Replication, virus-host interactions, and protection in coronavirus

LEnjuanes

 Isabel Sola

Luis Enjuanes

Group Leader

Contact

 

Isabel Sola

Group Leader

Contact

 

 

 

Research summary

The main focus of our research is the study of the molecular basis of coronavirus (CoV) replication and virulence, and the identification of signalling pathways modified by the virus, to control disease. The information from these basic projects will be used to design protection strategies against CoV-induced diseases, particularly human severe pneumonia that can end in acute respiratory distress syndrome (ARDS).

 

Publications

Mateos-Gomez PA, Morales L, Zuñiga S, Enjuanes L, Sola I. Long-distance RNA-RNA interactions in the coronavirus genome form high-order structures promoting discontinuous RNA synthesis during transcription. J Virol 2013; 87:177-186

Almazan F, DeDiego ML, Sola I, Zuñiga S, Nieto-Torres JL, Marquez-Jurado S, Andres G, Enjuanes L. Engineering a replication-competent, propagation-defective Middle East respiratory syndrome coronavirus as a vaccine candidate. mBio 2013; 4:e00650-00613

DeDiego ML, Nieto-Torres JL, Regla-Nava JA, Jimenez-Guardeno JM, Fernandez-Delgado R, Fett C, Castano-Rodriguez C, Perlman S, Enjuanes L. Inhibition of NF-kappaB mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J Virol 2014; 88:913-924

Nieto-Torres JL, Dediego ML, Verdia-Baguena C, Jimenez-Guardeno JM, Regla-Nava JA, Fernandez-Delgado R, Castano-Rodriguez C, Alcaraz A, Torres J, Aguilella VM, Enjuanes L. Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis. PLoS Pathog 2014; 10:e1004077

Jimenez-Guardeno JM, Nieto-Torres JL, DeDiego ML, Regla-Nava JA, Fernandez-Delgado R, Castano-Rodriguez C, Enjuanes L. The PDZ-binding motif of severe acute respiratory syndrome coronavirus envelope protein is a determinant of viral pathogenesis. PLoS Pathog 2014; 10:e1004320

 

FigureEnjuanesHuman infections of the lower respiratory tract are a growing health problem. The annual number of hospital admissions due to pneumonia and acute respiratory disease syndrome was estimated during 2010 at 11.9 million worldwide. The problem is even greater when we consider the elderly population, which responds to vaccination significantly less effectively.

Viruses are responsible for the majority of respiratory infections; among them, human coronaviruses (CoV) are the cause of up to 15% of all respiratory problems. Six human CoV have been described: HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, SARS-CoV, and MERS-CoV. Our laboratory focuses on the design of vaccines and selection of antivirals to protect against human respiratory CoV infections by modulating the innate immune response in the young and elderly populations.

The main aims of our research are:
• To identify CoV genes responsible for virus virulence, to delete or modify them to develop attenuated viruses that are good vaccine candidates, and to determine their effectiveness in animal model systems.
• To identify cell signalling pathways needed for CoV replication, to select antiviral drugs that inhibit these pathways and interfere with virus replication without affecting cell viability. These studies include analysis of the cell phosphorylation networks that affect viral proteins and contribute to virus virulence, to select the corresponding antivirals.
• To determine how CoV influence innate immune responses, to regulate the magnitude and class of response to control CoV-induced pathogenesis. Special attention is provided to the induction of inflammation and to inflammasome activation, as overstimulation of these pathways seems to be responsible for an increase in fatalities during SARS-CoV and MERS-CoV epidemics.
• To study the RNA epigenetic control of innate immune responses to CoV, to promote the expression of small or long non-coding RNAs that favour the innate immune response or counteract the production of RNAs that inhibit this response.

 

 

 

grupoEnjuanesRed

 

Name
Position
Contact
Luis Enjuanes Principal investigator
Isabel Sola Senior scientist
Sonia Zúñiga Postdoctoral scientist
Martina Bécares Predoctoral scientist
Lucía Morales Predoctoral scientist
Carlos Castaño Predoctoral scientist
Alejandro Pascual Predoctoral scientist
Javier Gutiérrez Predoctoral scientist
Javier Cantón Predoctoral scientist
Carlos M. Sánchez Technician
Raúl Fernández Technician
Margarita González Technician

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