Viral Infection and Immunity
Líneas de investigación
Content with Investigacion .
Virus entéricos
1. Vigilancia microbiológica y epidemiológica a nivel nacional de las infecciones causadas por enterovirus y parechovirus y de los casos de parálisis flácida aguda en menores de 15 años. Caracterización, asociación clínica y epidemiología molecular.
2. Investigación de los enterovirus y parechovirus que causan infecciones neurológicas y sistémicas severas en población pediátrica. Estudio de los factores virológicos implicados en la patogenicidad.
3. Estudio virológico de muestras ambientales (aguas residuales y tratadas para consumo) de la CAM.
4. Estudio virológico (diagnóstico y caracterización) de las infecciones gastrointestinales causadas por virus (norovirus, rotavirus y otros). Epidemiología molecular y caracterización de brotes.
Investigación y vigilancia de los poliovirus y la poliomielitis
El Laboratorio de Enterovirus (actualmente de Virus Entéricos) del CNM fue designado Laboratorio Nacional de Poliovirus en 1998 y desde entonces es certificado anualmente por la OMS, como parte del Plan Global de Erradicación de la Poliomielitis. Es responsable, junto a 3 laboratorios primarios en 3 CCAA, de la vigilancia de la poliomielitis a nivel nacional, estudiando e investigando (clínica, epidemiológica y virológicamente) todos los casos compatibles, incluidos los de parálisis flácida aguda en menores de 15 años (enfermedad de notificación obligatoria) para descartar la presencia y circulación de poliovirus en España.
Además, desde 1999 (y gracias a un convenio con el CYII) posee toda la infraestructura y metodología necesaria para realizar vigilancia medioambiental en aguas, tanto para medir la calidad de las aguas potables de ETAP, como para monitorizar la excreción de virus por parte de la población con el estudio de la presencia de poliovirus y otros enterovirus en aguas residuales de EDAR. Esto ha permitido que, a partir de marzo de este año, se estén realizando, además, ensayos de presencia de SARS-CoV-2 en las muestras procedentes de diferentes EDAR situadas en la CAM.
Investigación y referencia en infecciones por enterovirus y parechovirus
El Laboratorio también es Laboratorio de Referencia para las infecciones por Enterovirus y Parechovirus realizando: 1) el diagnostico virológico en muestras clínicas; 2) la caracterización de todos los enterovirus y parechovirus detectados (Programa de Vigilancia Microbiológica del CNM); 3) el desarrollo, mantenimiento y transferencia de métodos de diagnóstico y tipado, tanto moleculares como de cultivo viral; y 4) la investigación para profundizar en el conocimiento de aquellos virus implicados en casos de excepcional importancia clínica o epidemiológica. La larga experiencia del grupo en la propagación de cultivos virales de enterovirus y en técnicas celulares y moleculares de caracterización, ha permitido que el CNM posea una amplia colección de cepas, muy valiosa para la investigación de estos virus.
Investigación y referencia en infecciones gastrointestinales causadas por virus
Desde 2016, el laboratorio realiza: 1) el diagnostico virológico de Norovirus, Rotavirus, Adenovirus 40/41, Astrovirus y otros virus productores de gastroenteritis aguda en muestras clínicas; 2) el genotipado de los virus detectados y la caracterización de brotes; 3) el desarrollo y mantenimiento de métodos de diagnóstico y genotipado; y 4) la investigación básica y epidemiológica de aquellos virus de mayor importancia clínica.
Publicaciones destacadas
Cryptococcus neoformans can form titan-like cells in vitro in response to multiple signals
2. Trevijano-Contador N, de Oliveira HC, García-Rodas R, Rossi SA, Llorente I, Zaballos Á, Janbon G, Ariño J, Zaragoza Ó. Cryptococcus neoformans can form titan-like cells in vitro in response to multiple signals. PLoS Pathog. 2018 May 18;14(5):e1007007.
