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Investigation
Viral Biology
Research Lines
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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
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- 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
pective comparative multi-centre study on imported Plasmodium ovale wallikeri and Plasmodium ovale curtisi infections.
Rojo-Marcos G, Rubio-Muñoz JM, Angheben A, Jaureguiberry S, García-Bujalance S, Tomasoni LR, Rodríguez-Valero N, Ruiz-Giardín JM, Salas-Coronas J, Cuadros-González J, García-Rodríguez M, Molina-Romero I, López-Vélez R, Gobbi F, Calderón-Moreno M, Martin-Echevarría E, Elía-López M, Llovo-Taboada J; TropNet Plasmodium ovale investigator group. Prospective comparative multi-centre study on imported Plasmodium ovale wallikeri and Plasmodium ovale curtisi infections. Malar J. 2018 Oct 30;17(1):399.
PUBMED DOIImported and autochthonous malaria in West Saudi Arabia: results from a reference hospital
Soliman RH, Garcia-Aranda P, Elzagawy SM, Hussein BE, Mayah WW, Martin Ramirez A, Ta-Tang TH, Rubio JM. Imported and autochthonous malaria in West Saudi Arabia: results from a reference hospital. Malar J. 2018 Aug 7;17(1):286.
PUBMED DOICryptosporidium hominis genotypes involved in increased incidence and clusters of cases, Navarra, Spain, 2012.
Fuentes, I., Martín, C., Beristain, X; Mazón,A, Saugar, JM, Blanco, A; García M, Cenoz, Valle-Cristia, Ezpeleta, C., Castilla, J. 2015. Cryptosporidium hominis genotypes involved in increased incidence and clusters of cases, Navarra, Spain, 2012. Epidemiology and Infection; 143:1033-6
PUBMED DOIMolecular genotyping of Giardia duodenalis isolates from symptomatic individuals attending two major public hospitals in Madrid, Spain.
Lucio A, Martínez-Ruiz R, Merino FJ, Bailo B, Aguilera M, Fuentes I, Carmena D. 2015. Molecular genotyping of Giardia duodenalis isolates from symptomatic individuals attending two major public hospitals in Madrid, Spain. PLoS One. 10 (12): e0143981.
PUBMED DOIOccurrence and subtype distribution of Blastocystis sp. in humans, dogs, and cats sharing household in northern Spain and assessment of zoonotic transmission risk.
Paulos S, Köster PC, de Lucio A, Hernández-de-Mingo M, Cardona GA, Fernández-Crespo JC, Stensvold RC, Carmena D. 2018. Occurrence and subtype distribution of Blastocystis sp. in humans, dogs, and cats sharing household in northern Spain and assessment of zoonotic transmission risk. Zoonoses and Public Health, 65:993-1002.
PUBMED DOIPhlebotomine sand fly survey in the focus of leishmaniasis of Madrid, Spain (2012–2014): seasonal dynamics, Leishmania infantum infection rates and blood meal preferences.
González E, Jiménez M, Hernández S, Martín-Martín I, Molina R. Phlebotomine sand fly survey in the focus of leishmaniasis of Madrid, Spain (2012–2014): seasonal dynamics, Leishmania infantum infection rates and blood meal preferences. Parasit Vectors 2017, 10:368.
PUBMED DOIMethods in Sand Fly Research
Molina R, Jiménez M, Alvar J, González E, Hernández-Taberna S, Martín-Martín Inés. 2017. Methods in Sand Fly Research (R. Molina, M. Jiménez & J. Alvar, edits.). Servicio de Publicaciones Universidad de Alcalá de Henares. ISBN: 978-84-16978-28-1
Factors associated with Leishmania asymptomatic infection: results from a cross-sectional survey in highland northern Ethiopia
Custodio E, Gadisa E, Sordo L, Cruz I, Moreno J, Nieto J, Chicharro C, Aseffa A, Abraham Z, Hailu T, Cañavate C. Factors associated with Leishmania asymptomatic infection: results from a cross-sectional survey in highland northern Ethiopia. PLoS Negl Trop Dis. 2012;6(9):e1813.
