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
Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients.
12. Martin-Vicente M#, Almansa R#, Martínez I#, Tedim AP, Bustamante E, Tamayo L, Aldecoa C, Gómez JM, Renedo G, Berezo JÁ, Cedeño JA, Mamolar N, García Olivares P, Herrán-Monge R, Cicuendez R, Enríquez P, Ortega A, Jorge N, Doncel C, de la Fuente A, Bustamante-Munguira J, Muñoz-Gómez MJ, González-Rivera M, Puertas C, Más V, Vázquez M, Pérez-García F, Rico-Feijoo J, Martín S, Motos A, Fernandez-Barat L, Eiros JM, Dominguez-Gil M, Ferrer R, Barbé F, Trapiello W, Kelvin DJ, Bermejo-Martin JF, Resino S, Torres A. Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients. J Intern Med. 2022 Feb; 291(2):232-240. doi: 10.1111/joim.13386. PMID: 34611927 (A; FI= 13.068; D1 Medicine, General & Internal; JCR 2021).
PUBMEDStrategies Targeting the Innate Immune Response for the Treatment of Hepatitis C Virus-Associated Liver Fibrosis.
13. Sepulveda-Crespo D, Resino S*, Martinez I*. Strategies Targeting the Innate Immune Response for the Treatment of Hepatitis C Virus-Associated Liver Fibrosis. Drugs. 2021 Drugs. 2021 Mar; 81(4):419-443. doi: 10.1007/s40265-020-01458-x. PMID: 33400242. (R; FI= 11.431; D1 Pharmacology & Pharmacy; JCR 2021).
PUBMEDMetabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation FRONTIERS IN IMMUNOLOGY.
3 Ceballos, Francisco C.; Virseda-Berdices, Ana; Resino, Salvador; et al; Jimenez-Sousa, Maria Angeles. (19/19). 2022. Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation FRONTIERS IN IMMUNOLOGY. ISSN 1664-3224.
Metabolomic changes after DAAs therapy are related to the improvement of cirrhosis and inflammation in HIV/HCV-coinfected patients.
4 Virseda-Berdices, Ana; Rojo, David; Martinez, Isidoro; et al; Jimenez-Sousa, Maria Angeles. (14/14). 2022. Metabolomic changes after DAAs therapy are related to the improvement of cirrhosis and inflammation in HIV/HCV-coinfected patients. BIOMEDICINE & PHARMACOTHERAPY. 147:112623. ISSN 1950-6007.
HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients FRONTIERS IN IMMUNOLOGY.
7 Brochado-Kith, Oscar; Martinez, Isidoro; Berenguer, Juan; et al; Jiménez-Sousa, Maria Angeles (‡, AC); Resino, Salvador (‡, AC). (13/13). 2021. HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients FRONTIERS IN IMMUNOLOGY. 12:723196. ISSN 1664-3224.
Plasma miRNA profile at COVID-19 onset predicts severity status and mortality
3. Fernández-Pato A; Virseda-Berdices A; Resino S; et al; Fernández-Rodríguez A (AC). (20/20). 2022. Plasma miRNA profile at COVID-19 onset predicts severity status and mortality Emerging Microbes and Infections. Taylor & Francis Online. ISSN 2222-1751.
DOIDiagnostic Performance of the HCV Core Antigen Test To Identify Hepatitis C in HIV-Infected Patients: a Systematic Review and Meta-Analysis
4. Sepúlveda-Crespo D; Treviño-Nakoura A; Bellon JM; Jiménez-Sousa MA; Ryan P; Martínez I; Fernández-Rodríguez A (AC); Resino S. (7/8). 2022. Diagnostic Performance of the HCV Core Antigen Test To Identify Hepatitis C in HIV-Infected Patients: a Systematic Review and Meta-Analysis.Journal of clinical microbiology. pp.e0133122. ISSN 0095-1137.
DOIMetabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation
6. Ceballos FC; Virseda-Berdices A; Resino S; et al; Jiménez-Sousa MÁ (AC). (19/19). 2022. Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation.Frontiers in immunology. 13, pp.925558. WOS (78)
DOINovel genes and sex differences in COVID-19 severity
7. Cruz R; Almeida SD; Heredia ML; et al; Fernández-Rodríguez A; Carracedo Á. (51/168). 2022. Novel genes and sex differences in COVID-19 severity. Human molecular genetics. ISSN 0964-6906.
DOIDifferent HCV Exposure Drives Specific miRNA Profile in PBMCs of HIV Patients
8. Valle-Millares D; Brochado-Kith O; Martín-Carbonero L; et al; Fernández-Rodríguez A (AC). (22/22). 2021. Different HCV exposure drives specific miRNA profile in PBMCs of HIV patients Biomedicines. MDPI. 9-11, pp.1627.
DOIAre Reduced Levels of Coagulation Proteins Upon Admission Linked to COVID-19 Severity and Mortality?
9. Ceballos F; Ryan P; Blancas R; et al; Fernández-Rodríguez A (AC); Jiménez-Sousa MA. (19/20). 2021. Are Reduced Levels of Coagulation Proteins Upon Admission Linked to COVID-19 Severity and Mortality? Frontiers in Medicine. Frontiers. 8-718053.
DOITelomere Length Increase in HIV/HCV-Coinfected Patients with Cirrhosis after HCV Eradication with Direct-Acting Antivirals
12 . Molina-Carrión S; Brochado-Kith, Oscar; González-García J; et al; Angeles Jimenez-Sousa, Maria. (16/16). 2020. Telomere length increase in HIV/HCV-coinfected patients with cirrhosis after HCV eradication with direct acting antivirals. JOURNAL OF CLINICAL MEDICINE. MDPI. ISSN 2077-0383.
