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Investigation
Immune Pathogenesis and Viral Reservoir
Research Lines
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Líneas de investigación prioritarias
1. Estudio de los procesos de latencia y reactivación del VIH-1: principales mecanismos homeostáticos responsables de la latencia proviral y la generación de los reservorios virales que imposibilitan la erradicación de la enfermedad.
2. Estudio de dianas terapéuticas para impedir la replicación viral activa durante la infección aguda o primaria y para interferir con la renovación del reservorio viral: análisis de fármacos inhibidores de las kinasas de linfocitos PKC o kinasas de la familia Src como p56Lck.
3. Análisis de los mecanismos de transactivación responsables de la replicación viral activa en linfocitos T CD4+: mecanismos virales implicados en reactivación del provirus.
4. Estudio de mecanismos que impidan la infección y replicación viral eficaz en células del reservorio viral secundario como son los monocitos/macrófagos.
5. Análisis de la resistencia a la infección por VIH-1 en linfocitos T CD4+ aislados de pacientes con distrofia muscular de cintura escapulohumeral/pélvica 1F (LGMD1F), que portan un defecto en el gen de la transportina-3 (tnpo3).
6. Estudio de la sinergia NF-B/Tat para la identificación de nuevas dianas terapéuticas.
7. Estudio de cambios de expresión en el transcriptoma y modificaciones postraduccionales en el proteoma de linfocitos T CD4+ que expresan Tat intracelular y su impacto sobre la estructura del citoesqueleto celular: mecanismo potencial de supervivencia de los reservorios virales.
8. Análisis de los mecanismos de degradación de p65/RelA (NF-B) y su importancia en la infección por VIH-1.
9. Estudio de las modificaciones en el metabolismo del RNA inducidas por la expresión intracelular de Tat y su papel en los mecanismos de supervivencia celular y aumento de la replicación viral.
Otras líneas de investigación
1. Estudio de la respuesta humoral y celular desarrollada en pacientes con Long COVID o COVID persistente.
2. Análisis de biomarcadores predictivos de gravedad en pacientes con distintas presentaciones de COVID-19.
3. Estudio de la respuesta inmune frente a la infección natural por SARS-CoV-2 o por la vacunación frente al COVID-19 desarrollada por pacientes con enfermedades oncohematológicas en estado de inmunodeficiencia.
4. Definición de biomarcadores predictivos de recaída en pacientes con leucemia mieloide crónica que hayan interrumpido el tratamiento con inhibidores de tirosina kinasas.
Publications
Mycobacterium mageritense meningitis in an immunocompetent patient with an intrathecal catheter.
9. Muñoz-Sanz A, Rodríguez Vidigal FF, Vera-Tome A, Jimenez MS. Mycobacterium mageritense meningitis in an immunocompetent patient with an intrathecal catheter. Enfer Infecc Microbiol Clin. 2013; 31:59-6
PUBMED DOIMeasles virus genotype D4 strains with non-standard length M-F non-coding region circulated during the major outbreaks of 2011-2012 in Spain.
2. Gil H, Fernández-García A*, Mosquera MM, Hübschen JM, Castellanos AM, de Ory F, Masa-Calles J, Echevarría JE.Measles virus genotype D4 strains with non-standard length M-F non-coding region circulated during the major outbreaks of 2011-2012 in Spain. PLoS One. 2018 Jul. 16;13(7):e0199975. * Corresponding author.
PUBMED DOIIsolation, antigenicity and immunogenicity of Lleida Bat Lyssavirus
3. Banyard AC, Selden D, Wu G; Thorne L, Jennings D, Marston D, Finke S, Freuling CM, Mueller T, Echevarria JE, Fooks AR. Isolation, antigenicity and immunogenicity of Lleida Bat Lyssavirus. Journal of General Virology, 2018. 99(12):1590-1599
PUBMED DOIShift within age-groups of mumps incidence, hospitalizations and severe complications in a highly vaccinated population
6. López-Perea N, Masa-Callesa J, Torres de Miera MV, Fernández-García A, Echevarría JE, de Ory F, Martínez de Aragón MV. Shift within age-groups of mumps incidence, hospitalizations and severe complications in a highly vaccinated population. Spain, 1998–2014. Vaccine, 2017, 35(34): 4339-4345.