PUBMED DOICytokine Release Assays as Tests for Exposure to Leishmania, and for Confirming Cure from Leishmaniasis, in Solid Organ Transplant Recipients.
Carrillo E, Carrasco-Antón N, López-Medrano F, Salto E, Fernández L, San Martín JV, Alvar J, Aguado JM, Moreno J. Cytokine Release Assays as Tests for Exposure to Leishmania, and for Confirming Cure from Leishmaniasis, in Solid Organ Transplant Recipients. PLoS Negl Trop Dis. 2015 Oct 23;9(10):e0004179.
PUBMED DOIChemotactic Protein 1 in Plasma from Soluble Leishmania Antigen-Stimulated Whole Blood as a Potential Biomarker of the Cellular Immune Response to Leishmania infantum
Ibarra-Meneses AV, Sanchez C, Alvar J, Moreno J, Carrillo E. Monocyte Chemotactic Protein 1 in Plasma from Soluble Leishmania Antigen-Stimulated Whole Blood as a Potential Biomarker of the Cellular Immune Response to Leishmania infantum. Front Immunol. 2017 Sep 29;8:1208.
PUBMED DOICytokines and chemokines measured in dried SLA-stimulated whole blood spots for asymptomatic Leishmania infantum and Leishmania donovani infection.
Ibarra-Meneses AV, Mondal D, Alvar J, Moreno J, Carrillo E. Cytokines and chemokines measured in dried SLA-stimulated whole blood spots for asymptomatic Leishmania infantum and Leishmania donovani infection. Sci Rep. 2017 Dec 8;7(1):17266.
PUBMED DOICellular Markers of Active Disease and Cure in Different Forms of Leishmania infantum-Induced Disease.
Botana L, Matía B, San Martin JV, Romero-Maté A, Castro A, Molina L, Fernandez L, Ibarra-Meneses A, Aguado M, Sánchez C, Horrillo L, Chicharro C, Nieto J, Ortega S, Ruiz-Giardin JM, Carrillo E, Moreno J. Cellular Markers of Active Disease and Cure in Different Forms of Leishmania infantum-Induced Disease. Front Cell Infect Microbiol. 2018 Nov 13;8:381.
PUBMED DOICarroll MW et al. Temporal and spatial analysis of the 2014-2015 Ebola virus outbreak in West Africa. Nature.
Carroll MW et al. Temporal and spatial analysis of the 2014-2015 Ebola virus outbreak in West Africa. Nature. 2015 Aug 6;524(7563):97-101. doi: 10.1038/nature14594. Epub 2015 Jun 17. PMID: 26083749.
Fernandez-Garcia MD, Meertens L, Chazal M, Hafirassou ML, Dejarnac O, Zamborlini A, Despres P, Sauvonnet N, Arenzana-Seisdedos F, Jouvenet N, Amara A. Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses.
Fernandez-Garcia MD, Meertens L, Chazal M, Hafirassou ML, Dejarnac O, Zamborlini A, Despres P, Sauvonnet N, Arenzana-Seisdedos F, Jouvenet N, Amara A. Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses. mBio. 2016 Feb 9;7(1):e01956-15. doi: 10.1128/mBio.01956-15. PMID: 26861019; PMCID:PMC4752603.
Identification and whole-genome characterization of a recombinant Enterovirus B69 isolated from a patient with Acute Flaccid Paralysis in Niger, 2015
Fernandez-Garcia MD, Majumdar M, Kebe O, Ndiaye K, Martin J. Identification and whole-genome characterization of a recombinant Enterovirus B69 isolated from a patient with Acute Flaccid Paralysis in Niger, 2015. Sci Rep. 2018 Feb 1;8(1):2181. doi: 10.1038/s41598-018-20346-9. PMID: 29391547; PMCID: PMC5795009.
