AIDS Immunopathology
Research Lines
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.
Research projects
Content with Investigacion .
- Towards a functional cure: Implications of early antiretroviral therapy and hormonal changes on the HIV reservoir in perinatally infected adolescents. Health Research Fund (FIS) – Carlos III Health Institute (01/01/2026 – 31/12/2028). €72,000. PI: María Pernas, Concepción Casado.
- Determination of factors associated with protection against Human Immunodeficiency Virus type 1 reinfection: Identification of correlates of protection. 9th Gilead Fellowship Program for Biomedical Research, Gilead Sciences, S.L. (01/07/2023 – 30/06/2025). €16,330. PI: María Pernas.
- Impact of the envelope on HIV viral replication: New avenues for vaccine development. Health Research Fund (FIS) – Carlos III Health Institute (01/01/2020 – 31/12/2023). €53,000. PI: María Pernas, Concepción Casado.
- Study of HIV-1 virulence in recently infected patients and its contribution, together with clinical and epidemiological factors, to disease progression. Ministry of Economy and Competitiveness. State Program for Scientific and Technical Research and Innovation (30/12/2016 – 30/06/2021). €145,000. PI: Concepción Casado, Cecilio López-Galíndez.
-Contribution of HIV-1 dual infection to virological and clinical evolution in homo/bisexual men. Health Research Fund (FIS) – Carlos III Health Institute (01/01/2014 – 31/01/2016). €74,410. PI: Cecilio López-Galíndez.
- Characterization of non-pathogenic HIV variants obtained “ex vivo” and “in vitro” for the study of disease pathogenesis. Ministry of Science and Innovation (01/01/2011 – 31/01/2014). €169,400. PI: Cecilio López-Galíndez.
- Spanish AIDS Research Network (RIS-RETIC). Carlos III Health Institute (02/01/2017 – 02/01/2022). €195,212. PI: Cecilio López-Galíndez, Concepción Casado.
Publications
High SARS-CoV-2 viral load and low CCL5 expression levels in the upper respiratory tract are associated with COVID-19 severity.
Pérez-García F, Martin-Vicente M, Rojas-García RL, Castilla-García L, Muñoz-Gomez MJ, Hervás Fernández I, González Ventosa V, Vidal-Alcántara EJ, Cuadros-González J, Bermejo-Martin JF, Resino S#, Martínez I#. High SARS-CoV-2 viral load and low CCL5 expression levels in the upper respiratory tract are associated with COVID-19 severity. J Infect Dis. 2022 Mar 15;225(6):977-982. doi: 10.1093/infdis/jiab604. PMID: 34910814 (A; FI= 7.759; Q1 Microbiology; JCR 2021).
PUBMEDNeighborhood environmental factors linked to hospitalizations of older people for viral lower respiratory tract infections in Spain: a case-crossover study.
Álvaro-Meca A, Sepúlveda-Crespo D#, Resino R, Ryan P, Martínez I#, Resino S#. Neighborhood environmental factors linked to hospitalizations of older people for viral lower respiratory tract infections in Spain: a case-crossover study. Environ Health. 2022 Nov 8;21(1):107. doi: 10.1186/s12940-022-00928-x. PMID: 36348411.
PUBMEDDiagnostic Performance of the HCV Core Antigen Test To Identify Hepatitis C in HIV-Infected Patients: a Systematic Review and Meta-Analysis.
Sepúlveda-Crespo D, Treviño-Nakoura A, Bellon JM, Jiménez-Sousa MA, Ryan P, Martínez I#, Fernández-Rodríguez A#, Resino S#. Diagnostic Performance of the HCV Core Antigen Test To Identify Hepatitis C in HIV-Infected Patients: a Systematic Review and Meta-Analysis. J Clin Microbiol. 2023 Jan 26; 61(1):e0133122. doi: 10.1128/jcm.01331-22. PMID: 36537787.
PUBMEDHCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients.
Brochado-Kith Ó, Martínez I*, Berenguer J, González-García J, Salgüero S, Sepúlveda-Crespo D, Díez C, Hontañón V, Ibañez-Samaniego L, Pérez-Latorre L, Fernández-Rodríguez A, Ángeles Jiménez-Sousa M, Resino S*. HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients. Front Immunol. 2021 Aug 23;12:723196. doi: 10.3389/fimmu.2021.723196. eCollection 2021.PMID: 34497613 (A; FI= 8.786; Q1 Immunology; JCR 2021).
