Respiratory viruses and Influenza
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
Characterization of an enhanced antigenic change in the pandemic 2009 H1N1 influenza virus haemagglutinin
Garcia-Barreno B, Delgado T, Benito S, Casas I, Pozo F, Cuevas MT, et al. Characterization of an enhanced antigenic change in the pandemic 2009 H1N1 influenza virus haemagglutinin. J Gen Virol. 2014;95(Pt 5):1033-42.
PUBMED DOIEpidemic history of hepatitis C virus genotypes and subtypes in Portugal.
Palladino C, Ezeonwumelu IJ, Marcelino R, Briz V, Moranguinho I, Serejo F, Velosa JF, Tato Marinho R, Borrego P, Taveira N. 2018. Epidemic history of hepatitis C virus genotypes and subtypes in Portugal. Sci Rep. 2018; 8:12266. (A; FI= 4.12; Q1 Multidisciplinary Sciences; DOI:10.1038/s41598-018-30528-0).
PUBMED DOILow frequency of NS5A relevant resistance-associated substitutions to Elbasvir among hepatitis C virus genotype 1a in Spain: a cross-sectional study.
Palladino C, Sanchez-Carrillo M, Mate-Cano I, Vazquez-Morón S, Jiménez-Sousa MA, Gutiérrez-Rivas M, Resino S, Briz V. Low frequency of NS5A relevant resistance-associated substitutions to Elbasvir among hepatitis C virus genotype 1a in Spain: a cross-sectional study. Sci Rep. 2017; 7(1):2892. (A; FI= 4.12; Q1 Multidisciplinary Sciences).
PUBMED DOIPlasma miRNA profile at COVID-19 onset predicts severity status and mortality.
Fernández-Pato A; Virseda-Berdices A, Ryan P; Martínez-González O, Peréz-García F, Resino S, Martin-Vicente M, Valle-Millares D, Brochado-Kith O; Blancas R; Ceballos FC; Bartolome-Sánchez S; Vidal-Alcántara EJ; Alonso-Menchén D, Blanca-López N; Ramirez Martinez-Acitores I, Rava M, Jiménez-Sousa MA (‡ *), Amanda Fernández-Rodríguez (‡ *). Plasma miRNA profile at COVID-19 onset predicts severity status and mortality. Emerg Microbes Infect 2022; 11(1):676-688 (A; FI= 19.57; 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).
PUBMED DOIEfficacy of DNA amplification in tissue biopsy samples to improve the detection of invasive fungal disease
Buitrago MJ, Aguado JM, Ballen A, Bernal-Martinez L, Prieto M, Garcia-Reyne A, Garcia-Rodriguez J, Rodriguez-Tudela JL, Cuenca-Estrella M. Efficacy of DNA amplification in tissue biopsy samples to improve the detection of invasive fungal disease. Clin Microbiol Infect. 2013 Jun;19(6):E271-7. doi: 10.1111/1469-0691.12110. Epub 2013 Mar 7. PMID: 23464751.
PUBMED DOIPotent Induction of Envelope-Specific Antibody Responses by Virus-Like Particle Immunogens Based on HIV-1 Envelopes from Patients with Early Broadly Neutralizing Responses
Beltran-Pavez C, Bontjer I, Gonzalez N, Pernas M, Merino-Mansilla A, Olvera A, Miro JM, Brander C, Alcami J, Sanders RW, Sanchez-Merino V, Yuste E. J Virol. 2022 Jan 12, 96(1): e0134321
PUBMED DOIHIV-1 envelope glycoproteins isolated from Viremic Non-Progressor individuals are fully functional and cytopathic
Cabrera-Rodríguez R, Hebmann V, Marfil S, Pernas M, Marrero-Hernández S, Cabrera C, Urrea V, Casado C, Olivares I, Márquez-Arce D, Pérez-Yanes S, Estévez-Herrera J, Clotet B, Espert L, López-Galíndez C, Biard-Piechaczyk M, Valenzuela-Fernández A, Blanco J. Sci Rep. 2019 Apr 3,9(1):5544
PUBMED DOIViral Characteristics Associated with the Clinical Nonprogressor Phenotype Are Inherited by Viruses from a Cluster of HIV-1 Elite Controllers
Casado C, Marrero-Hernández S, Márquez-Arce D, Pernas M, Marfil S, Borràs-Grañana F, Olivares I, Cabrera-Rodríguez R, Valera MS, de Armas-Rillo L, Lemey P, Blanco J, Valenzuela-Fernández A, Lopez-Galíndez C. mBio. 2018 Apr 10,9(2): e02338-17
PUBMED DOIViral and Cellular Factors Leading to the Loss of CD4 Homeostasis in HIV-1 Viremic Nonprogressors.