PUBMED DOIReclassification of the Candida haemulonii complex as Candida haemulonii (C. haemulonii group I), C. duobushaemulonii sp. nov. (C. haemulonii group II), and C. haemulonii var. vulnera var. nov.: three multiresistant human pathogenic yeasts
4. Cendejas-Bueno E, Kolecka A, Alastruey-Izquierdo A, Theelen B, Groenewald M, Kostrzewa M, Cuenca-Estrella M, Gómez-López A, Boekhout T. Reclassification of the Candida haemulonii complex as Candida haemulonii (C. haemulonii group I), C. duobushaemulonii sp. nov. (C. haemulonii group II), and C. haemulonii var. vulnera var. nov.: three multiresistant human pathogenic yeasts. J Clin Microbiol.
PUBMED DOIMolecular Identification and Susceptibility Testing of Molds Isolated in a Prospective Surveillance of Triazole Resistance in Spain (FILPOP2 Study).
5. Alastruey-Izquierdo A, Alcazar-Fuoli L, Rivero-Menéndez O, Ayats J, Castro C, García-Rodríguez J, Goterris-Bonet L, Ibáñez-Martínez E, Linares-Sicilia MJ, Martin-Gomez MT, Martín-Mazuelos E, Pelaez T, Peman J, Rezusta A, Rojo S, Tejero R, Anza DV, Viñuelas J, Zapico MS, Cuenca-Estrella M; the FILPOP2 Project from GEMICOMED (SEIMC) and REIPI. Molecular Identification and Susceptibility Testing of Molds Isolated in a Prospective Surveillance of Triazole Resistance in Spain (FILPOP2 Study). Antimicrob Agents Chemother. 2018 Aug 27;62(9).
PUBMED DOIEvaluation of Bronchoalveolar Lavage Fluid Cytokines as Biomarkers for Invasive Pulmonary Aspergillosis in At-Risk Patients
6. Gonçalves SM, Lagrou K, Rodrigues CS, Campos CF, Bernal-Martínez L, Rodrigues F, Silvestre R, Alcazar-Fuoli L, Maertens JA, Cunha C, Carvalho A. Evaluation of Bronchoalveolar Lavage Fluid Cytokines as Biomarkers for Invasive Pulmonary Aspergillosis in At-Risk Patients. Front Microbiol. 2017 Nov 29;8:2362.
PUBMED DOIPolymorphisms in Host Immunity-Modulating Genes and Risk of Invasive Aspergillosis: Results from the AspBIOmics Consortium
7. Lupiañez CB, Canet LM, Carvalho A, Alcazar-Fuoli L, Springer J, Lackner M, Segura-Catena J, Comino A, Olmedo C, Ríos R, Fernández-Montoya A, Cuenca-Estrella M, Solano C, López-Nevot MÁ, Cunha C, Oliveira-Coelho A, Villaescusa T, Fianchi L, Aguado JM, Pagano L, López-Fernández E, Potenza L, Luppi M, Lass-Flörl C, Loeffler J, Einsele H, Vazquez L; PCRAGA Study Group, Jurado M, Sainz J. Polymorphisms in Host Immunity-Modulating Genes and Risk of Invasive Aspergillosis: Results from the AspBIOmics Consortium. Infect Immun. 2015 Dec 14;84(3):643-57.
PUBMED DOICell Wall Changes in Amphotericin B-Resistant Strains from Candida tropicalis and Relationship with the Immune Responses Elicited by the Host.
9. Mesa-Arango AC, Rueda C, Román E, Quintin J, Terrón MC, Luque D, Netea MG, Pla J and Zaragoza O. Cell Wall Changes in Amphotericin B-Resistant Strains from Candida tropicalis and Relationship with the Immune Responses Elicited by the Host. Antimicrob. Agents Chemother. 2016. 60(4):2326-35.
PUBMED DOIThe role of respiratory viruses in children with humoral immunodeficiency on immunoglobulin replacement therapy
Benavides-Nieto M, Méndez-Echevarría A, Del Rosal T, García-García ML, Casas I, Pozo F, de la Serna O, Lopez-Granados E, Rodriguez-Pena R, Calvo C. The role of respiratory viruses in children with humoral immunodeficiency on immunoglobulin replacement therapy. Pediatr Pulmonol. 2019 Feb;54(2):194-199. Indice Impacto: 3,157. Revista en Q1.
