AIDS Immunopathology
Research Lines
Content with Investigacion .
Susceptibilidad del huésped a las infecciones fúngicas invasoras
Se estima que más de un millón y medio de personas mueren al año en el mundo debido a una enfermedad fúngica invasora (EFI). Los tratamientos con inmunosupresores, terapias con corticoides, trasplantes de células hematopoyéticas y órgano sólido así como tratamientos quimioterapéuticos contra el cáncer han favorecido el aumento de estas infecciones fúngicas. El género Aspergillus es la principal causa de EFI por hongos filamentosos, siendo A. fumigatus la especie principalmente aislada en la mayoría de los casos y más frecuentemente asociada a Aspergilosis Invasora.
Muchas de estas infecciones están infra-diagnosticadas debido, tanto a la falta de sospecha clínica como a las limitaciones diagnósticas. Esta línea de investigación tiene como principal objetivo mejorar el pronóstico de la infecciones en pacientes con riesgo de desarrollar infecciones invasoras por hongos. Para ello se estudian marcadores del individuo (denominados biomarcadores del hospedador) que puedan ser detectados de forme temprana en muestras de pacientes en riesgo y que nos permita estratificar a los mismos en función de la susceptibilidad a desarrollar una infección invasora por hongos. Además, estudios realizados en los últimos años muestran que el fondo genético del hospedador está asociado con la predisposición al desarrollo de este tipo de enfermedades. En concreto se han identificado polimorfismos genéticos de nucleótido simple (“Single Nucleotide Polymorphism”- SNP) en genes que codifican para componentes celulares que interaccionan con estructuras fúngicas y/o que están involucradas en la respuesta inmune del huésped frente a agentes infecciosos como Aspergillus. En este sentido se han estandarizado y aplicado herramientas para la detección de SNPs en humanos de genes diana asociados concretamente con la susceptibilidad a la Aspergilosis Invasora.
Estudio de los mecanismos de virulencia en Aspergillus fumigatus
En paralelo al estudio de la respuesta del hospedador se sigue una línea cuyo objetivo es caracterizar mecanismos de virulencia en A. fumigatus. Uno de los principales mecanismos por los que A. fumigatus es capaz de causar enfermedad en humanos es su capacidad de adaptarse a las condiciones ambientales del hospedador. Entre las moléculas y los genes que se han relacionado con la virulencia de este hongo se encuentran componentes de la pared celular, genes y moléculas relacionadas con la evasión de la respuesta inmune, sistemas de detoxificación de los compuestos derivados del oxígeno, la producción de toxinas, la obtención de nutrientes como hierro, fósforo, nitrógeno y la adaptación a pH y temperatura del hospedador. Estos estudios permiten profundizar en el conocimiento sobre la patogenicidad de este hongo e identificar nuevas dianas terapéuticas
Publications
Off-label use of maraviroc in HIV-1-infected paediatric patients in clinical practice.
Palladino C, Navarro Gomez ML, Soler-Palacin P, Gonzalez-Tome MI, Jiménez de Ory S, Espiau M, Pérez-Hoyos S, León-Leal JA, Méndez M, Moreno-Pérez D, Fortuny C, uer A, Pocheville I, Moreno S, Briz V, on behalf of the CoRISpe Working Group. Off-label use of maraviroc in HIV-1-infected paediatric patients in clinical practice. AIDS 2015; 29-16, pp.2155-2159. (A; FI= 4,407; Q1 Infectious Disease).
PUBMED DOIComparative sensitivity of commercial tests for hepatitis E genotype 3 virus antibody detection.
Comparative sensitivity of commercial tests for hepatitis E genotype 3 virus antibody detection. Avellon A, Morago L, Garcia-Galera del Carmen M, Munoz M, Echevarría JM. J Med Virol. 2015 Nov;87(11):1934-9. Epub 2015 May 29.
PUBMED DOIRelative telomere length impact on mortality of COVID-19: sex differences.
Virseda-Berdices A, Concostrina-Martinez L, Martínez-González O, Blancas R, Resino S, Ryan P, De Juan C, Moreira-Escriche P, Martin-Vicente M, Brochado-Kith O, Blanca-López N, Jiménez-Sousa MA (‡,*), Fernández-Rodríguez A (‡). Relative telomere length impact on mortality of COVID-19: sex differences. J Med Virol 2023; 98 (1): e28368 (A; FI= 20.96; D1, Virology; JCR 2021).