Colomer-Lluch M, Kilpelainen A, Pernas M, Peña R, Ouchi D, Jimenez-Moyano E, Dalmau J, Casado C, López-Galíndez C, Clotet B, Martinez-Picado J, Prado JG. J Virol. 2022 Jan 12, 96(1): e0149921. doi: 10.1128/JVI.01499-21. Epub 2021 Oct 20.
PUBMED DOIContribution of the HIV-1 Envelope Glycoprotein to AIDS Pathogenesis and Clinical Progression
Valenzuela-Fernández A, Cabrera-Rodríguez R, Casado C, Pérez-Yanes S, Pernas M, García-Luis J, Marfil S, Olivares I, Estévez-Herrera J, Trujillo-González R, Blanco J, Lopez-Galindez C. Biomedicines. 2022 Sep 2,10(9):2172.
PUBMED DOIPrevalence of HIV-1 dual infection in LTNP-Elite Controllers
María Pernas, Concepción Casado, Virginia Sandonis, Carolina Arcones, Carmen Rodríguez , Ezequiel Ruiz-Mateos , Eva Ramírez de Arellano , Norma Rallón , Margarita Del Val , Eulalia Grau, Mariola López-Vazquez , Manuel Leal , Jorge del Romero , Cecilio López Galíndez . (2013). J.of AIDS. 64, 3, 225-231. IF 4.262
PUBMED DOIA Genome-to-Genome Analysis of Associations between Human Genetic Variation, HIV-1 Sequence Diversity, and Retroviral Control.
Istvan Bartha Jonathan M Carlson, Chanson J Brumme, Paul J McLaren, Zabrina L Brumme, Mina John, David W Haas, Javier Martinez-Picado, Cecilio López Galíndez, Andri Rauch, Huldrych F Günthard, Enos Bernasconi, Pietro Vernazza, Thomas Klimkait, Sabine Yerly, Jennifer Listgarten, Nico Pfeifer, Zoltan Kutalik, Todd M Allen, Viktor Müller, P Richard Harrigan, David Heckerman, Amalio Telenti, and Jacques Fellay, for the HIV Genome-to-Genome Study and the Swiss HIV Cohort Study. (2013). Elife. 2013;2:e01123
PUBMED DOIFactors Leading to the Loss of Natural Elite Control of HIV-1 Infection
Pernas M, Tarancón-Diez L, Rodríguez-Gallego E, Gómez J, Prado JG, Casado C, Dominguez-Molina B, Olivares I, Coiras M, León A, Rodriguez C, Benito JM, Rallón N, Plana M, Martinez-Madrid O, Dapena M, Iribarren JA, Del Romero J, García F, Alcamí J, Muñoz-Fernández M, Vidal F, Leal M, Lopez-Galindez C, Ruiz-Mateos E. J Virol. 2018 Feb 12,92(5): e01805-17
PUBMED DOIContent with Investigacion .
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Sara Vázquez Ávila
Técnico de Laboratorio
Obtuve mi título como Técnico de Laboratorio Clínico y Biomédico en el año 2020 y en el 2021obtuve el Grado Superior de Anatomía Patológica y Citodiagnóstico. Trabajé en el Centro Andaluz de Biología Molecular y Medicina Regenerativa (Sevilla) y en el Departamento de Farmacología de la Facultad de Medicina (Universidad Complutense de Madrid). Actualmente soy Técnico de Laboratorio en el Laboratorio de Helmintos del CNM (ISCIII).
