Cellular Immunology
Líneas de investigación
Content with Investigacion .
Research
The Molecular Virology group focuses its research on the study of HIV-1 genetic variation and viral evolution using both in vitro and ex vivo approaches, structured around the following research lines:
- Non-progressor patients. These patients maintain control of the disease in the absence of antiretroviral therapy and have therefore been proposed as a model of functional cure. Our objective is to study the contribution of viral factors to disease control through biological characterization and analysis of viral evolution in individuals with undetectable viral loads (elite controllers, EC), compared with individuals showing other patterns of viral control.
- Viral envelope. This viral protein is key in determining viral fitness. Therefore, its functionality significantly affects infection progression. In collaboration with Dr. Blanco and Dr. Valenzuela, we study which specific events (CD4 binding, fusogenicity, etc.) are associated with envelope functionality. To this end, we have analyzed envelopes from individuals with different patterns of disease progression. Some of these have been contributed to the AIDS Research Network envelope biobank for broader use.
- Dual infection. Infection with more than one viral variant (either through co-infection or superinfection) may have consequences for infection pathogenesis. Within our group, different aspects of DI have been analyzed, including its detection in non-progressor patients, its prevalence and incidence in Spain, and its influence on the neutralizing antibody response.
- Molecular Epidemiology. The group has analyzed viral evolution throughout the epidemic in Spain and in other countries (the Netherlands, Italy, Germany, Uruguay, Panama, Brazil, etc.).
- Role of amino acid residues in reverse transcriptase. We study the role of specific amino acid residues in HIV-1 reverse transcriptase in enzymatic function and replication capacity using an infectious molecular clone previously obtained by the group.
- “In vitro” variability. Serial passage studies have been used to detect the mechanisms responsible for the gain or loss of viral fitness.
- Antiviral studies. We have analyzed the selection of resistance mutations in vitro against different antivirals, as well as the effect of these mutations on viral fitness, and the activity of new antivirals such as ATR inhibitors.
Virological Diagnosis and Reference in HIV and HTLV Infections
The research group provides diagnostic and reference activities through the service portfolio of the National Center for Microbiology to the entire Spanish National Health System.
These services include:
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Diagnosis and reference of HIV infection (types 1 and 2) through detection of specific antibodies and detection of proviral DNA by PCR.
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Diagnosis and reference of HTLV-I/II infection through detection of specific antibodies and detection of proviral DNA by PCR. Quantification of HTLV-1 proviral load by real-time PCR.
European Union Reference Laboratory (EURL) in the field of in vitro diagnostic medical devices for microbiological diagnosis (IVD) of HIV and HTLV (Regulation 2023/2713 of December 5th, 2023). Our role is to confirm the reliability and effectiveness of devices for detecting these pathogens and to ensure their specific performance requirements through laboratory testing before they can be marketed within the European Union.
Publicaciones destacadas
Where are we with monoclonal antibodies for multidrug-resistant infections?
Where are we with monoclonal antibodies for multidrug-resistant infections? McConnell MJ. Drug Discov Today. 2019 May;24(5):1132-1138. doi: 10.1016/j.drudis.2019.03.002.
PUBMEDPeptidoglycan recycling contributes to intrinsic resistance to fosfomycin in Acinetobacter baumannii
Peptidoglycan recycling contributes to intrinsic resistance to fosfomycin in Acinetobacter baumannii. Gil-Marqués ML, Moreno-Martínez P, Costas C, Pachón J, Blázquez J, McConnell MJ. J Antimicrob Chemother. 2018 Nov 1;73(11):2960-2968. doi: 10.1093/jac/dky289.
PUBMEDImmunization with lipopolysaccharide-free outer membrane complexes protects against Acinetobacter baumannii infection
Immunization with lipopolysaccharide-free outer membrane complexes protects against Acinetobacter baumannii infection. Pulido MR, García-Quintanilla M, Pachón J, McConnell MJ. Vaccine. 2018 Jul 5;36(29):4153-4156. doi: 10.1016/j.vaccine.2018.05.113.
PUBMEDPhenotypic changes associated with Colistin resistance due to Lipopolysaccharide loss in Acinetobacter baumannii
Phenotypic changes associated with Colistin resistance due to Lipopolysaccharide loss in Acinetobacter baumannii. Carretero-Ledesma M, García-Quintanilla M, Martín-Peña R, Pulido MR, Pachón J, McConnell MJ. Virulence. 2018 Dec 31;9(1):930-942. doi: 10.1080/21505594.2018.1460187.
PUBMEDCurso de Gestión de Calidad y Buenas Prácticas de Laboratorio. Ed. 3
Grammatico JP, Cuevas L (Edits.) y Grupo de expertos de la Organización Panamericana de la Salud OPS/OMS. Curso de Gestión de Calidad y Buenas Prácticas de Laboratorio. Ed. 3. OPS/OMS;. Washington, D.C., 2016. Disponible en: “http://iris.paho.org/xmlui/handle/123456789/31168”. ISBN: 978-92-75-11906-8
Gestión de la Calidad para laboratorios de ensayo. 1ª ed.
Grammatico JP, Cuevas L (Edits.). Gestión de la Calidad para laboratorios de ensayo. 1ª ed. Conicet-Madri+d; Buenos Aires, 2011. Disponible en: “http://www.madrimasd.org/Laboratorios/Documentos/Red-Laboratorios/documentos/Gest_Calidad_Ensayo.pdf”. ISBN: 978-950-692-095-1
Curso de Gestión de Calidad y Buenas Prácticas de Laboratorio.
