Roine, E.* (2019). The structure of a prokaryotic viral envelope protein expands the landscape of membrane fusion proteins. Nature Com, 10(1):846. doi: 10.1038/s41467-019-08728-7.

Bignon EA, Albornoz A, Guardado-Calvo P, Rey FA*, Tischler ND* (2019). Molecular organization and dynamics of the fusion protein Gc at the hantavirus surface. eLife 8. pii: e46028. doi: 10.7554/eLife.46028.

Serris A, Stass R, Bignon EA, Muena NA, Manuguerra JC, Jangra RK, Li S, Chandran K, Tischler ND, Huiskonen JT, Rey FA, Guardado-Calvo P. (2020) High-Resolution Description of the Hantavirus Surface Glycoprotein Lattice and Its Membrane Fusion Control Mechanism. Cell 183:1-15 doi: 10.1016/j.cell.2020.08.023

Bignon, E.A.; Chou, K.R.; Roine, E.; Tischler, N.D*. (2022). Halorubrum Pleomorphic Virus 6 Membrane Fusion Is Triggered by an S-Layer Component of Its Haloarchaeal Host. Viruses, 14(2):254. doi: 10.3390/v14020254.

Muena NA, García-Salum T, Pardo-Roa C, Serrano EF, Levican J, Avendaño MJ, Almonacid LI, Valenzuela G, Poblete E, Strohmeier S, Salinas E, Haslwanter D, Dieterle ME, Jangra RK, Chandran K, González C, Riquelme A, Krammer F, Tischler ND*, Medina RA*. Induction of SARS-CoV-2 neutralizing antibodies by CoronaVac and BNT162b2 vaccines in naïve and previously infected individuals. EBioMedicine 78:103972. doi: 10.1016/j.ebiom.2022.103972.

Cifuentes-Muñoz N, Salazar-Quiroz N, Tischler ND (2014). Hantavirus Gn and Gc envelope glycoproteins: structural key units for virus cell entry and virus assembly. Viruses, vol. 21,6(4):1801–22 doi: 10.3390/v6041801 | PDF

Acuña R, Cifuentes-Muñoz N, Márquez CL, Bulling M, Klingström J, Mancini R, Lozach PY, Tischler, ND (2014). Hantavirus Gn and Gc glycoproteins self-assemble into virus-like particles . Journal of Virology, vol. 88(4):2344-2348. doi: 10.1099/jgv.0.000269 | PDF

Acuña R., Bignon E.A., Mancini R., Lozach P.Y., Tischler N.D. (2015). Acidification triggers Andes hantavirus membrane fusion and rearrangement of Gc into a stable post-fusion homotrimer. J Gen Virol. 96(11):3192-7. doi: 10.1099/jgv.0.000269 | PDF

Barriga GP, Villalón-Letelier F, Márquez CL, Bignon EA, Acuña R, Ross BH, Monasterio O, Mardones GA, Vidal SE, Tischler ND (2016). Inhibition of the hantavirus fusion process by predicted domain III and stem peptides from glycoprotein Gc. PLoS Negl Trop Dis 10(7), e0004799. doi: 10.1371/journal.pntd.0004799 | PDF

Albornoz A, Hoffmann AB, Lozach PY, Tischler ND (2016). Early Bunyavirus-host cell interactions. Viruses 24;8(5). doi: 10.3390/v8050143 | PDF

Willensky, S, Bar-Rogovsky, H, Bignon, EA, Tischler, ND, Modis, Y, Dessau, M* (2016). Crystal Structure of Glycoprotein C from a Hantavirus in the Post-fusion Conformation. PLoS Path 12(10):e1005948. doi: 10.1371/journal.ppat.1005948 | PDF

Guardado-Calvo, P, Bignon, EA, Stettner, E, Jeffers SA, Pehau-Arnaudet, G, Tortorici, MA, Jestin, JL, England, P, Tischler, ND*, Rey, FA* (2016). Mechanistic insight into bunyavirus-induced membrane 1 fusion from structure-function analyses of the hantavirus envelope glycoprotein Gc. PLoS Path 12(10):e1005813. doi: 10.1371/journal.ppat.1005813. | PDF

