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Microbial Immunology and Immunogenetics

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:

  • 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.

Research projects

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Publications

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Nrf2 plays a protective role against intravascular hemolysis-mediated acute kidney injury.

Rubio-Navarro A, Vázquez-Carballo C, Guerrero-Hue M, García-Caballero C, Herencia C, Gutierrez E, Yuste C, Sevillano A, Praga M, Egea J, Cannata P, Cortegano I, de Andrés B, Gaspar ML, Cadenas S, Michalska P, León R, Ortiz, A, Egido J, Moreno JA. Front Pharmacol. 2019; 10: 740.

PUBMED DOI

ICOS deficiency hampers the homeostasis, development and activity of NK cell

Montes-Casado M, Ojeda G, Aragoneses-Fenoll L, López D, de Andrés B, Gaspar ML, Dianzani U, Rojo JM, Portolés P. PLoS One 2019 Jul 8;14(7):e0219449.

PUBMED DOI

Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance

Braza MS, Conde P, García M, Cortegano I, Brahmachary M, Pothula V, Fay F, Boros P, Werner SA, Ginhoux F, Mulder WJM, Ochando J. Am J Transplant 2018 May;18(5):1247-1255.

PUBMED DOI

CD45 expression discriminates waves of embryonic megakaryocytes in the mouse.

Cortegano, I., Serrano, N., Ruiz, C., Rodríguez, M., Prado, C., Alía, M., Hidalgo, A., Cano, E., de Andrés B. and Gaspar, ML. 2018. Haematologica, 104(9):1853-1865

PUBMED DOI

Podocytes as new cellular targets of hemoglobin toxicity in massive intravascular hemolysis.

Rubio-Navarro A, Sanchez-Niño MD, Guerrero-Hue M, García-Caballero C, Gutiérrez E, Yuste C, Sevillano A, Praga M, Egea J, Román E, Cannata P, Ortega R, Cortegano I, de Andrés B, Gaspar ML, Cadenas S, Ortiz A, Egido J, Moreno JA. Podocytes as new cellular targets of hemoglobin toxicity in massive intravascular hemolysis. 2018. J.Pathol. 244(3):296-310.

PUBMED DOI

Spatially-restricted JAG1-Notch signaling in the human thymus provides permissive microenvironments for dendritic cell development.

Martín Gayo, E., González-García, S., García-León, M., Murcia-Ceballos, A., Alcain, J., García-Peydró, M., Allende, L., de Andrés, B., Gaspar, ML. and Toribio, ML. J.Exp.Med. (2017) 214:3361-3379

PUBMED DOI

Altered Marginal Zone and innate-like B cells in aged SAMP8 mice with defective IgG1 responses

Cortegano, I., Rodriguez, M., Martin, I., Prado, C., Ruiz, C., Hortigüela, R., Alia, M., Vilar, M., Mira, H., Cano, E., de Andrés, B., and Gaspar, ML. Cell death & disease (2017) 8, e3000

PUBMED DOI

The formation of titan cells in Cryptococcus neoformans depends on the mouse strain and correlates with induction of Th2-type responses

García-Barbazán, I., Trevijano-Contador, N., Rueda, C., de Andrés, B., Pérez-Tavárez, R., Herrero-Fernández, I., Gaspar ML., and Zaragoza, O. Cellular Microbiology (2015) 18:111-124

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