PUBMEDHIV screening and retention in care in people who use drugs in Madrid, Spain: a prospective study
Ryan P, Valencia J, Cuevas G; Troya J; Torres-Macho J; Muñoz-Gómez MJ, Muñoz-Rivas N, Canorea I, Vázquez-Morón S (‡), Resino S (‡ *). HIV screening and retention in care in people who use drugs in Madrid, Spain: A prospective study. Infect Dis Poverty. 2021; 10(1): 111. (A; FI= 10.49; D1, Tropical Medicine; JCR 2021). PMID: 34412695. DOI: 10.1186/s40249-021-00894-5.
PUBMEDObesity-related SNPs and weight gain following first-line antiretroviral therapy.
Berenguer J (*), Jarrín I, Bellón JM, Díez C, Jiménez-Sousa MA, Roca C, González-García J, Dalmau D, Olalla J, Herrero C, Villarroya F, Domingo P, Resino S. Obesity-related SNPs and weight gain following first-line antiretroviral therapy. Clin Inf Dis. 2023; In press. (A; FI= 20.99; D1, Infectious Diseases; JCR 2021).
PUBMED DOIMild profile improvement of immune biomarkers in HIV/HCV-coinfected patients who removed hepatitis C after HCV treatment: a prospective study.
García-Broncano P, Medrano LM, Berenguer J, Brochado O, González-García J, Jiménez-Sousa MA, Quereda C, Sanz J, Téllez MJ, Díaz L, Jiménez JL, Muñoz-Fernández MA, Resino S (*). Mild profile improvement of immune biomarkers in HIV/HCV-coinfected patients who removed hepatitis C after HCV treatment: a prospective study. J Infect 2020; 80(1):99-110. (A; FI= 6.07; Q1, Infectious Diseases; JCR 2020). PMID: 31585189. DOI: 10.1016/j.jinf.2019.09.020.
PUBMEDEvaluation of the possible influence of trailing and paradoxical effects on the clinical outcome of patients with candidemia
Rueda C, Puig-Asensio M, Guinea J, Almirante B, Cuenca-Estrella M, Zaragoza O; CANDIPOP Project from GEIH-GEMICOMED (SEIMC) and REIPI. Evaluation of the possible influence of trailing and paradoxical effects on the clinical outcome of patients with candidemia. Clin Microbiol Infect. 2017 Jan;23(1):49.e1-49.e8.
PUBMED DOIIdentification of Off-Patent Drugs That Show Synergism with Amphotericin B or That Present Antifungal Action against Cryptococcus neoformans and Candida spp
Rossi SA, de Oliveira HC, Agreda-Mellon D, Lucio J, Mendes-Giannini MJS, García-Cambero JP, Zaragoza O. Identification of Off-Patent Drugs That Show Synergism with Amphotericin B or That Present Antifungal Action against Cryptococcus neoformans and Candida spp. Antimicrob Agents Chemother. 2020 Mar 24;64(4):e01921-19. PMCID: PMC7179310.
PUBMED DOIParadoxical Growth of Candida albicans in the Presence of Caspofungin Is Associated with Multiple Cell Wall Rearrangements and Decreased Virulence
Rueda C, Cuenca-Estrella M, Zaragoza O. Paradoxical growth of Candida albicans in the presence of caspofungin is associated with multiple cell wall rearrangements and decreased virulence. Antimicrob Agents Chemother. 2014;58(2):1071-83. PMCID: PMC3910852.
PUBMED DOIHCV cure with direct-acting antivirals improves liver and immunological markers in HIV/HCV-coinfected patients.
Brochado-Kith O, Martínez I, Berenguer J, González-García J, Salgüero S, Sepúlveda-Crespo D, Díez C, Hontañón V, Ibañez-Samaniego L, Pérez-Latorre L, Fernández-Rodríguez A (‡), Jiménez-Sousa MA (‡), Resino S (‡ *). HCV cure with direct-acting antivirals improves liver and immunological markers in HIV/HCV-coinfected patients. Front immunol. 2021; 12:723196. (A; FI= 8.79; Q1, Immunology; JCR 2021). PMID: 34497613. DOI: 10.3389/fimmu.2021.723196.
PUBMEDCryptococcus neoformans induces antimicrobial responses and behaves as a facultative intracellular pathogen in the non mammalian model Galleria mellonella
Trevijano-Contador N, Herrero-Fernández I, García-Barbazán I, Scorzoni L, Rueda C, Rossi SA, García-Rodas R, Zaragoza O. Cryptococcus neoformans induces antimicrobial responses and behaves as a facultative intracellular pathogen in the non mammalian model Galleria mellonella. Virulence. 2015;6(1):66-74. PMCID: PMC4603429.
