Source: Interfolio F180
Juan C. De La Torre, PhD
Research Focus
Work in our laboratory focuses on the investigation of the molecular and cell biology of mammarenaviruses (Order Bunyavirales) and their biological implications. Mammarenaviruses are enveloped viruses with a bi-segmented negative-strand RNA genome. The prototypic mammarenavirus lymphocytic choriomeningitis virus (LCMV)provides investigators with a highly tractable experimental model system for the investigation of virus-host interactions and associated diseases. Moreover, several mammarenaviruses cause severe disease in humans and pose important public health threats. We pioneered the development of a reverse genetics system for the prototypic mammarenavirus lymphocytic choriomeningitis virus (LCMV) and subsequently developed similar systems for the HF-causing mammarenaviruses Lassa (LASV) and Junin (JUNV) viruses. The development of mammarenavirus reverse genetics has provided us with a powerful approach for the investigation of the cis-acting sequences and trans-acting factors that control mammarenavirus replication and gene expression, as well as assembly and budding. Moreover, our ability to rescue infectious mammarenaviruses entirely from cloned cDNAs allows us to examine the phenotypes of recombinant mammarenaviruses with predetermined mutations of interest in the context of the virus's natural infection. These advances in mammarenavirus molecular genetics have allowed us to develop a variety of cell-based assays and tools to identify and functionally characterize virus-host cell protein interactions, as well as the identification and characterization of inhibitors of mammarenavirus multiplication, including the HF-causing LASV and JUNV. In addition, we have leveraged our findings on the molecular and cell biology of mammarenaviruses to generate recombinant (r) forms of LCMV and LASV that are fully attenuated in animal models of LCMV and LASV infections, and able to provide complete protection, upon a single administration, against a lethal challenge with the corresponding wild-type forms of LCMV or LASV. These novel rLASV represent attractive novel live-attenuated vaccine candidates to combat human pathogenic mammarenaviruses.
Education
Ph.D., Autonomous University of Madrid, 1985Professional Experience
1989-1991 Research Associate1991-1991 Research Associate Sr
1991-1996 Assistant Professor
1996-2009 Associate Professor
2009-Present Professor
Awards & Professional Activities
Juan March Postdoctoral Fellowship 1981 – 1985CSIE Postdoctoral Fellowship 1985-1987
NATO Postdoctoral Fellowship 1987-1988
Fulbright Postdoctoral Fellowship 1988 - 1990
1995 Spanish Society of Virology Award
Japanese Science Foundation Award 1997
Editorial Board: J. Virology; Virology and J. General Virology.
Charted Member (October 2003-June 2006) Virology B (VIRB) Study Section, NIH.
Charted Member (October 2009-2013) Virology B (VIRB) Study Section, NIH.
Charted Member (August 2019-Present) MID Study Section, NIH.
Ad Hoc Reviewer for several NIH Study Sections, and international funding agencies.
Member of the TSRI IACUC (2003-present), Chairperson Since 2005.
Member TSRI Institutional Bio-safety Committee (IBC) (1999-Present), Chairperson Since December 2019
Selected Publications
Sanchez, A. B.; de la Torre, Juan C. Rescue of the prototypic arenavirus LCMV entirely from plasmid. Virology 2006, 350, 370-380.
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Emonet, Sebastien F.; Garidou, Lucile; McGavern, Dorian B.; de la Torre, Juan C.
Generation of recombinant lymphocytic choriomeningitis viruses with trisegmented genomes stably expressing two additional genes of interest
. Proceedings of the National Academy of Sciences 2009, 106, 3473-3478.[View]
Martinez-Sobrido, L.; Emonet, S.; Giannakas, P.; Cubitt, B.; Garcia-Sastre, A.; de la Torre, Juan C. Identification of amino acid residues critical for the anti-interferon activity of the nucleoprotein of the prototypic arenavirus lymphocytic choriomeningitis virus. Journal of Virology 2009, 83, 11330-11340.
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Fang, Jingru; Pietzsch, Colette; Witwit, Haydar; Tsaprailis, George; Crynen, Gogce; Cho, Kelvin F.; Ting, Alice Y.; Bukreyev, Alexander; Saphire, Erica O.; de la Torre, Juan C. Proximity interactome analysis of Lassa polymerase reveals eRF3a/GSPT1 as a druggable target for host-directed antivirals. 2022, 119, e2201208119.
Sakabe, Saori; Cubitt, Beatrice; Martinez-Sobrido, Luis; de la Torre, Juan C.
Molecular Engineering of a Mammarenavirus with Unbreachable Attenuation
. Journal of Virology 2023, 97.[View]