Grupo de expertos de la Organización Panamericana de la Salud OPS/OMS. Curso de Gestión de Calidad y Buenas Prácticas de Laboratorio. OPS; Documentos Técnicos THR/HT 2009/001. Washington, D.C., 2009. ISBN: 978-92-75-32977-1
Guía Latinoamericana para la implementación de Código de Ética en los laboratorios de salud.
Grupo de expertos de la Organización Panamericana de la Salud (OPS/OMS). Guía Latinoamericana para la implementación de Código de Ética en los laboratorios de salud. Organización Panamericana de la Salud. Documentos Técnicos. Políticas y Regulación. THS/EV-2007/001; 2007. ISBN: 92-7-532702-5
Identification of HIV-1 circulating BF1 recombinant form (CRF75_BF1) of Brazilian origin that also circulates in Southwestern Europe
Bacqué J, Delgado E, Gil H, Ibarra S, Benito S, García-Arata I, Moreno-Lorenzo M, Sáez de Arana E, Gómez-González C, Sánchez M, Montero V and Thomson MM. Front Microbiol. 2023. 14: 1301374
PUBMED DOIFactors associated with HIV-1 resistance to integrase strand transfer inhibitors in Spain: Implications for dolutegravir-containing regimens.
Gil H, Delgado E, Benito S, Moreno-Lorenzo M, Thomson MM and Spanish Group for the study of antirretroviral drug Resistance. Front Microbiol. 2022. 13:1051096
PUBMED DOITransmission clusters, predominantly associated with men who have sex with men, play a main role in the propagation of HIV-1 in Northern Spain (2013-2018).
Gil H, Delgado E, Benito S, Georgalis L, Montero V, Sánchez M, Cañada-García JE, García-Bodas E, Diaz A, Thomson MM and Spanish group of the study of new HIV diagnoses. Front Microbiol. 2022. 13:782609
PUBMED DOIHigh-Resolution Melting Assay to Detect the Mutations That Cause the Y132F and G458S Substitutions at the ERG11 Gene Involved in Azole Resistance in Candida parapsilosis
Nuria Trevijano-Contador, Elena López-Peralta, Jorge López-López, Alejandra Roldán, Cristina de Armentia, Óscar Zaragoza. Mycoses 2024 Nov;67(11):e13811
PUBMED DOIBroad Protection against Invasive Fungal Disease from a Nanobody Targeting the Active Site of Fungal β-1,3-Glucanosyltransferases
Redrado-Hernández S, Macías-León J, Castro-López J, Belén Sanz A, Dolader E, Arias M, González-Ramírez AM, Sánchez-Navarro D, Petryk Y, Farkaš V, Vincke C, Muyldermans S, García-Barbazán I, Del Agua C, Zaragoza O, Arroyo J, Pardo J, Gálvez EM, Hurtado-Guerrero R. Angew Chem Int Ed Engl. 2024 Aug 19;63(34):e202405823.
PUBMED DOIDiagnósitico microbiológico y control de la legionelosis
Pelaz Antolín, C., et al., En Procedimientos en Microbiología Clínica, E.C.y.R. Cantón, Editor. 2005, SEIMC. p. 1-72.
PUBMEDLegionella-Biofilms-Amebas, un problema industrial, de sanidad ambiental y de salud pública
Juana María González-Rubio, Celia Játiva, Almudena Cascajero, Fernando González-Camacho. Infoplagas, nº 112, agosto 2023 pags: 20-24. (Artículo de divulgación).
DOIPrograma de Legionelosis. En Echevarría Mayo JE y Oteo Iglesias J (Editores). Programas de Vigilancia Microbiológica pags: 74-80. Centro Nacional de Microbiología, Madrid: Instituto de Salud Carlos III, 2021.
Bellido B y Pelaez C: Programa de Legionelosis. En Echevarría Mayo JE y Oteo Iglesias J (Editores). Programas de Vigilancia Microbiológica pags: 74-80. Centro Nacional de Microbiología, Madrid: Instituto de Salud Carlos III, 2021.
Content with Investigacion .
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Concepción Casado Herrero
Tenure Scientist of Public Research Organizations (OPIs)
ORCID code: 0000-0003-3412-2877
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Virginia Sandonís Martín
Senior Specialized Technician of Public Research Organizations (OPIs)
ORCID code: 0000-0001-5762-7531
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Rosa Fuentes Fernández
Laboratory Technician
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María Pernas Escario
Senior Specialized Technician of Public Research Organizations (OPIs)
ORCID code: 0000-0003-2966-0160
List of staff
Información adicional
Our current objective is the analysis of costimulatory molecules that modulate lymphocyte activation and the adaptive and innate immune response; specifically the inducible costimulator ICOS and its association with the enzyme phosphatidylinositol-3-kinase (PI3K). ICOS is induced in T lymphocytes and some innate immune cells; It is involved in normal and pathological immune responses and in inflammation regulatory circuits. Its signals are mediated by the association of PI3K, enzymes that regulate many aspects of the response to antigen, lymphoproliferative syndromes, lupus and cancer.
We analyzed the usefulness of ICOS, its ligand (ICOS-L) and the PI3K associated with ICOS as therapeutic targets in immune response to infections and tumors and in autoimmune diseases. We used two different approaches: i) pharmacological (effect of PI3K p110 isoform inhibitors on immune response) and ii) genetic (analysis of mouse models with tissue-specific conditioned modification of PI3K p110α). We study; 1) The role of PI3K-p110α in the activation and differentiation of cells involved in innate and adaptive immune response to infection, tumors and autoimmunity, seeking new therapies. 2) The functional consequences of costimulation by ICOS/ICOS-L and its mediators, in innate immune cells that simultaneously express ICOS and its ligand.