PUBMED DOIThe formation of titan cells in Cryptococcus neoformans depends on the mouse strain and correlates with induction of Th2-type responses
García-Barbazán I, Trevijano-Contador N, Rueda C, de Andrés B, Pérez-Tavárez R, Herrero-Fernández I, Gaspar ML, Zaragoza O. The formation of titan cells in Cryptococcus neoformans depends on the mouse strain and correlates with induction of Th2-type responses. Cell Microbiol. 2016 Jan;18(1):111-24.
PUBMED DOIPrevalence and undiagnosed fraction of hepatitis C infection in 2018 in Spain: results from a national population-based survey.
• Estirado Gómez A, Justo-Gil S, Limia A, Avellón A, Arce-Arnáez A, González-Rubio R, Diaz A, Del Amo J; Prevalence and undiagnosed fraction of hepatitis C infection in 2018 in Spain: results from a national population-based survey. Sci Rep. 2018 Jan 30;8(1):1858.
PUBMED DOIComparative Analysis of Aspergillus fumigatus Strains: The Reference Genome as a Matter of Concern.
Buitrago MJ, Martín-Gómez T. Timely Diagnosis of Histoplasmosis in Non-endemic Countries: A Laboratory Challenge. Front Microbiol. 2020 Mar 24; 11:467. doi: 10.3389/fmicb.2020.00467. eCollection 2020. PMID: 32269555.
PUBMED DOIIdentification of Novel Short C-Terminal Transcripts of Human SERPINA1 Gene.
Matamala N, Aggarwal N, Iadarola P, Fumagalli M, Gomez-Mariano G, Lara B, Martinez MT, Cuesta I, Stolk J, Janciauskiene S, Martinez-Delgado B. Identification of Novel Short C-Terminal Transcripts of Human SERPINA1 Gene. PLoS One. 2017 Jan 20;12(1):e0170533.
PUBMED DOIA case of respiratory toxigenic diphtheria: Contact tracing results and considerations following a 30-year disease-free interval, Catalonia, Spain, 2015.
Jané, M., Vidal, M.J., Camps, N., Campins, M., Martínez, A., Balcells, J., Martin-Gomez, M.T., Bassets, G., Herrera-Leon, S., Foguet, A., Maresma, M., Follia, N., Uriona, S., Pumarola, T. A case of respiratory toxigenic diphtheria: Contact tracing results and considerations following a 30-year disease-free interval, Catalonia, Spain, 2015. (2018) Eurosurveillance, 23 (13).
PUBMED DOIDevelopment of three multiplex PCR assays targeting the 21 most clinically relevant serogroups associated with Shiga toxin-producing E. coli infection in humans
Sánchez, S., Llorente, M.T., Echeita, M.A., Herrera-León, S. Development of three multiplex PCR assays targeting the 21 most clinically relevant serogroups associated with Shiga toxin-producing E. coli infection in humans (2015) PLoS ONE, 10 (1).
PUBMED DOIShiga toxin-producing Escherichia coli and atypical enteropathogenic E. coli infection in a Spanish household
Sánchez, S., Cenoz, M.G., Martín, C., Beristain, X., Llorente, M.T., Herrera-León, S. Cluster investigation of mixed O76:H19 Shiga toxin-producing Escherichia coli and atypical enteropathogenic E. coli infection in a Spanish household (2014) Epidemiology and Infection, 142 (5), pp. 1029-1033.
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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María Pernas Escario
Senior Specialized Technician of Public Research Organizations (OPIs)
ORCID code: 0000-0003-2966-0160
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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
List of staff
Additional Information
The AIDS Immunopathology Unit has been coordinated since 2000 by Dr. José Alcamí, bringing together during its history more than 20 independent researchers who collaboratively study different aspects of HIV infection. During this years, more than 30 visiting researchers and more than 50 national and international students have passed through the unit. From the beginning of the year 2025, Javier García Pérez and Francisco Díez Fuertes assumed the coordination of the AIDS Immunopathology Unit, with the aim of projecting its scientific competitiveness following multidisciplinary approaches and through the maintenance of the current close collaborations, as well as the promotion of participation in new national and international research networks.
Historically, the current members of the unit have focused on different lines of basic research that include the study of antibodies and the development of vaccines against HIV-1, the study of viral entry and tropism of the virus or the study of the host through the genomic characterization of populations with an extreme phenotype. Currently, the activity of our unit in the field of HIV-1 is focused on three main lines:
1. Mecanismos moleculares asociados a la protección de la infección por VIH-1 en pacientes con distrofia muscular de cinturas dominante D2 (LGMDD2).
2. Generación de anticuerpos neutralizantes de uso terapéutico basados en la respuesta neutralizante de amplio espectro frente a virus fundadores.
