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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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PROYECTOS VIGENTES

Título del proyecto: "Vesículas extracelulares y otras moléculas de parásitos para el tratamiento de la enfermedad inflamatoria intestinal: PARATREAT-IBD"

Referencia: Proyecto PID2022-137661OB-I00 (MPY 341/23) financiado por MCIN/AEI /10.13039/501100011033/ y por FEDER Una manera de hacer Europa
Fecha Inicio:    01/12/2023
Fecha Fin:    31/08/2026
Financiación: 162.500 Euros
Investigador principal: Javier Sotillo
Agencia Financiadora: Agencia Estatal de Investigación. MICINN.


 

Título del proyecto: "Desarrollo de nuevos métodos diagnósticos y de seguimiento de la infección por schistosoma haematobium"

Referencia: PI23CIII00034 / MPY 386/23
Fecha Inicio:    01/01/2024
Fecha Fin:    31/12/2026
Financiación: 131.500 Euros
Investigador principal: Javier Sotillo
Agencia Financiadora: Instituto de Salud Carlos III (ISCIII/AESI)

 

Título del proyecto: "Desarrollo de herramientas para el control de la teniosis / cisticercosis en zonas endémicas y vigilancia de las helmintosis humanas emergentes en España"

Referencia: PI22CIII/00010
Fecha Inicio: 01/01/2023
Fecha Fin: 31/12/2025
Financiación: 80.000 Euros
Investigador principal: María Jesús Perteguer
Agencia Financiadora: Instituto de Salud Carlos III (ISCIII/AESI)

 

 

PROYECTOS PASADOS

Título del proyecto: "PERITAS: Molecular epidemiological studies on pathways of transmission and longlasting capacity building to prevent cystic echinococcosis infection."
Coordinador: Adriano Casulli. IP of ISCIII: Maria J. Perteguer.
Entidad financiadora: EULAC Health JOINT CALL on Research and Innovation 016-2017
Periodo: 01/03/2019-31/12/2022.
Cuantía total: 1.083.580 €.

Título del proyecto: "Producción de antígenos y controles positivos recombinantes para el desarrollo y la estandarización de nuevos ensayos serológicos aplicados al diagnóstico y control de helmintosis olvidadas. "
Investigador principal: María Jesús Perteguer.
Entidad financiadora: ISCIII-AESI. Instituto de Salud Carlos III
Periodo: 02/11/2018 - 31/06/2022.
Cuantía total: 78.050 €.

Título del proyecto: "Diagnóstico serológico diferencial de helmintiasis asociadas a eosinofilia: desarrollo de ensayos multianalito (xMAP) con antígenos recombinantes de especies de interés clínico"
Investigador principal: María Jesús Perteguer.
Entidad financiadora: ISCIII-AESI. Instituto de Salud Carlos III
Periodo: 01/01/2015 - 31/12/2018 .
Cuantía total: 91.000 €.

Publications

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Efficacy 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 DOI

Unintended HIV-1 Infection During Analytical Therapy Interruption

Ugarte A, Romero Y, Tricas A, Casado C, Lopez-Galindez C, Garcia F, Leal L. J Infect Dis. 2020 Apr 27,221(10):1740-1742.

PUBMED DOI

Potent 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 DOI

HIV-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

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Viral 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

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Viral 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 DOI

Human Immunodeficiency Virus Type 1 Two-Long Terminal Repeat Circles: A Subject for Debate

Olivares I, Pernas M, Casado C, López-Galindez C. AIDS Rev. 2016 Jan-Mar,18(1):23-31

PUBMED DOI

Improved antibody cross-neutralizing activity in HIV-1 dual double infected LTNP patients.

María Pernas, Concepción Casado, Victor Sanchez-Merino, Alberto Merino-Mansilla, Isabel Olivares, Eloisa Yuste, Cecilio Lopez-Galindez. (2015) PLoS One. Aug 10; 10 (8):e0134054

PUBMED DOI

Contribution 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 DOI

Prevalence 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 DOI

A 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 DOI

Characterizing the antiviral effect of an ATR inhibitor on human immunodeficiency virus type 1 replication

Docando F, Casado C, Pernas M, Mota-Biosca A, López-Galíndez C, Olivares I. Arch Virol. 2020 Mar, 165(3):683-690

PUBMED DOI

HIV-1 Dual Infected LTNP-EC Patients Developed an Unexpected Antibody Cross-Neutralizing Activity

Pernas M, Sanchez-Merino V, Casado C, Merino-Mansilla A, Olivares I, Yuste E, Lopez-Galindez C. PLoS One. 2015 Aug 10,10(8): e0134054

PUBMED DOI

Factors 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

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Elite controllers and lessons learned for HIV-1 cure

Lopez-Galindez C, Pernas M, Casado C, Olivares I, Lorenzo-Redondo R. Curr Opin Virol. 2019 Oct, 38:31-36

PUBMED DOI

Viruses from a cluster of HIV-1 Elite controllers inherit viral characteristics associated with the clinical non-progressor phenotype

Casado C, Marrero-Hernández S, Márquez-Arce D, Pernas M, Marfil S, Borràs-Grañana F, Olivares I, Cabrera-Rodríguez R, Valera M-S, de Armas-Rillo L, Lemey P, Blanco J, Valenzuela-Fernández A, Lopez-Galíndez C. 2018. mBio 9:e02338-17.

PUBMED DOI

Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure

Casado C, Galvez C, Pernas M, Tarancon-Diez L, Rodriguez C, Sanchez-Merino V, Vera M, Olivares I, De Pablo-Bernal R, Merino-Mansilla A, Del Romero J, Lorenzo-Redondo R, Ruiz-Mateos E, Salgado M, Martinez-Picado J, Lopez-Galindez C. Sci Rep. 2020 Feb 5,10(1):1902

PUBMED DOI

High-Risk Sexual Practices Contribute to HIV-1 Double Infection Among Men Who Have Sex with Men in Madrid

Casado C, Pernas M, Rava M, Ayerdi O, Vera M, Alenda R, Jiménez P, Docando F, Olivares I, Zaballos A, Vicario JL, Rodríguez C, Del Romero J, Lopez-Galindez C. AIDS Res Hum Retroviruses. 2020 Nov, 36(11):896-904

PUBMED DOI

Identification of a Spanish HIV-1 Long Term Non-Progressor cluster infected with a low replicating virus

Concepción Casado, Maria Pernas, Virginia Sandonis, Tamara Alvaro-Cifuentes, Isabel Olivares, Rosa Fuentes, Lorena Martínez Prats, Eulalia Grau, Lidia Ruiz, Rafael Delgado, Carmen Rodríguez, Jorge del Romero, and Cecilio López-Galíndez. (2013). PLoS One. 8 (10):e77663.

PUBMED DOI

Evidence of Ongoing Replication in a Human Immunodeficiency Virus Type 1 Persistently Infected Cell Line

Isabel Olivares, Carmen Sánchez-Jiménez, Catarina Reis Vieira, Víctor Toledano, Mónica Gutiérrez-Rivas, and Cecilio López-Galíndez. Journal of General Virology. 94, 944-954.

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