DOIMicroRNA Profile of HCV Spontaneous Clarified Individuals, Denotes Previous HCV Infection
15. Brochado-Kith, Oscar; Gomez-Sanz, Alicia; Real LM; et al; Fernandez-Rodriguez, Amanda (AC). (16/16). 2019. MicroRNA Profile of HCV Spontaneous Clarified Individuals, Denotes Previous HCV Infection JOURNAL OF CLINICAL MEDICINE. MDPI. 7. ISSN 2077-0383.
DOIPersistent Immunity against SARS-CoV-2 in Individuals with Oncohematological Diseases Who Underwent Autologous or Allogeneic Stem Cell Transplantation after Vaccination
Persistent Immunity against SARS-CoV-2 in Individuals with Oncohematological Diseases Who Underwent Autologous or Allogeneic Stem Cell Transplantation after Vaccination. Rodríguez-Mora S, Pérez-Lamas L, Solera Sainero M, Torres M, Sánchez-Menéndez C, Corona M, Mateos E, Casado-Fernández G, Alcamí J, García-Pérez J, Pérez-Olmeda M, Murciano-Antón A, López-Jiménez J, García-Gutiérrez V, Coiras M (AC). Cancers 2023, 15(8), 2344. doi: 10.3390/cancers15082344. PMID: 37190272.
PUBMED DOISustained Cytotoxic Response of Peripheral Blood Mononuclear Cells from Unvaccinated Individuals Admitted to the ICU Due to Critical COVID-19 Is Essential to Avoid a Fatal Outcome
Sustained Cytotoxic Response of Peripheral Blood Mononuclear Cells from Unvaccinated Individuals Admitted to the ICU Due to Critical COVID-19 Is Essential to Avoid a Fatal Outcome. Casado-Fernández G, Corona M, Torres M, Saez AJ, Ramos-Martín F, Manzanares M, Vigón L, Mateos E, Pozo F, Casas I, García-Gutierrez V, Rodríguez-Mora S, Coiras M (AC). Int J Environ Res Public Health. 2023 Jan20;20(3):1947. doi: 10.3390/ijerph20031947. PMID: 36767310.
PUBMED DOIDasatinib: effects on the macrophage phospho proteome with a focus on SAMHD1 and HIV-1 infection
Dasatinib: effects on the macrophage phospho proteome with a focus on SAMHD1 and HIV-1 infection. Williams ESCP, Szaniawski MA, Martins LJ, Innis EA, Alcamí J, Hanley TM, Spivak AM, Coiras M, Planelles V. Clin Res HIV AIDS.2022;8(1):1053. https://pubmed.ncbi.nlm.nih.gov/36589263/. PMID: 36589263.
PUBMEDEarly Cellular and Humoral Responses Developed in Oncohematological Patients after Vaccination with One Dose against COVID-19
Early Cellular and Humoral Responses Developed in Oncohematological Patients after Vaccination with One Dose against COVID-19. Rodríguez-Mora S, Corona M, Torres M, Casado-Fernández G, García-Pérez J, Ramos-Martín F, Vigón L, Manzanares M, Mateos E, Martín-Moro F, Zurdo-Castronuño A, Murciano-Antón MA, Alcamí J, Pérez-Olmeda M, López-Jiménez J, García-Gutiérrez V, Coiras M (AC). J Clin Med. 2022 May 16;11(10):2803. doi: 10.3390/jcm11102803. PMID: 35628927.
PUBMED DOIChanges in the immune response against SARS-CoV-2 in individuals with severe COVID-19 treated with high dose of vitamin D
Changes in the immune response against SARS-CoV-2 in individuals with severe COVID-19 treated with high dose of vitamin D. Torres M, Casado G, Vigón L, Rodríguez-Mora S, Mateos E, Ramos-Martín F, López-Wolf D, Sanz-Moreno J, Ryan-Murua P, Taboada-Martínez ML, López-Huertas MR, Cervero M, Coiras M (AC). Biomed Pharmacother. 2022 Apr 14;150:112965. doi: 10.1016/j.biopha.2022.112965. PMID: 35468580.
PUBMED DOIStrong Cellular Immune Response, but Not Humoral, against SARS-CoV-2 in Oncohematological Patients with Autologous Stem Cell Transplantation after Natural Infection.
Strong Cellular Immune Response, but Not Humoral, against SARS-CoV-2 in Oncohematological Patients with Autologous Stem Cell Transplantation after Natural Infection. Vigón L, Sánchez-Tornero A, Rodríguez-Mora S, García-Pérez J, Corona de Lapuerta M, Pérez-Lamas L, Casado-Fernández G, Moreno G, Torres M, Mateos E, Murciano-Antón MA, Alcamí J, Pérez-Olmeda M, López-Jiménez J, García-Gutiérrez V, Coiras M (AC). J Clin Med. 2022 Apr 11;11(8):2137. doi: 10.3390/jcm11082137. PMID: 35456230.
PUBMED DOIPersistent overactive cytotoxic immune response in a Spanish cohort of individuals with Long-COVID: Identification of diagnostic biomarkers
Persistent overactive cytotoxic immune response in a Spanish cohort of individuals with Long-COVID: Identification of diagnostic biomarkers. Galán M, Vigón L, Fuertes D, Murciano-Antón MA, Casado-Fernández G, Domínguez-Mateos S, Mateos E, Ramos-Martín F, Planelles V, Torres M, Rodríguez-Mora S, López-Huertas MR, Coiras M (CA). Front Immunol. 2022 Mar 25;13:848886. doi: 10.3389/fimmu.2022.848886. PMID: 35401523
PUBMED DOIContent 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.