PUBMED DOISeasonality and geographical spread of respiratory syncytial virus epidemics in 15 European countries, 2010 to 2016.
Broberg EK, Waris M, Johansen K, Snacken R, Penttinen P; European Influenza Surveillance Network. Seasonality and geographical spread of respiratory syncytial virus epidemics in 15 European countries, 2010 to 2016. Euro Surveill. 2018 Feb;23(5). Indice Impacto: 5,983. Revista en Decil 1
PUBMED DOIHuman Metapneumovirus infections in hospitalized children and comparison with other respiratory viruses in 2005-2014 prospective study.
García-García ML, Calvo C, Rey C, Díaz B, Molinero MD, Pozo F, Casas I. Human Metapneumovirus infections in hospitalized children and comparison with other respiratory viruses in 2005-2014 prospective study. PLoS One. 2017 Mar 16;12(3):e0173504. doi: 10.1371/journal.pone.0173504. eCollection 2017. Indice Impacto: 2,766. Revista en Q1.
PUBMED DOIRespiratory Infections by Enterovirus D68 in Outpatients and Inpatients Spanish Children
Calvo C, Cuevas MT, Pozo F, García-García ML, Molinero M, Calderón A, Gonzalez-Esguevillas M, Pérez-Sautu U, Casas I. Respiratory Infections by Enterovirus D68 in Outpatients and Inpatients Spanish Children. Pediatr Infect Dis J. 2016 Jan;35(1):45-9.
PUBMED DOIClinical and Virologic Characteristics of Early and Moderate Preterm Infants Readmitted with Viral Respiratory Infections.
García-Garcia ML, González-Carrasco E, Quevedo S, Muñoz C, Sánchez-Escudero V, Pozo F, Casas I, Calvo C. Clinical and Virologic Characteristics of Early and Moderate Preterm Infants Readmitted with Viral Respiratory Infections. Pediatr Infect Dis J. 2015 Jul;34(7):693-9. Indice Impacto: 2,587. Revista en Q1
PUBMED DOIEight Year Prospective Study of Adenoviruses Infections in Hospitalized Children. Comparison with Other Respiratory Viruses.
Calvo C, García-García ML, Sanchez-Dehesa R, Román C, Tabares A, Pozo F, Casas I. Eight Year Prospective Study of Adenoviruses Infections in Hospitalized Children. Comparison with Other Respiratory Viruses. PLoS One. 2015 Jul 6;10(7):e0132162. eCollection 2015. Indice Impacto: 3,057. Revista en Q1
PUBMED DOIInfluenza vaccine effectiveness in Spain 2013/14: subtype-specific early estimates using the cycEVA study
Jiménez-Jorge S, Pozo F, de Mateo S, Delgado-Sanz C, Casas I, García-Cenoz M, Castilla J, Sancho R, Etxebarriarteun-Aranzabal L, Quinones C, Martínez E, Vega T, Garcia A, Giménez J, Vanrell JM, Castrillejo D, Larrauri A, on behalf of the Spanish Influenza Sentinel Surveillance System (SISS). Influenza vaccine effectiveness in Spain 2013/14: subtype-specific early estimates using the cycEVA study. Euro Surveill. 2014 Mar 6;19(9). Indice Impacto: 5,722. Revista en Q1.
PUBMED DOIY155H amino acid substitution in influenza A(H1N1)pdm09 viruses does not confer a phenotype of reduced susceptibility to neuraminidase inhibitors
Perez-Sautu U, Pozo F, Cuesta I, Monzon S, Calderon A, Gonzalez M, Molinero M, Lopez-Miragaya I, Rey S, Cañizares A, Rodriguez G, Gonzalez-Velasco C, Lackenby A, Casas I. Y155H amino acid substitution in influenza A(H1N1)pdm09 viruses does not confer a phenotype of reduced susceptibility to neuraminidase inhibitors. Euro Surveill. 2014 Jul 10;19(27):14-20. Indice Impacto: 5,722. Revista en Q1
PUBMED DOICharacterization In Vitro and In Vivo of a Pandemic H1N1 Influenza Virus from a Fatal Case.
