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Investigation

Molecular Virology

Research Lines

Content with Investigacion Virología Molecular .

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

Content with Investigacion Taxonomía Bacteriana .

- Título: Desvelando la genómica de las bacterias anaerobias procedentes de bacteriemias
Referencia Proyecto: PID202-1127477OB-I00-MPY 302/22.
Entidad financiador: Agencia Estatal de Investigación.
Fechas de ejecución: 2023-2026
Financiación 108.900 €.
Investigadora principal: Sylvia Valdezate


 

- Título: Plataformas MALDI-TOF/CMI SENSITITRETM Personal Técnico Apoyo
Referencia: PTA2019-016623-I. 
Entidad Financiadora: Agencia Estatal de Investigación. 
Fechas ejecución 12/2020-11/2023
Investigadora principal: Sylvia Valdezate

- Título: Elementos genéticos móviles protagonistas en la evolución de los serotipos pandémicos M1 y M89 de Streptococcus pyogenes en el síndrome del shock tóxico y otras infecciones invasivas
Referencia: (MPY 377/18).
Entidad financiadora: Instituto de Salud Carlos III. Agencia Estatal de Investigación en Salud Intramural (AESI). 
Fechas de ejecución: 11/2018-12/2022. 
Financiación: 40.000 €.
Investigadoras principales: Pilar Villalón. Co-IP Sylvia Valdezate. 

- Título: Plataformas genéticas y su influencia en la resistencia a co-trimoxazol, macrólidos y tetraciclina en Nocardia spp.
Referencia: MPY 1278/15
Entidad financiadora: Instituto de Salud Carlos III. Agencia Estatal de Investigación en Salud Intramural (AESI).
Fechas de ejecución: 2015-2017.
Financiación: 88.141,8 €. 
Investigadora principal: Sylvia Valdezate

- Título: Filogenia y caracterización de mecanismos moleculares de resistencia en Nocardia spp. 
Referencia: MPY 1446/11
Entidad financiadora: Instituto de Salud Carlos III. Fondo de Investigación Sanitaria (AES). () 
Fechas de ejecución: 04/2012-10/2015
Financiación: 115.457 €. 
Investigadora principal: Sylvia Valdezate.

- Título: Iberian network of laboratories of biological alert. Accreditation of methods for detection highly pathogenic agents (IB-BIOALERTNET). 
Entidad financiadora: COMISIÓN EUROPEA HOME/2012/ISEC/AG/CBRN/4000003810. (Instituto de Salud Carlos III (VISAVET, IVIA, INSA, INIAV))
Referencia: SAFI 1132/13-7. 
Fecha de ejecución: 2013-2015.
Financiación: 699.175 €. 
Tipo de participación: Miembro del equipo investigador.

- Título: EQUATOX Project Establishment of Quality Assurances for theDetection of Biological Toxins of potential Bioterrorism risk. 
Entidad financiadora y convocatoria: Seven Framework Programme for Research FP7-SECURITY. (Robert Koch-Institut Berlin Alemania). 
Referencia: SEC-2011.5.4-1. 
Fechas de ejecución: 2012-2014.

Publications

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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

PUBMED DOI

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.

PUBMED DOI

Content with Investigacion Taxonomía Bacteriana .

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