Luis Enjuanes
Group Leader
Isabel Sola
Group Leader
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
Morales L, Oliveros JC, Fernandez-Delgado R, tenOever BR, Enjuanes L, Sola I. SARS-CoV-Encoded Small RNAs Contribute to Infection-Associated Lung Pathology. Cell Host Microbe. 2017;21(3):344-355
Enjuanes L, Zuniga S, Castano-Rodriguez C, Gutierrez-Alvarez J, Canton J, Sola I. Molecular basis of coronavirus virulence and vaccine development. Adv Virus Res 2016; 96: 245-286
Regla-Nava JA, Nieto-Torres JL, Jimenez-Guardeno JM, Fernandez-Delgado R, Fett C, Castano-Rodriguez C, Perlman S, Enjuanes L, DeDiego ML. SARS coronaviruses with mutations in E protein are attenuated and promising vaccine candidates. J Virol 2015; 89: 3870-3887
Sola I, Almazán F, Zúñiga S, Enjuanes L. Continuous and discontinuous RNA synthesis in coronaviruses. Annu Rev Virol 2015; 2: 265-288
Jimenez-Guardeno JM, Regla-Nava JA, Nieto-Torres JL, DeDiego ML, Castano-Rodriguez C, Fernandez-Delgado R, Perlman S, Enjuanes L. Identification of the mechanisms causing reversion to virulence in an attenuated SARS-CoV for the design of a genetically stable vaccine. PLoS Pathog 2015; 11: e1005215
Human 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.