Rodriguez A, Falcon A, Cuevas MT, Pozo F, Guerra S, García-Barreno B, Martinez-Orellana P, Pérez-Breña P, Montoya M, Melero JA, Pizarro M, Ortin J, Casas I, Nieto A. Characterization In Vitro and In Vivo of a Pandemic H1N1 Influenza Virus from a Fatal Case. PLoS One. 2013;8(1):e53515. doi: 10.1371/journal.pone.0053515. Epub 2013 Jan 10. Indice Impacto: 3,534. Revista en Q1
PUBMED DOIMycobacterium tuberculosis genotypes and predominant clones among the multidrug-resistant isolates in Spain 1998-2006
3. Samper S, Gavin P, Millan-Lou MI, Iglesias M.J. Jimenez MS. Spanish Working Group on MDR-TB, Covin D, Rastogi N. Mycobacterium tuberculosis genotypes and predominant clones among the multidrug-resistant isolates in Spain 1998-2006. Infec Genet Evol. 2017. Aug 5;55:117.
PUBMED DOIAntitubercular drugs for an old target: GSK693 as a promising inhA direct inhibitor.
5. Martinez-Hoyos M, Perez-Herran E, Gulten G, Encinas L, Alvarez-Gomez D, Alvarez E, Ferrer Bazaga S, Garcia-Perez A, Ortega F, Angulo-Bartures I, Rullas-Trincado J, Blanco Ruano D, Torres P, Castañeda P, Huss S, Fernandez R, Gonzalez del Valle S, Ballel L, Barros D, Modha S, Dhar N, Signorino-Gelo F, McKinney JD, Garcia-Bustos JF, Lavandera JL, Sacchettini JC, Jimenez MS, Martin-Casabona N, Castro-PIchel J, Mendoza-Losana A. Antitubercular drugs for an old target: GSK693 as a promising inhA direct inhibitor. EBioMedicine. 2016; 8:291-301
PUBMED DOIContent with Investigacion .
-
María Cabrerizo Sanz
Tenure Scientist and Group Leader
ORCID code: 0000-0001-7054-5696
Doctor in Chemistry, specializing in Biochemistry and Molecular Biology, Universidad Autónoma de Madrid (2000). Except for a postdoctoral period of 2 years at the Hospital de La Princesa, in which her research was related to onco-hematological diseases, the rest of her scientific career has focused on the study of infectious diseases caused by viruses and their surveillance. She joined the Instituto de Salud Carlos III in 2003, first in the Laboratory of Arbovirus and Imported Viral Diseases, then in the Laboratory of Viral Hepatitis and finally, in the Laboratory of Enterovirus (which is accredited as a National Polio Laboratory -LNP- for the WHO since 1998). She obtained the position of Tenure Scientist in 2016, at the same time she assumed the responsibility of the laboratory, currently of Enteric Viruses: Poliovirus/Enterovirus, Parechovirus and Gastroenteritis-producing Viruses, of the CNM. She has 4 scientific sexennials and 4 quinquennials recognized.
She has been and is PI of 4 consecutive research projects and 3 service contracts, from 2012 to the present, participating, in addition, in other 20 projects. As head of the LNP, she is part of the Working Group of the National Plan for the Eradication of Poliomyelitis and of the WHO European Polio Laboratory Network. She is also a member of the European Non-Polio Enterovirus Network (ENPEN), and of the national cooperation networks CIBERESP and RITIP (IdiPAZ). Since 2023 she is a Council Member from Spain of the European Society.
In total she has published 98 articles in WoS indexed journals (23 Q1 and 22 D1), being first author, senior author or correspondence author in 43 of them (H=27). She has supervised 1 PhD Thesis (2017) and 12 TFM. She is currently supervising another doctoral thesis (IMIENS-UNED). She participates as a teacher in three university masters (UCM, UAH and UV), being coordinator of the subject H2 of the Master of Virology at UCM.