Majumdar M, Sharif S, Klapsa D, Wilton T, Alam MM, Fernandez-Garcia MD, Rehman L, Mujtaba G, McAllister G, Harvala H, Templeton K, Mee ET, Asghar H, Ndiaye K, Minor PD, Martin J. Environmental Surveillance Reveals Complex Enterovirus Circulation Patterns in Human Populations. Open Forum Infect Dis. 2018
Majumdar M, Sharif S, Klapsa D, Wilton T, Alam MM, Fernandez-Garcia MD, Rehman L, Mujtaba G, McAllister G, Harvala H, Templeton K, Mee ET, Asghar H, Ndiaye K, Minor PD, Martin J. Environmental Surveillance Reveals Complex Enterovirus Circulation Patterns in Human Populations. Open Forum Infect Dis. 2018 Oct 1;5(10):ofy250. doi: 10.1093/ofid/ofy250. PMID: 30377626; PMCID: PMC6201154.
Fernandez-Garcia MD, Majumdar M, Kebe O, Fall AD, Kone M, Kande M, Dabo M, Sylla MS, Sompare D, Howard W, Faye O, Martin J, Ndiaye K. Emergence of Vaccine-Derived Polioviruses during Ebola Virus Disease Outbreak, Guinea, 2014-2015.
Fernandez-Garcia MD, Majumdar M, Kebe O, Fall AD, Kone M, Kande M, Dabo M, Sylla MS, Sompare D, Howard W, Faye O, Martin J, Ndiaye K. Emergence of Vaccine-Derived Polioviruses during Ebola Virus Disease Outbreak, Guinea, 2014-2015. Emerg Infect Dis. 2018 Jan;24(1):65-74. doi: 10.3201/eid2401.171174. PMID:29260690; PMCID: PMC5749474.
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Almudena Cascajero Díaz
Técnico de laboratorio
ORCID code: 0000-0002-9654-3100
Técnico Superior de Actividades Técnicas y Profesionales (Unidades de Inmunopatología del SIDA y Legionella, Centro Nacional de Microbiología). Clinical Diagnostic Laboratory Technician by IES Renacimiento de Madrid.
Experience in cloning techniques and characterization of neutralizing antibodies and participation in different projects on the pathogenesis of HIV by studying the viral envelope and the mechanisms of resistance to antiretroviral drugs. This experience has subsequently allowed me to participate in 5 multicenter clinical studies studying the immune response against different variants of SARS-CoV-2.
Since 2021, I also participate as a laboratory technician in the Legionella Unit as a support to the Spanish National Health System through the microbiological surveillance of the disease to contribute to the prevention and control of legionellosis.
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Laura del Estal Gómez
Ayudante de investigación
ORCID code: 0009-0000-2773-8986
Graduada en Biología Sanitaria por la Universidad de Alcalá. Máster Universitario en Microbiología Aplicada a la Salud Pública e Investigación en Enfermedades Infecciosas.
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Caroline Stephanie Crisóstomo Vergara
Técnico de Laboratorio
ORCID code: 0009-0008-0525-1737
Técnico de Laboratorio. Técnico superior de Laboratorio Clínico y Biomédico por la Escuela Técnica de Enseñanzas Especializadas de Madrid. Máster en Microbiología Clínica por el Instituto Europeo de Química, Física y Biología de Madrid.
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Fernando González Camacho
Científico Titular
ORCID code: 0000-0003-3175-9004
Licenciado en Ciencias Biológicas por la Universidad de Salamanca y Doctor por la Universidad Autónoma de Madrid. Actualmente, es Científico Titular de plantilla en el Centro Nacional de Microbiología (CNM) del Instituto de Salud Carlos III (ISCIII). Responsable de la Unidad de Legionella del Laboratorio de Referencia e Investigación en Enfermedades Bacterianas transmitidas por agua y alimentos.
