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Cellular Immunology

Líneas de investigación

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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:

  • Diagnosis and reference of HIV infection (types 1 and 2) through detection of specific antibodies and detection of proviral DNA by PCR.

  • 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.

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Publicaciones destacadas

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Emergence of linezolid-resistant coagulase-negative staphylococci in an intensive care unit

2. Emergence of linezolid-resistant coagulase-negative staphylococci in an intensive care unit. Balandin B, Lobo B, Orden B, Román F, García E, Martínez R, Valdivia M, Ortega A, Fernández I, Galdos P. Infect Dis (Lond). 2016;48(5):343-9.

PUBMED DOI

Horizontal gene transmission of the cfr gene to MRSA and Enterococcus: role of Staphylococcus epidermidis as a reservoir and alternative pathway for the spread of linezolid resistance.

3. Horizontal gene transmission of the cfr gene to MRSA and Enterococcus: role of Staphylococcus epidermidis as a reservoir and alternative pathway for the spread of linezolid resistance. Cafini F, Nguyen le TT, Higashide M, Román F, Prieto J, Morikawa K. J Antimicrob Chemother. 2016 Mar;71(3):587-92.

PUBMED DOI

Emergence of cfr-Mediated Linezolid Resistance in a Methicillin-Resistant Staphylococcus aureus Epidemic Clone Isolated from Patients with Cystic Fibrosis.

4. Emergence of cfr-Mediated Linezolid Resistance in a Methicillin-Resistant Staphylococcus aureus Epidemic Clone Isolated from Patients with Cystic Fibrosis. de Dios Caballero J, Pastor MD, Vindel A, Máiz L, Yagüe G, Salvador C, Cobo M, Morosini MI, del Campo R, Cantón R; GEIFQ Study Group. Antimicrob Agents Chemother. 2015 Dec 14;60(3):1878-82.

PUBMED DOI

The dynamic changes of dominant clones of Staphylococcus aureus causing bloodstream infections in the European region: results of a second structured survey.

5. The dynamic changes of dominant clones of Staphylococcus aureus causing bloodstream infections in the European region: results of a second structured survey. Grundmann H, Schouls LM, Aanensen DM, Pluister GN, Tami A, Chlebowicz M, Glasner C, Sabat AJ, Weist K, Heuer O, Friedrich AW; ESCMID Study Group on Molecular Epidemiological Markers; European Staphylococcal Reference Laboratory Working Group. Euro Surveill. 2014 Dec 11;19(49).

PUBMED DOI

Peptidoglycan recycling contributes to intrinsic resistance to fosfomycin in Acinetobacter baumannii.

6. Gil-Marqués ML, Moreno-Martínez P, Costas C, Pachón J, Blázquez J, McConnell M.J.* Peptidoglycan recycling contributes to intrinsic resistance to fosfomycin in Acinetobacter baumannii. Journal of Antimicrobial Chemotherapy. 2018 Nov 1;73(11):2960-2968.

PUBMED DOI

Immunization with lipopolysaccharide-free outer membrane complexes protects against Acinetobacter baumannii infection.

7. Pulido MR, García-Quintanilla M, Pachón J, McConnell M.J.* Immunization with lipopolysaccharide-free outer membrane complexes protects against Acinetobacter baumannii infection. Vaccine. 2018 Jul 5;36(29):4153-4156.

PUBMED DOI

Inhibition of LpxC increases antibiotic susceptibility in Acinetobacter baumannii.

8. García-Quintanilla M, Caro-Vega JM, Pulido MR, Moreno-Martínez P, Pachón J, McConnell M.J.* Inhibition of LpxC increases antibiotic susceptibility in Acinetobacter baumannii. Antimicrobial Agents and Chemotherapy. 2016 Jul 22;60(8):5076-9.

PUBMED DOI

Immunization with lipopolysaccharide-deficient whole cells provides protective immunity in an experimental mouse model of Acinetobacter baumannii infection.

9. García-Quintanilla M., Pulido M.R., Pachón J. and McConnell, M.J.* Immunization with lipopolysaccharide-deficient whole cells provides protective immunity in an experimental mouse model of Acinetobacter baumannii infection. PLOS One. 2014 Dec 8;9(12).

PUBMED DOI

Varicella-zoster virus clades circulating in Spain over two decades.

I. González; A. Molina-Ortega; P. Pérez-Romero; J.E. Echevarría; L. He; D. Tarragó. Varicella-zoster virus clades circulating in Spain over two decades. Journal of Clinical Virology. 110, pp. 17- 21. 2019.