3. Cribado y caracterización de nuevos fármacos anti-latencia frente al VIH-1.
A partir del año 2020, nuestra unidad se vuelca con la investigación sobre COVID-19, participando y liderando diferentes proyectos de investigación aplicada y clínica. Fruto de esta fuerte implicación en el campo, en la actualidad se mantienen diferentes estudios sobre la caracterización de la respuesta inmune frente a SARS-CoV-2, integrando diferentes técnicas de virología molecular, estrategias de inteligencia epidemiológica y tecnologías de célula única.
We also participate in different research consortiums and networks, such as the Spanish AIDS Research Network or the Center for Biomedical Research in Infectious Diseases Network (CIBER-INFEC), in which we participate as researchers in different lines and work packages within the research programs “Global Health, emerging and re-emerging infections” as well as “HIV/AIDS and sexually transmitted infections”.
Supervised doctoral theses
1. GENOMIC AND FUNCTIONAL ANALYSIS OF HIV-1 PROTECTION PARAMETERS IN PATIENTS WITH SLOW PROGRESSION OF INFECTION.
Student: Erick de la Torre Tarazona.
Supervisors: José Alcamí and Francisco Díez Fuertes.
Academic entity: Universidad Autónoma de Madrid.
Defense date: July 14th, 2020.
2. ANALYSIS OF MIARN EXPRESSION PROFILES AND FUNCTIONAL CHARACTERIZATION IN HIV-POSITIVE INDIVIDUALS WITH DIFFERENT PROGRESSION TO AIDS.
Student: Rubén Ayala Suárez.
Supervisors: José Alcamí and Francisco Díez Fuertes.
Academic entity: Universidad de Alcalá.
Defense date: June 12nd, 2023.
The AIDS Immunopathology Unit has been coordinated since 2000 by Dr. José Alcamí, bringing together during its history more than 20 independent researchers who collaboratively study different aspects of HIV infection. During this years, more than 30 visiting researchers and more than 50 national and international students have passed through the unit. From the beginning of the year 2025, Javier García Pérez and Francisco Díez Fuertes assumed the coordination of the AIDS Immunopathology Unit, with the aim of projecting its scientific competitiveness following multidisciplinary approaches and through the maintenance of the current close collaborations, as well as the promotion of participation in new national and international research networks.
Historically, the current members of the unit have focused on different lines of basic research that include the study of antibodies and the development of vaccines against HIV-1, the study of viral entry and tropism of the virus or the study of the host through the genomic characterization of populations with an extreme phenotype. Currently, the activity of our unit in the field of HIV-1 is focused on three main lines:
1. Mecanismos moleculares asociados a la protección de la infección por VIH-1 en pacientes con distrofia muscular de cinturas dominante D2 (LGMDD2).
2. Generación de anticuerpos neutralizantes de uso terapéutico basados en la respuesta neutralizante de amplio espectro frente a virus fundadores.
3. Cribado y caracterización de nuevos fármacos anti-latencia frente al VIH-1.
A partir del año 2020, nuestra unidad se vuelca con la investigación sobre COVID-19, participando y liderando diferentes proyectos de investigación aplicada y clínica. Fruto de esta fuerte implicación en el campo, en la actualidad se mantienen diferentes estudios sobre la caracterización de la respuesta inmune frente a SARS-CoV-2, integrando diferentes técnicas de virología molecular, estrategias de inteligencia epidemiológica y tecnologías de célula única.
We also participate in different research consortiums and networks, such as the Spanish AIDS Research Network or the Center for Biomedical Research in Infectious Diseases Network (CIBER-INFEC), in which we participate as researchers in different lines and work packages within the research programs “Global Health, emerging and re-emerging infections” as well as “HIV/AIDS and sexually transmitted infections”.
Supervised doctoral theses
1. GENOMIC AND FUNCTIONAL ANALYSIS OF HIV-1 PROTECTION PARAMETERS IN PATIENTS WITH SLOW PROGRESSION OF INFECTION.
Student: Erick de la Torre Tarazona.
Supervisors: José Alcamí and Francisco Díez Fuertes.
Academic entity: Universidad Autónoma de Madrid.
Defense date: July 14th, 2020.
2. ANALYSIS OF MIARN EXPRESSION PROFILES AND FUNCTIONAL CHARACTERIZATION IN HIV-POSITIVE INDIVIDUALS WITH DIFFERENT PROGRESSION TO AIDS.
Student: Rubén Ayala Suárez.
Supervisors: José Alcamí and Francisco Díez Fuertes.
Academic entity: Universidad de Alcalá.
Defense date: June 12nd, 2023.