-
Mª Dolores Fernández García
Tenure Scientist
ORCID code: 0000-0003-0336-6596
Degree in Pharmacy (2005) and PhD from the University VII Paris Diderot in Microbiology (2010). She completed her doctoral thesis at the Pasteur Institute in Paris characterizing the molecular and cellular basis of flavivirus entry into cells. Specialist in Public Health Microbiology (European Program EUPHEM coordinated by ECDC). She has worked 3 years for the French Ministry of Foreign Affairs as a researcher at the Pasteur Institute in Dakar (Senegal) carrying out microbiological surveillance activities and research on polioviruses and non-polio enteroviruses in West Africa. She has obtained two Miguel Servet contracts: one to work at IMIBIC in Cordoba (2019) and an intramural one to work at CNM (2020). Both were awarded for the study of neurotropic viruses applying massive sequencing for their diagnosis. In 2021 he joined the CNM-ISCIII as a Tenure Research Scientist at the Enterovirus and Viral Gastroenteritis Unit of the CNM-ISCIII. Since then, she combines her scientific activity with the assistance to the National Health System in the microbiological research of outbreaks and in the Genomic Surveillance of Enteroviruses and Gastroenteritis-producing Viruses.
She is a researcher in the Epidemiology and Public Health Area of the Centro de Investigación Biomédica en Red (CIBERESP-ISCIII). In addition, she is an evaluator and panelist for the HORIZON health program projects of the European Commission, the French National Agency ANRS-Emerging Infectious Diseases, R&D&I in HEALTH of the Strategic Action in Health (ISCIII) and the Andalusian Public Foundation Progreso y Salud. She has worked as scientific advisor to the Spanish Ministry of Health on Rotavirus and Polio. Since 2020 she has been teaching virology in different Spanish universities.
She has worked for WHO in the investigation of numerous outbreaks caused by viruses (Ebola, Zika, Yellow Fever, Dengue, etc.) in African and Asian countries strengthening laboratory capacities through technology transfer of diagnostic methods, training of laboratory personnel in these countries and scientific advisory tasks to the Ministries of Health. She has been the Health Coordinator of the START Project (Spanish Technical Aid Response Team) of the AECID, framed in the “Emergency Medical Teams” initiative of the WHO, participating in the establishment for Spain of a field hospital classified by the WHO as EMT Level 2 for interventions in humanitarian emergencies.
-
Nerea García Ibáñez
Ayudante de Investigación de OPI. Técnico de laboratorio
-
Vanesa Recio Huertas
Ayudante de Investigación de OPI. Técnico de laboratorio (apoyo)
-
Ana Donoso Almenara
Contratada predoctoral pFIS
-
Rubén González Sanz
Técnico Superior Especializado OPI
-
Juan Camacho Padilla
Investigador predoctoral (PFIS)
-
Clara Martín Martín
Investigador predoctoral (PFIS)
-
Nazaret Díaz Sánchez
Técnico Superior Especializado OPI (apoyo)
-
Carmen Serrano Risquez
Investigador predoctoral (CAM)
-
Yasmin Biya Assiry
Técnico de laboratorio en formación (PEJ-CAM)
-
Estrella Ruiz de Pedro
Técnico de laboratorio (PTA para Infraestructuras de I+D+I)
List of staff
Información adicional
The researchers of the Viral Infection and Immunity Unit (UIVI) are part of the CIBER de Infectious Diseases (CIBERINFEC) as an independent group (https://www.ciberinfec.es/grupos/grupo-de-investigacion?id=27501). The UIVI studies the immunopathology of clinically relevant infections in humans, such as chronic viral hepatitis (Hepatitis B, C and D), HIV, and SARS-CoV-2, and their impact on the clinical evolution of infected patients. We also analyse the evolution of the patient after controlling viral replication or after eliminating the virus spontaneously or by antiviral treatment.
The group focuses mainly on translational research in which collaborating clinical groups also participate. On the one hand, ‘omics’ techniques such as genomics, transcriptomics, proteomics, metabolomics, epigenetics and metagenomics are used, which, depending on the type of study, are targeted or not. On the other hand, specific laboratory assays designed in-house, such as PCR, RT-PCR, immunoassays for virus titration and neutralisation, production of monoclonal antibodies, among others, are carried out. With the molecular data obtained from patient samples, we perform bioinformatics/statistical analyses, analysing their association with the clinical condition of the patients and their subsequent evolution.