PUBMED DOI

Human herpesvirus 8-associated inflammatory cytokine syndrome.

M. Prieto-Barrios; R. Aragón-Miguel; D. Tarragó-Asensio; A. Lalueza; C. Zarco-Olivo. Human herpesvirus 8-associated inflammatory cytokine syndrome. JAMA Dermatology. 154 - 2, pp. 228 - 230. 2018.

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Encephalitis associated with human herpesvirus-7 infection in an immunocompetent adult.

M. Parra; A. Alcala; C. Amoros; A. Baeza; A. Galiana; D. Tarragó; M.Á. García-Quesada; V. Sánchez-Hellín. Encephalitis associated with human herpesvirus-7 infection in an immunocompetent adult. Virology Journal. 14 - 1, 2017.

PUBMED DOI

Molecular epidemiology of enterovirus and parechovirus infections according to patient age over a 4-year period in Spain.

M. Cabrerizo; M. Díaz-Cerio; C. Muñoz-Almagro; N. Rabella; D. Tarragó; M.P. Romero; M.J. Pena; C. Calvo; S. Rey-Cao; A. Moreno-Docón; I. Martínez-Rienda; A. Otero; G. Trallero. Molecular epidemiology of enterovirus and parechovirus infections according to patient age over a 4-year period in Spain. J Med Virol. 2017 Mar;89(3):435-442.

PUBMED DOI

Viral epidemic outbreaks and public health alerts studied at the National Centre of Microbiology during a two-year period (2012-2013).

J.M. Echevarría Mayo; A.A. Avellón Calvo; M. Cabrerizo Sanz; I. Casas Flecha; J.E. Echevarría Mayo; Fd.eO. de Ory Manchón; A. Negredo Antón; F. Pozo Sánchez; M.P. Sánchez-Seco Fariñas; D. Tarragó Asensio; G. Trallero Masó. Viral epidemic outbreaks and public health alerts studied at the National Centre of Microbiology during a two-year period (2012-2013). Revista española de salud pública. 90, pp. E16 - E16. 2016

PUBMED

Application of a commercial immunoblot to define EBV IgG seroprofiles.

F. de Ory; E. Guisasola; D. Tarragó; J.C. Sanz. Application of a commercial immunoblot to define EBV IgG seroprofiles. Journal of Clinical Laboratory Analysis. 29 - 1, pp. 47 - 51. 2015.

PUBMED DOI

Molecular epidemiology of enterovirus 71, coxsackievirus A16 and A6 associated with hand, foot and mouth disease in Spain.

M. Cabrerizo; D. Tarragó; C. Muñoz-Almagro; E. del Amo; M. Domínguez-Gil; J.M.-S. Eiros; I. López-Miragaya; C. Pérez; J. Reina; A. Otero; I. González; J.E. Echevarría; G. Trallero. Molecular epidemiology of enterovirus 71, coxsackievirus A16 and A6 associated with hand, foot and mouth disease in Spain. Clinical Microbiology and Infection. 20 - 3, pp. O150 - O156. 2014.

PUBMED DOI

Molecular epidemiology of the first Spanish enterovirus A71 outbreak associated with severe neurological diseases, 2016.

R Gonzalez-Sanz*, D Casas-Alba, C Launes, C Muñoz-Almagro, M Ruiz-García, MJ Gonzalez-Abad, M Alonso, G Megias, N Rabella, M del Cuerpo, M Gozalo-Margüello, A González-Praetorius, A Martínez-Sapiña, MJ Goyanes-Galán, MP Romero, C Calvo, A Antón, M Imaz, M Aranzamendi, Á Hernandez, A Moreno-Docón, S Rey Cao, A Navascuences, A Otero, M Cabrerizo. Molecular epidemiology of the first Spanish enterovirus A71 outbreak associated with severe neurological diseases, 2016. Euro Surveill. 2019 Feb;24(7).

PUBMED DOI

Acute flaccid paralysis (AFP) surveillance: challenges and opportunities from 18 years’ experience, Spain, 1998 to 2015.

J Masa-Calles, N Torner, N López-Perea, MV Torres de Mier, B Fernández-Martínez, M Cabrerizo, V Gallardo-García, C Malo, M Margolles, M Portell, N Abadía, A Blasco, S García-Hernández, H Marcos, N Rabella, C Marín, A Fuentes, I Losada, A Nieto, V García Ortúzar, M García Cenoz, JM Arteagoitia, Á Blanco Martínez, A Rivas, D Castrillejo, Spanish AFP Surveillance Working Group. Acute flaccid paralysis (AFP) surveillance: challenges and opportunities from 18 years’ experience, Spain, 1998 to 2015. EuroSurveill 2018 23(47):pii=1700423.