Jangra, RK; Herbert, AS; Li, R.; Jae, LT; Kleinfelter, LM; Slough, MM; Barker, SL; Guardado-Calvo, P; Román-Sosa, R; Dieterle, ME; Kuehne, AI; Muena, NA; Wirchnianski, AS; Nyakatura, EK; Fels, JM; Ng, M; Mittler, E; Pan, J.; Bharrhan, S; Wec, AZ; Lai, JR; Sidhu, SS; Tischler, ND; Rey, FA; Moffat, J; Brummelkamp, TR*; Wang, Z*; Dye, JM*; Chandran, K* (2018). Protocadherin-1 is critical for cell entry by New-World hantaviruses. Nature 563(7732):559-563. doi: 10.1038/s41586-018-0702-1 | PDF

El Omari, K, Li, S, Kotecha, A, Walter, TS; Bignon EA; Harlos, K; Somerharju, P; De Haas, F; Clare DK; Molin, M; Hurtado, F; Li, M; Grimes, JM; Bamford, DH; Tischler, ND*; Huiskonen, JT*; Stuart, DI*; Roine, E.* (2019). The structure of a prokaryotic viral envelope protein expands the landscape of membrane fusion proteins. Nature Com, 10(1):846. doi: 10.1038/s41467-019-08728-7. | PDF

Bignon, EA, Albornoz, A, Guardado-Calvo, P, Rey, FA*, Tischler, ND* (2019). Molecular organization and dynamics of the fusion protein Gc at the hantavirus surface. eLife e46028. doi: 10.7554/eLife.46028 | PDF

Uckeley ZM, Koch J, Tischler ND, Léger P, Lozach PY*. Cell biology of phlebovirus entry. Virologie (Montrouge). 2019 Jun 1;23(3):176-187. doi: 10.1684/vir.2019.0780. | PDF

Carrasco M*, Toledo P, Tischler ND. (2019) Biomolecules 9(12). pii: E809. doi: 10.3390/biom9120809Macromolecule Particle Picking and Segmentation of a KLH Database by Unsupervised Cryo-EM Image Processing. | PDF

Clement J*, Ahlm C, Avšič-Županc T, Botten J, Chandran K, Jonsson CB, Kariwa H, Klingström J, Klempa B, Krüger DH, Leirs H, Li D, Liang M, Markotić A, Papa A, Schmaljohn CS, Tischler ND, Ulrich RG, Vaheri A, Vial C, Yanagihara R, Maes P. (2020) Meeting report: Eleventh International Conference on Hantaviruses. Antiviral Res. 176:104733. doi: 10.1016/j.antiviral.2020.104733. | PDF

Otarola JV*, Solis L, Lowy F, Olguín V, Angulo J, Pino K, Tischler ND, Otth C, Padula P, López-Lastra M* (2020). The Andes orthohantavirus NSs protein antagonizes the type I interferon response by inhibiting MAVS signaling. J Virol. 00454-202020 doi: 10.1128/JVI.00454-20. | PDF

Ferrés M*, Martínez-Valdebenito C, Angulo J, Henríquez C, Vera-Otárola J, Vergara MJ, Pérez J, Fernández J, Sotomayor V, Valdés MF, González-Candia D, Tischler ND, Vial C, Vial P, Mertz G, Le Corre N* (2020). Mother-to-Child Transmission of Andes Virus through Breast Milk. Emerg Infect Dis 26(8):1885-1888. doi: 10.3201/eid2608.200204. | PDF

Serris A, Stass R, Bignon EA, Muena NA, Manuguerra JC, Jangra RK, Li S, Chandran K, Tischler ND, Huiskonen JT, Rey FA, Guardado-Calvo P. (2020) High-Resolution Description of the Hantavirus Surface Glycoprotein Lattice and Its Membrane Fusion Control Mechanism. Cell 183:1-15 doi: 10.1016/j.cell.2020.08.023 | PDF

Principal investigator

Nicole Tischler, PhD

+ 56 2 3672015

ntischler@cienciavida.org

Biography

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