PUBMED DOIThe Complexity of Antibody Responses Elicited against the Respiratory Syncytial Virus Glycoproteins in Hospitalized Children Younger than 2 Years
2. Trento A, Rodriguez-Fernandez R, Gonzalez-Sanchez MI, Gonzalez-Martinez F, Mas V, Vazquez M, et al. The Complexity of Antibody Responses Elicited against the Respiratory Syncytial Virus Glycoproteins in Hospitalized Children Younger than 2 Years. Front Microbiol. 2017;8:2301.
PUBMED DOIPotent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state.
3. Rossey I, Gilman MS, Kabeche SC, Sedeyn K, Wrapp D, Kanekiyo M, et al. Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state. Nat Commun. 2017;8:14158.
PUBMED DOIRapid profiling of RSV antibody repertoires from the memory B cells of naturally infected adult donors
6. Gilman MS, Castellanos CA, Chen M, Ngwuta JO, Goodwin E, Moin SM, et al. Rapid profiling of RSV antibody repertoires from the memory B cells of naturally infected adult donors. Sci Immunol. 2016;1(6).
PUBMED DOICharacterization of a Prefusion-Specific Antibody That Recognizes a Quaternary, Cleavage-Dependent Epitope on the RSV Fusion Glycoprotein.
8. Gilman MS, Moin SM, Mas V, Chen M, Patel NK, Kramer K, et al. Characterization of a Prefusion-Specific Antibody That Recognizes a Quaternary, Cleavage-Dependent Epitope on the RSV Fusion Glycoprotein. PLoS Pathog. 2015;11(7):e1005035.
PUBMED DOIPolyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation.
9. Palomo C, Mas V, Vazquez M, Cano O, Luque D, Terron MC, et al. Polyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation. Virology. 2014;460-461:119-27.
PUBMED DOIBiophysical properties of single rotavirus particles account for the functions of protein shells in a multilayered virus
Jiménez-Zaragoza M., Yubero M.L., Martín-Forero E., Castón J.R., Reguera D., Luque D.*, de Pablo P.J., Rodríguez J.M. 2018. Biophysical properties of single rotavirus particles account for the functions of protein shells in a multilayered virus. eLife 7: e37295. *Corresponding author.
PUBMED DOIAcquisition of functions on the outer capsid surface during evolution of double-stranded RNA fungal viruses
Mata C.P., Luque D., Gómez-Blanco J., Rodríguez J.M., González J.M., Suzuki N., Ghabrial S.A., Carrascosa J.L., Trus B.L., Castón J.R. 2017. Acquisition of functions on the outer capsid surface during evolution of double-stranded RNA fungal viruses. PLoS Pathog. 13(12):e1006755.
PUBMED DOIStructural Insights into the Assembly and Regulation of Distinct Viral Capsid Complexes
Sarker S., C. Terrón M., Khandokar Y., Aragão D., Hardy J.M., Radjainia M., Jiménez-Zaragoza M., de Pablo P.J., Coulibaly F., Luque D., Raidal D.R., Forwood J.K. 2016. Structural Insights into the Assembly and Regulation of Distinct Viral Capsid Complexes. Nat. Commun. 7:13014. IF: 12.124; D1.
PUBMED DOIHeterodimers as the structural unit of the T=1 capsid of the fungal dsRNA Rosellinia necatrix quadrivirus 1
Luque D., Mata C.P., González-Camacho F., González J.M., Gómez-Blanco J., Alfonso C., Rivas G., Havens W.M., Kanematsu S., Suzuki N., Ghabrial S.A., Trus B.L., Castón J.R. 2016. Heterodimers as the structural unit of the T=1 capsid of the fungal dsRNA Rosellinia necatrix quadrivirus 1. J Virol. 90(24):11220-11230. IF: 4.666, Q1.