PUBMED DOI

Recommendations for enterovirus diagnostics and characterisation within and beyond Europe.

H Harvala, E Broberg, K Benschop, N Berginc, S Ladhani, P Susi, C Christiansen, J McKenna, D Allen, P Makiello, G McAllister, M Carmen, M Sveinsdottir, K Zakikhany, T Gunnarsdottir, R Dyrdak, X Nielsen, T Madsen, J Paul, C Moore, K von Eije, A Piralla , M Strutt, M Carileir, L Vanoverschelde, R Poelman, A Anton, X López-Labrador, C Galli, K Keeren, M Maier, H Cassidy, S Derdas, C Savolainen-Kopra, S Diedrich, S Nordbø, P Minor, J Buesa, H Yu, Q Liao, JL Bailly, F Baldanti, A MacAdam, N Grossly, A Mirand, S Dudman, I Schuffenecker, S Kadamba, n Neyts, M Griffiths, J Richter, C Margaretto, S Govind, U Morley, S Krokstad, J Dean, M Salort, B Prochazka, H-R Honkanen, M Cabrerizo, M Majumdar, L Pellegrinelli, G Nebbia, M Wiewel, S Cottrell, P Coyle, O Adams, J Martin, S Midgley, P Horby, K Wolthers, B Hubert Niesters, P Simmonds and TK Fischer. Recommendations for enterovirus diagnostics and characterisation within and beyond Europe. J Clin Virol 101: 11-17 (2018).

PUBMED DOI

Molecular surveillance of norovirus, 2005-16: an epidemiological analysis of data collected from the NoroNet network.

4. J van Beek, M de Graaf, H Al-Hhello, DJ Allen, K Ambert-Balay, N Botteldoorn, M Brytting, J Buesa, M Cabrerizo, M Chan, F Cloak, I Di Bartolo, S Guix, J Hewitt, N Iritani, M Jin, R Johne, I Lederer, J Mans, V Martella, L Maunula, G McAllister, S Niendorf, HG Niesters, AT Podkolzin, M Poljsak-Prijatelj, L Dam Rasmussen, G Reuter, G Tuite, A Kroneman, H Vennema, MPG Koopmans, on behalf of NoroNet. Molecular surveillance of norovirus, 2005-16: an epidemiological analysis of data collected from the NoroNet network. Lancet Infect Dis 18:545-553 (2018)

PUBMED DOI

First Cases of Severe Flaccid Paralysis Associated with Enterovirus D68 Infection in Spain, 2015-2016.

M Cabrerizo*, JP García-Iñiguez, F Munell, A Amado, P Madurga-Revilla, C Rodrigo, S Pérez, A Martínez-Sapiña, A Antón, G Suárez, N Rabella, V Del Campo, A Otero, J Masa-Calles. First Cases of Severe Flaccid Paralysis Associated with Enterovirus D68 Infection in Spain, 2015-2016. Pediatric Infect Dis J; 36: 1214-1216 (2017).

PUBMED DOI

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List of staff

Información adicional

Our current objective is the analysis of costimulatory molecules that modulate lymphocyte activation and the adaptive and innate immune response; specifically the inducible costimulator ICOS and its association with the enzyme phosphatidylinositol-3-kinase (PI3K). ICOS is induced in T lymphocytes and some innate immune cells; It is involved in normal and pathological immune responses and in inflammation regulatory circuits. Its signals are mediated by the association of PI3K, enzymes that regulate many aspects of the response to antigen, lymphoproliferative syndromes, lupus and cancer. 

We analyzed the usefulness of ICOS, its ligand (ICOS-L) and the PI3K associated with ICOS as therapeutic targets in immune response to infections and tumors and in autoimmune diseases. We used two different approaches: i) pharmacological (effect of PI3K p110 isoform inhibitors on immune response) and ii) genetic (analysis of mouse models with tissue-specific conditioned modification of PI3K p110α). We study; 1) The role of PI3K-p110α in the activation and differentiation of cells involved in innate and adaptive immune response to infection, tumors and autoimmunity, seeking new therapies. 2) The functional consequences of costimulation by ICOS/ICOS-L and its mediators, in innate immune cells that simultaneously express ICOS and its ligand.

Content with Investigacion Virología Molecular .