A nivel europeo es sustituto (Alternate) al National Focal Point para la enfermedad del legionario en el ECDC y es OCP (Operational Contact Point) en microbiología para la legionelosis en la European Legionnaires' Disease Surveillance Network (ELDSNet).
Coordina las líneas de investigación del laboratorio que se desarrollan en tres perspectivas diferentes: en las instalaciones colonizadas, estudios sobre la resistencia a los tratamientos y su persistencia; en la clínica, sobre factores de virulencia y su interacción con el sistema inmune; y en la vigilancia microbiológica, sobre la mejorar de los métodos de caracterización del microorganismo.
Es Investigador Principal en el proyecto “Búsqueda de biomarcadores de patogenicidad en Legionella spp con interés predictivo de riesgo de infección".
Es miembro de distintas sociedades científicas como son la Sociedad Española de Salud Ambiental (SESA), Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) y la European Society of Clinical Microbiology and Infectious Diseases (ESCMID).
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Juana María González Rubio
Científica Titular
ORCID code: 0000-0001-6979-2964
La Dra. Juana María González Rubio es Licenciada en Bioquímica por la Universidad de Salamanca y Doctora por la Facultad de Medicina de la Universidad Autónoma de Madrid. Actualmente, es Científico Titular de plantilla en el Centro Nacional de Microbiología del Instituto de Salud Carlos III (ISCIII), donde trabaja en la Unidad de Legionella del Laboratorio de Referencia e Investigación en Enfermedades Bacterianas transmitidas por agua y alimentos.
Dentro del laboratorio, realiza las actividades propias del Programa de Vigilancia Microbiológica de Legionella, y lleva las líneas de investigación del laboratorio sobre la caracterización de biofilms y la puesta a punto de nuevas técnicas para la caracterización de Legionella. También forma parte del equipo investigador del proyecto “Búsqueda de marcadores de patogenicidad para el análisis de riesgos en las instalaciones".
Anteriormente, ha trabajado en la Unidad de Biomonitorización humana del Centro Nacional de Sanidad Ambiental (ISCIII) participando en diferentes proyectos de investigación relacionados con la Sanidad Ambiental, siendo el último más destacado el proyecto “HBM4EU" en el que ha trabajado hasta junio de 2023.
List of staff
Additional Information
The research activity of the Viral Biology group since its beginnings in the 1980s has focused on respiratory viruses, especially on the study of the mechanisms of virus entry into the cell, evolutionary aspects, antigenic properties and vaccine development.
Currently, the group's objectives are focused on the characterisation of the immune response and the development of vaccines against human pneumoviruses: human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV).
Both viruses are considered to be important respiratory pathogens of high clinical relevance, especially in the paediatric population.
Safe and effective vaccines against these viruses are currently not available. Soluble protein subunits based on the fusion protein (F-protein) of hRSV and hMPV are being developed in the laboratory by protein engineering for use as vaccines against human pneumoviruses.
On the other hand, and thanks to the characterisation of the type of humoral response induced by the F proteins of these viruses, the laboratory is also involved in the isolation of monoclonal antibodies and nanoantibodies for use as treatments against these viruses.
The research activity of the Viral Biology group since its beginnings in the 1980s has focused on respiratory viruses, especially on the study of the mechanisms of virus entry into the cell, evolutionary aspects, antigenic properties and vaccine development.
Currently, the group's objectives are focused on the characterisation of the immune response and the development of vaccines against human pneumoviruses: human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV).
Both viruses are considered to be important respiratory pathogens of high clinical relevance, especially in the paediatric population.
Safe and effective vaccines against these viruses are currently not available. Soluble protein subunits based on the fusion protein (F-protein) of hRSV and hMPV are being developed in the laboratory by protein engineering for use as vaccines against human pneumoviruses.
On the other hand, and thanks to the characterisation of the type of humoral response induced by the F proteins of these viruses, the laboratory is also involved in the isolation of monoclonal antibodies and nanoantibodies for use as treatments against these viruses.