PUBMEDActivity of host antimicrobials against multidrug resistant Acinetobacter baumannii acquiring colistin resistance through loss of lipopolysaccharide
García-Quintanilla, M., Pulido, M. R., Moreno-Martínez, P., Martín-Peña, R., López-Rojas, R., Pachón, J. and McConnell, M.J.* Activity of host antimicrobials against multidrug resistant Acinetobacter baumannii acquiring colistin resistance through loss of lipopolysaccharide. Antimicrobial Agents and Chemotherapy 2014. May;58(5):2972-5.
PUBMED DOICharacterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors
Characterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors. González N, McKee K, Lynch RM, Georgiev IS, Jimenez L, Grau E, Yuste E, Kwong PD, Mascola JR, Alcamí J. PLoS One. 2018;13:e0193773.
PUBMED DOIDiverse large HIV-1 non-subtype B clusters are spreading among men who have sex with men in Spain
Delgado E, Benito S, Montero V, Cuevas MT, Fernández-García A, Sánchez-Martínez M, García-Bodas E, Díez-Fuertes F, Gil H, Cañada J, Carrera C, Martínez-López J, Sintes M, Pérez-Álvarez L, Thomson MM; Spanish Group for the Study of New HIV Diagnoses. Diverse large HIV-1 non-subtype B clusters are spreading among men who have sex with men in Spain. Front Microbiol. 2019; 3;10:655.
PUBMED DOIImprovement of HIV-1 coreceptor tropism prediction by employing selected nucleotide positions of the env gene in a Bayesian network classifier.
Díez-Fuertes F, Delgado E, Vega Y, Fernández-García A, Cuevas MT, Pinilla M, García V, Pérez-Álvarez L, Thomson MM. Improvement of HIV-1 coreceptor tropism prediction by employing selected nucleotide positions of the env gene in a Bayesian network classifier. J Antimicrob Chemother. 2013; 68:1471-1485.
PUBMED DOIPredominance of CXCR4 tropism in HIV-1 CRF14_BG strains from newly diagnosed infections.
Pérez-Álvarez L, Delgado E, Vega Y, Montero V, Cuevas T, Fernández-García A, García-Riart B, Pérez-Castro S, Rodríguez-Real R, López-Álvarez MJ, Fernández-Rodríguez R, Lezaun MJ, Ordóñez P, Ramos C, Bereciartua E, Calleja S, Sánchez-García AM, Thomson MM. Predominance of CXCR4 tropism in HIV-1 CRF14_BG strains from newly diagnosed infections. J Antimicrob Chemother. 2014; 69:246-253.
PUBMED DOIMolecular epidemiology, phylogeny, and phylodynamics of CRF63_02A1, a recently originated HIV-1 circulating recombinant form spreading in Siberia.
Shcherbakova NS, Shalamova LA, Delgado E, Fernández-García A, Vega Y, Karpenko LI, Ilyichev AA, Sokolov YV, Shcherbakov DN, Pérez-Álvarez L, Thomson MM. Molecular epidemiology, phylogeny, and phylodynamics of CRF63_02A1, a recently originated HIV-1 circulating recombinant form spreading in Siberia. AIDS Res Hum Retroviruses. 2014; 30:912-919.
PUBMED DOIEpidemiological surveillance of HIV-1 transmitted drug resistance in Spain in 2004-2012: relevance of transmission clusters in the propagation of resistance mutations.
Vega Y, Delgado E, Fernández-García A, Cuevas MT, Thomson MM, Montero V, Sánchez M, Sánchez AM, Pérez-Álvarez L; Spanish Group for the Study of New HIV-1 Diagnoses in Galicia and Basque Country. Epidemiological surveillance of HIV-1 transmitted drug resistance in Spain in 2004-2012: relevance of transmission clusters in the propagation of resistance mutations. PLoS One. 2015; 10:e0125699.
PUBMED DOIPhylogeny and phylogeography of a recent HIV-1 subtype F outbreak among men who have sex with men in Spain deriving from a cluster with a wide geographic circulation in Western Europe.