PUBMED DOISelf-assembly and characterization of small and monodisperse dye nanospheres in a protein cage
Luque D., de la Escosura A., Snijder J., Brasch M., Burnley R.J, Koay M.S.T., Carrascosa J.L., Wuite G.J.L., Roos W.H., Heck A.J.R., J.J.L.M Cornelissen, Torres T., Castón J.R. 2014. Self-assembly and characterization of small and monodisperse dye nanospheres in a protein cage. Chem. Sci.,5, 575-581. IF: 9.211, D1.
DOICryo-EM near-atomic structure of a dsRNA fungal virus shows ancient structural motifs preserved in the dsRNA viral lineage.
Luque D., Gómez-Blanco J., Garriga D., Brilot A.F., González J.M., Havens W.M., Carrascosa J.L., Trus B.L., Verdaguer N., Ghabrial S.A., Castón J.R. 2014. Cryo-EM near-atomic structure of a dsRNA fungal virus shows ancient structural motifs preserved in the dsRNA viral lineage. Proc Natl Acad Sci U S A 111(21):7641-7646. IF: 9.674, D1
PUBMED DOINew insights into rotavirus entry machinery: stabilization of rotavirus spike conformation is independent of trypsin cleavage
Rodríguez J.M., Chichón F.J., Martín-Forero E., González-Camacho F., Carrascosa J.L., Castón J.R., Luque D*. 2014. New insights into rotavirus entry machinery: stabilization of rotavirus spike conformation is independent of trypsin cleavage. PLoS Pathog. 10(5):e1004157. IF: 7.562, D1. * Corresponding autor.
PUBMED DOIAdditional Information
Contact Information
María Teresa Coiras
918223782
mcoiras@isciii.es
generic email: pirv.isciii@gmail.com
Scientific Societies
• Spanis Society for Infectious Diseases and Clinical Microbiology (SEIMC).
• AIDS Study Group (GeSIDA) of SEIMC.
• PIRV is member of the Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC, group CB21/13/00015).
Other links
You can follow the activity of our group in Twitter (X), Instagram and Linkedin.
Collaboration in other projects
Project Title: Rectal microbiota as a factor associated with vulnerability to repeated sexually transmitted infections. Microsex Studio
Principal investigators: Vicente Estrada Pérez (San Carlos Clinical Hospital)
Financing agency: Strategic Action in Health (AES) 2023
Participating entities: San Carlos Clinical Hospital, ISCIII
Duration: 01/01/2024-12/31/2026. Contract/project file: PI23/01545
Project title: Prospective, observational, longitudinal, multicenter study to evaluate clinical efficacy, safety and immunogenicity developed in individuals with Philadelphia-negative Chronic Myeloproliferative Neoplasms treated with JAK inhibitors after receiving full vaccination with Adjuvanted Herpes Zoster Subunit vaccine (Shingrix)
Principal investigators: Valentín García Gutiérrez (Hospital Univ Ramón y Cajal)
Funding agency: GSK Glaxo Smithkline
Participating entities: IRYCIS, ISCIII
Duration: 01/01/2024 – 12/31/2024
Project title: Infection in Solid Organ Transplant recipients: correlation with immune function. Identification of predictive biomarkers and feasibility evaluation with CD45RAneg cell therapy
Principal investigators: Alejandro Luna de Abia, Jesús Fortún (Univ Ramón y Cajal Hospital)
Financing agency: Strategic Health Action (AES) 2023
Participating entities: IRYCIS, ISCIII
Duration: 01/01/2024-12/31/2026
Contract/project file: PI23/01924
Project title: Evaluation of the levels of the System associated with BLyS in patients with post-infectious syndromes and dysautonomic alterations of the heart rhythm
Principal researcher: Pablo Guisado
Funding agency: Spanish Society of Internal Medicine SEMI.
