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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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- 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.

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Publications

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An expanded agar base secreening method for azole resistant Aspergillus fumigatus

Lucio J, Gonzalez-Jimenez I, Garcia-Rubio R, Cuetara MS and Mellado E. Mycoses 2022, 65 (2): 178-185.

PUBMED DOI

Are point mutations in HMG-CoA reductases (Hmg1 and Hmg2) a step towards azole resistance in Aspergillus fumigatus?

Gonzalez-Jimenez I., Lucio J., Roldan A, Alcazar-Fuoli L. and Mellado E. Molecules, 2021, 26(19):5975.

PUBMED DOI

Multi-resistance to non-azole fungicides in Aspergillus fumigatus TR34/L98H azole resistant isolates

Gonzalez-Jimenez I, Garcia-Rubio R, Monzon S, Lucio J, Cuesta I, and Mellado E. Antimicrob Agents Chemother. 17;65(9):e0064221

PUBMED DOI

The sulfur-related metabolic status of Aspergillus fumigatus during infection reveals cytosolic serine hydroxymethyltransferase as a promising antifungal target

Alharthi R, Sueiro-Olivares M, Storer I, Bin Shuraym H, Scott J, Al-Shidhani R, Fortune-Grant R, Bignell E, Tabernero L, Bromley M and Amich J. 2025. Virulence, 16(1):2449075

PUBMED DOI

Guasp, P., E. Lorente, A. Martín-Esteban, E. Barnea, P. Romania, D. Fruci, J. J. W. Kuiper, A. Admon, and J. A. López de Castro. 2019. Redundancy and Complementarity between ERAP1 and ERAP2 Revealed by their Effects on the Behcet's Disease-Associated HLA-B*51 Peptidome. Mol.Cell Proteomics.

Guasp, P., E. Lorente, A. Martín-Esteban, E. Barnea, P. Romania, D. Fruci, J. J. W. Kuiper, A. Admon, and J. A. López de Castro. 2019. Redundancy and Complementarity between ERAP1 and ERAP2 Revealed by their Effects on the Behcet's Disease-Associated HLA-B*51 Peptidome. Mol.Cell Proteomics.

PUBMED DOI

CD69 targeting enhances anti-Vaccinia virus immunity

Notario L., Redondo-Antón J., Alari-Pahissa E., Albentosa A., Leiva M., López D., Sabio G., and Lauzurica P. (2019) CD69 targeting enhances anti-Vaccinia virus immunity. Journal of Virology 12;93(19). pii: e00553-19.

PUBMED DOI

Proteomics analysis reveals that structural proteins of the virion core and involved in gene expression are the main source for HLA class II ligands in vaccinia virus-infected cells.

Lorente, E., Martin-Galiano, A. J., Barnea, E., Barriga, A., Palomo, C., Garcia-Arriaza, J., Mir, C., Lauzurica, P., Esteban, M., Admon, A., and Lopez, D. (2019) Proteomics analysis reveals that structural proteins of the virion core and involved in gene expression are the main source for HLA class II ligands in vaccinia virus-infected cells. J.Proteome.Res. 18(9):3512-3520

PUBMED DOI

Computational characterization of the peptidome in transporter associated with antigen processing (TAP)-deficient cells.

Martin-Galiano, A. J. and Lopez, D. (2019) Computational characterization of the peptidome in transporter associated with antigen processing (TAP)-deficient cells. PLoS.ONE. 14, e0210583.

PUBMED DOI

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