Delgado E, Cuevas MT, Domínguez F, Vega Y, Cabello M, Fernández-García A, Pérez-Losada M, Castro MÁ, Montero V, Sánchez M, Mariño A, Álvarez H, Ordóñez P, Ocampo A, Miralles C, Pérez-Castro S, López-Álvarez MJ, Rodríguez R, Trigo M, Diz-Arén J, Hinojosa C, Bachiller P, Hernáez-Crespo S, Cisterna R, Garduño E, Pérez-Álvarez L, Thomson MM. Phylogeny and phylogeography of a recent HIV-1 subtype F outbreak among men who have sex with men in Spain deriving from a cluster with a wide geographic circulation in Western Europe. PLoS One. 2015; 10:e0143325.
PUBMED DOIIdentification of an HIV-1 BG intersubtype recombinant form (CRF73_BG), partially related to CRF14_BG, which Is circulating in Portugal and Spain.
Fernández-García A, Delgado E, Cuevas MT, Vega Y, Montero V, Sánchez M, Carrera C, López-Álvarez MJ, Miralles C, Pérez-Castro S, Cilla G, Hinojosa C, Pérez-Álvarez L, Thomson MM. Identification of an HIV-1 BG intersubtype recombinant form (CRF73_BG), partially related to CRF14_BG, which Is circulating in Portugal and Spain. PLoS One. 2016; 11:e0148549.
PUBMED DOISequence analysis of in vivo-expressed HIV-1 spliced RNAs reveals the usage of new and unusual splice sites by viruses of different subtypes
Vega Y, Delgado E, de la Barrera J, Carrera C, Zaballos Á, Cuesta I, Mariño A, Ocampo A, Miralles C, Pérez-Castro S, Álvarez H, López-Miragaya I, García-Bodas E, Díez-Fuertes F, Thomson MM. Sequence analysis of in vivo-expressed HIV-1 spliced RNAs reveals the usage of new and unusual splice sites by viruses of different subtypes. PLoS One. 2016; 11:e0158525.
PUBMED DOIHIV-1 genetic diversity in recently diagnosed infections in Moscow: predominance of AFSU, frequent branching in clusters, and circulation of the Iberian subtype G variant.
Karamov E, Epremyan K, Siniavin A, Zhernov Y, Cuevas MT, Delgado E, Sánchez-Martínez M, Carrera C, Kornilaeva G, Turgiev A, Bacqué J, Pérez-Álvarez L, Thomson MM. HIV-1 genetic diversity in recently diagnosed infections in Moscow: predominance of AFSU, frequent branching in clusters, and circulation of the Iberian subtype G variant. AIDS Res Hum Retroviruses. 2018; 34:629-634.
PUBMED DOIBayesian phylogeographic analyses clarify the origin of the HIV-1 subtype A variant circulating in former Soviet Union's countries.
Díez-Fuertes F, Cabello M, Thomson MM. Bayesian phylogeographic analyses clarify the origin of the HIV-1 subtype A variant circulating in former Soviet Union's countries. Infect Genet Evol. 2015; 33:197-205.
PUBMED DOIAlcazar-Fuoli L, Clavaud C, Lamarre C, Aimanianda V, Seidl-Seiboth V, Mellado E, Latgé JP. Functional analysis of the fungal/plant class chitinase family in Aspergillus fumigatus.
Alcazar-Fuoli L, Clavaud C, Lamarre C, Aimanianda V, Seidl-Seiboth V, Mellado E, Latgé JP. Functional analysis of the fungal/plant class chitinase family in Aspergillus fumigatus. Fungal Genet Biol. 2011 Apr;48(4):418-29. doi: 10.1016/j.fgb.2010.12.007. Epub 2010 Dec 22. PMID: 21184840.
PUBMED DOIImpact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study.
Jiménez-Sousa MA (AC); Gómez-Moreno AZ; Pineda-Tenor D; et al. (1/9) Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study. Biomolecules 2019; 9(4).
DBP rs16846876 and rs12512631 polymorphisms are associated with progression to AIDS naïve HIV-infected patients: a retrospective study.
Jiménez-Sousa MA (AC); Jiménez JL; Fernández-Rodríguez A; et al. (1/10). DBP rs16846876 and rs12512631 polymorphisms are associated with progression to AIDS naïve HIV-infected patients: a retrospective study. Journal of Biomedical Science. 2019; 23;26(1):83. doi: 10.1186/s12929-019-0577-y.
TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients.Journal of Clinical Medicine.
Resino S; Fernández-Rodríguez A; Pineda-Tenor D; et al; Jiménez-Sousa MA. (11/11). 2021. TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients.Journal of Clinical Medicine. 10-3, pp.483. ISSN 2077-0383. https://doi.org/10.3390/jcm10030483.
Plasma metabolomic fingerprint of advanced cirrhosis stages among HIV/HCV-coinfected and HCV-monoinfected patients
Salguero, Sergio; Rojo, David; Berenguer, Juan; et al; Jimenez-Sousa, Maria A. (AC) (15/15). 2020. Plasma metabolomic fingerprint of advanced cirrhosis stages among HIV/HCV-coinfected and HCV-monoinfected patients LIVER INTERNATIONAL. 40-9, pp.2215-2227. ISSN 1478-3223. https://doi.org/10.1111/liv.14580 3
Content with Investigacion .
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Leticia Bernal Martínez
Staff Scientist
ORCID code: 0000-0002-1694-5522
Dr. Bernal-Martínez obtained her degree in Biochemistry from the University of Zaragoza in 2005. She joined the Mycology Reference and Research Laboratory (LRIM) in 2006 under a trainee contract and completed her PhD within the Official Doctoral Program in Microbiology and Parasitology at the Complutense University of Madrid, defending her thesis in 2010 with highest honors (Cum Laude). In 2007, she continued her research activity at LRIM within the framework of the Spanish Network for Research in Infectious Diseases (REIPI). In 2016, she completed a Postgraduate Diploma in Promotion and Management of International Projects (Technical University of Madrid) and undertook a research stay at the Microbiology and Infection Research Domain, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho (Braga, Portugal). She was subsequently appointed as a PhD researcher within the Biomedical Research Networking Center in Infectious Diseases (CIBERINFEC). Since 2024, she serves as Specialist Scientist at the Carlos III Health Institute (ISCIII) and is responsible for the Diagnostic and Serology Section for Endemic Fungi at the Mycology Reference and Research Laboratory.
Dr. Bernal-Martínez has authored more than 30 peer-reviewed scientific publications and two book chapters. She has actively participated in over 12 research projects and has presented her work at numerous national and international scientific conferences. Her research has focused on human fungal infections, antifungal resistance, therapeutic drug monitoring, genetic variants associated with antifungal metabolism, and the identification of predictive biomarkers of invasive fungal infections. However, her primary expertise lies in the diagnostic field, particularly in the design, optimization, and validation of real-time PCR–based methodologies.
She is currently Principal Investigator of a research project aimed at improving current diagnostic techniques for invasive fungal infections, evaluating emerging diagnostic technologies, and studying primary fungal pathogens. A substantial part of her work has been transferred to the Spanish National Health System and to research centers in Latin America. Many of the diagnostic methodologies developed have been incorporated into the official service portfolio of ISCIII. She has collaborated with multiple hospitals through research projects and clinical trials applying these technologies, as well as with the ISCIII spin-off company Micomol S.L.
Dr. Bernal-Martínez has supervised several Master’s and Undergraduate Final Degree Projects from students at the Complutense University of Madrid and the University of Alcalá. She is a member of the teaching staff of the UNED-ISCIII PhD Program in Biomedical Sciences and Public Health and serves as lecturer in the Master’s Program in Public Health and Research in Infectious Diseases at the University of Alcalá. -

Laura Alcázar Fuoli
Research Scientist
Graduated in Biochemistry from the Autonomous University of Madrid and PhD in Biology from the Complutense University of Madrid in 2006. She completed her doctoral thesis at the National Center of Microbiology (CNM) under the direction of Dr. Emilia Mellado, in the study of the synthesis of Ergosterol in Aspergillus fumigatus. In 2012 Laura joined the reference laboratory in mycology with a researcher contract for the “Miguel Servet” program after having worked for three years as an associate researcher at Imperial College London. During that period his research focused on host adaptation mechanisms and virulence factors of A. fumigatus. In 2014 he obtained the position of Senior Scientist of Public Research Organizations carrying out his research work at the CNM.
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.