Participating entities: ISCIII, Quironsalud Research Institute for Research and Innovation
Duration 2023-2025
Project title: HIV Open Science (dissemination project)
Principal researcher: Eva Poveda
Financing agency: Spanish Foundation for Science and Technology (FECYT), Call for aid for the Promotion of Scientific, Technological and Innovation Culture.
Participating entities: ISCIII, Fundación Biomédica Galicia Sur, IrsiCaixa, Hospital Vall d’Hebron, Hospital de la Princesa, Fundación Imagina Más, Institute of Biomedicine of Seville (IBIS), Case Western Reserve University (Cleveland, Ohio)
Duration 2023-2024
Contract/project file: 17715
Project title: Identification of immunological biomarkers associated with the cellular and humoral immune response related to vaccination against SARS-CoV-2 in patients with HIV (Annual renewal).
Principal investigator: Rafael Rodríguez Rosado
Funding agency: Alfonso X El Sabio University-Santander Universities. XIII Call for Research Projects.
Participating entities: ISCIII, Severo Ochoa University Hospital
Duration 04/01/2023 – 04/01/2024
Contract/project file: 1,013,006
Project title: Clinical and microbiological impact of the monkeypox virus outbreak in patients in Spain (2022): multicenter project MONKPOX-ESP22, Work package 4, virological research.
Principal researcher: Anabel Negredo (WP4 coordinator); Maria Paz Sánchez Seco (general coordinator)
Financing agency: CIBERINFEC/CIBERESP ISCIII Strategic Action.
Participating entities: ISCIII
Duration July 2022 - May 2023
Contract/project file: MONKPOX-ESP22
Project title: Biomarkers and underlying immunopathological mechanisms of post COVID-19 condition.
Principal investigator: Gemma Moncunill Piñas (IP); Marta Massanella (coIP); María Teresa Coiras López (co-PI)
Financing agency: CIBERINFEC Strategic Action.
Participating entities: ISCIII, IS-Global, IrsiCaixa
Duration 07/28/2022-07/29/2024
Contract/project file: IM22/INF/5
Project title: Identification of immunological biomarkers associated with the cellular and humoral immune response related to vaccination against SARS-CoV-2 in patients with HIV.
Principal investigator: Rafael Rodríguez Rosado
Funding agency: Alfonso X El Sabio University-Santander Universities. XIII Call for Research Projects.
Participating entities: ISCIII, Severo Ochoa University Hospital
Duration 04/01/2022 – 04/01/2023
Contract/project file: 1,013,006
Project title: Characterization of the immune response developed after vaccination with COVID-19 in patients with hematological malignancies.
Principal researcher: Valentín García Gutiérrez
Funding agency: Ministry of Science and Innovation, PI21 - Health research projects (AES 2021). Health research project modality.
Participating entities: ISCIII, Ramón y Cajal University Hospital
Duration 01/01/2022 – 12/31/2024
Contract/project file: PI21_00877
Contact Information
María Teresa Coiras
918223782
mcoiras@isciii.es
generic email: pirv.isciii@gmail.com
Scientific Societies
• Spanis Society for Infectious Diseases and Clinical Microbiology (SEIMC).
• AIDS Study Group (GeSIDA) of SEIMC.
• PIRV is member of the Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC, group CB21/13/00015).
Other links
You can follow the activity of our group in Twitter (X), Instagram and Linkedin.