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Maria Jesús Perteguer Prieto
Investigadora Titular, Jefa de grupo
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Javier Sotillo Gallego
Científico Titular
ORCID code: 0000-0002-1443-7233
En el año 2011 obtuve mi título de doctor “cum laude” por la Universidad de Valencia. Durante mi etapa postdoctoral en la James Cook University en Australia (2012-2019) me especialicé en estudiar las interacciones parásito-hospedador usando diferentes técnicas ómicas. En 2019 volví España y comencé a trabajar en el Laboratorio de Helmintos del CNM (ISCIII) primero como Investigador Miguel Servet y más adelante como Investigador Ramón y Cajal. Actualmente soy Científico Titular en el mismo laboratorio.
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Ana Hernández González
Laboral Fijo Doctor
ORCID code: 0000-0001-6762-8175
Licenciada en Biología y doctora en Enfermedades Tropicales por la Universidad de Salamanca. Puestos ocupados con anterioridad: investigadora predoctoral en el IRNASA-CSIC (contrato JAE predoc), investigadora postdoctoral en el CNM (contrato Sara Borrell) e investigadora contratada como técnico superior en el CNM (RICET). Actualmente, personal Laboral Fijo Doctor en el laboratorio de Helmintos del CNM.
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Esther Rodríguez Pérez
Técnico de Laboratorio
ORCID code: 0000-0002-3680-7733
Obtuve mi título como Graduada en Biología Sanitaria en el año 2015 y en el año 2019 obtuve el Grado Superior de Laboratorio de Diagnóstico Clínico. De 2019 a 2022 trabajé en el Museo Nacional de Ciencias Naturales (MNCN-CSIC), en el Departamento de Biogeoquímica y Ecología Microbiana. Actualmente trabajo como Técnico de Laboratorio en el Laboratorio de Helmintos del CNM (ISCIII).
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Lourdes Castro Companioni
Ayudante de Investigación
ORCID code: 0009-0003-2746-4067
Bióloga sanitaria graduada en la Universidad de Alcalá de Henares (UAH), con master de Microbiología y Salud pública en la UAH en colaboración con el ISCIII.
List of staff
Additional Information
The Respiratory Viruses and Influenza Unit is the oldest WHO Influenza Center in our country (1968), designated as the National Influenza Center by the Ministry of Health in 1971, and is the national coordinator of the CCAA laboratories in the National Influenza Surveillance Network of the Influenza Surveillance System in Spain.
Its general objective is virological surveillance, detection and control of influenza in Spain. Since 1992, together with the Pediatric Service of the Severo Ochoa Hospital, a line of research has been developed based on the etiological study of viral respiratory infections in hospitalized children.
Since 2015, the La Paz Children's University Hospital and the Immunology Laboratory of the IIS-Fundación Jiménez Díaz have also participated, expanding the study to newborns and neonatal units.
To comprehensively study respiratory viruses and the response of the immune system in viral respiratory infections that affect newborns and pediatric patients.
Deepen the knowledge of the biological properties of the viruses involved in the disease: dependency/facilitation, balance between viruses and their adaptation in multiple infections, relationship with severity, existence of virome imbalance.
The Respiratory Viruses and Influenza Unit is the oldest WHO Influenza Center in our country (1968), designated as the National Influenza Center by the Ministry of Health in 1971, and is the national coordinator of the CCAA laboratories in the National Influenza Surveillance Network of the Influenza Surveillance System in Spain.
Its general objective is virological surveillance, detection and control of influenza in Spain. Since 1992, together with the Pediatric Service of the Severo Ochoa Hospital, a line of research has been developed based on the etiological study of viral respiratory infections in hospitalized children.
Since 2015, the La Paz Children's University Hospital and the Immunology Laboratory of the IIS-Fundación Jiménez Díaz have also participated, expanding the study to newborns and neonatal units.
To comprehensively study respiratory viruses and the response of the immune system in viral respiratory infections that affect newborns and pediatric patients.
Deepen the knowledge of the biological properties of the viruses involved in the disease: dependency/facilitation, balance between viruses and their adaptation in multiple infections, relationship with severity, existence of virome imbalance.