Collaboration in other projects
Project Title: Rectal microbiota as a factor associated with vulnerability to repeated sexually transmitted infections. Microsex Studio
Principal investigators: Vicente Estrada Pérez (San Carlos Clinical Hospital)
Financing agency: Strategic Action in Health (AES) 2023
Participating entities: San Carlos Clinical Hospital, ISCIII
Duration: 01/01/2024-12/31/2026. Contract/project file: PI23/01545
Project title: Prospective, observational, longitudinal, multicenter study to evaluate clinical efficacy, safety and immunogenicity developed in individuals with Philadelphia-negative Chronic Myeloproliferative Neoplasms treated with JAK inhibitors after receiving full vaccination with Adjuvanted Herpes Zoster Subunit vaccine (Shingrix)
Principal investigators: Valentín García Gutiérrez (Hospital Univ Ramón y Cajal)
Funding agency: GSK Glaxo Smithkline
Participating entities: IRYCIS, ISCIII
Duration: 01/01/2024 – 12/31/2024
Project title: Infection in Solid Organ Transplant recipients: correlation with immune function. Identification of predictive biomarkers and feasibility evaluation with CD45RAneg cell therapy
Principal investigators: Alejandro Luna de Abia, Jesús Fortún (Univ Ramón y Cajal Hospital)
Financing agency: Strategic Health Action (AES) 2023
Participating entities: IRYCIS, ISCIII
Duration: 01/01/2024-12/31/2026
Contract/project file: PI23/01924
Project title: Evaluation of the levels of the System associated with BLyS in patients with post-infectious syndromes and dysautonomic alterations of the heart rhythm
Principal researcher: Pablo Guisado
Funding agency: Spanish Society of Internal Medicine SEMI.
Participating entities: ISCIII, Quironsalud Research Institute for Research and Innovation
Duration 2023-2025
Project title: HIV Open Science (dissemination project)
Principal researcher: Eva Poveda
Financing agency: Spanish Foundation for Science and Technology (FECYT), Call for aid for the Promotion of Scientific, Technological and Innovation Culture.
Participating entities: ISCIII, Fundación Biomédica Galicia Sur, IrsiCaixa, Hospital Vall d’Hebron, Hospital de la Princesa, Fundación Imagina Más, Institute of Biomedicine of Seville (IBIS), Case Western Reserve University (Cleveland, Ohio)
Duration 2023-2024
Contract/project file: 17715
Project title: Identification of immunological biomarkers associated with the cellular and humoral immune response related to vaccination against SARS-CoV-2 in patients with HIV (Annual renewal).
Principal investigator: Rafael Rodríguez Rosado
Funding agency: Alfonso X El Sabio University-Santander Universities. XIII Call for Research Projects.
Participating entities: ISCIII, Severo Ochoa University Hospital
Duration 04/01/2023 – 04/01/2024
Contract/project file: 1,013,006
Project title: Clinical and microbiological impact of the monkeypox virus outbreak in patients in Spain (2022): multicenter project MONKPOX-ESP22, Work package 4, virological research.
Principal researcher: Anabel Negredo (WP4 coordinator); Maria Paz Sánchez Seco (general coordinator)
Financing agency: CIBERINFEC/CIBERESP ISCIII Strategic Action.
Participating entities: ISCIII
Duration July 2022 - May 2023
Contract/project file: MONKPOX-ESP22
Project title: Biomarkers and underlying immunopathological mechanisms of post COVID-19 condition.
Principal investigator: Gemma Moncunill Piñas (IP); Marta Massanella (coIP); María Teresa Coiras López (co-PI)
Financing agency: CIBERINFEC Strategic Action.
Participating entities: ISCIII, IS-Global, IrsiCaixa
Duration 07/28/2022-07/29/2024
Contract/project file: IM22/INF/5
Project title: Identification of immunological biomarkers associated with the cellular and humoral immune response related to vaccination against SARS-CoV-2 in patients with HIV.
Principal investigator: Rafael Rodríguez Rosado
Funding agency: Alfonso X El Sabio University-Santander Universities. XIII Call for Research Projects.
Participating entities: ISCIII, Severo Ochoa University Hospital
Duration 04/01/2022 – 04/01/2023
Contract/project file: 1,013,006
Project title: Characterization of the immune response developed after vaccination with COVID-19 in patients with hematological malignancies.
Principal researcher: Valentín García Gutiérrez
Funding agency: Ministry of Science and Innovation, PI21 - Health research projects (AES 2021). Health research project modality.
Participating entities: ISCIII, Ramón y Cajal University Hospital
Duration 01/01/2022 – 12/31/2024
Contract/project file: PI21_00877