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

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

Molecular epidemiology of community-associated methicillin-resistant Staphylococcus aureus in Spain: 2004-12.

Molecular epidemiology of community-associated methicillin-resistant Staphylococcus aureus in Spain: 2004-12. Vindel A, Trincado P, Cuevas O, Ballesteros C, Bouza E, Cercenado E. J Antimicrob Chemother. 2014 Nov;69(11):2913-9.

PUBMED

Draft Genome Sequence of Strain SA_ST125_MupR of Methicillin-Resistant Staphylococcus aureus ST125, a Major Clone in Spain.

Draft Genome Sequence of Strain SA_ST125_MupR of Methicillin-Resistant Staphylococcus aureus ST125, a Major Clone in Spain. Barrado L, Viedma E, Vindel A, Otero JR, Chaves F. Genome Announc. 2013 Aug 8;1(4).

PUBMED

Detection of linezolid-resistant Staphylococcus aureus with 23S rRNA and novel L4 riboprotein mutations in a cystic fibrosis patient in Spain.

Detection of linezolid-resistant Staphylococcus aureus with 23S rRNA and novel L4 riboprotein mutations in a cystic fibrosis patient in Spain. Román F, Roldán C, Trincado P, Ballesteros C, Carazo C, Vindel A. Antimicrob Agents Chemother. 2013 May;57(5):2428-9.

PUBMED

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Additional Information

La inducción de la tolerancia al aloinjerto sigue siendo una meta por alcanzar en el trasplante de órganos. La mayoría de las estrategias terapéuticas se centran en la inhibición del sistema inmunológico adaptativo, pero datos recientes demuestran que el reconocimiento alogénico de las células mieloides inicia el rechazo al trasplante. Terapias dirigidas hacia las células mieloides “in vivo” representan un objetivo potencial para inducir tolerancia inmunológica, pero permanece inexplorado clínicamente.Nuestro laboratorio utiliza una nanoinmunoterapia revolucionaria de nanopartículas de lipoproteínas de alta densidad (HDL) cargadas con rapamicina (mTORi-HDL) que previenen las modificaciones epigenéticas asociadas con la inmunidad entrenada, un estado funcional de los macrófagos recientemente descubierto. Usando un modelo experimental de trasplante en ratón, nuestros resultados demuestran que la administración de esta inmunoterapia con mTORi-HDL previene la respuesta inmunológica y promueve la tolerancia al órgano trasplantado.Nuestro laboratorio muestra un enfoque de investigación multidisciplinar articulado en tres objetivos diferentes para evaluar la relevancia clínica y los efectos terapéuticos de la inmunoterapia como preparación para un ensayo clínico en trasplante de órganos. Los objetivos generales estarán orientados a confirmar la identificación de la inmunidad entrenada como biomarcador y valor analítico para predecir el riesgo de rechazo en pacientes trasplantados bajo tres condiciones: periodos prolongadas de reperfusión isquémica (IRI) (objetivo 1), alosensibilización (objetivo 2) e infección (objetivo 3).

Induction of allograft tolerance remains a goal to be achieved in organ transplantation. Most therapeutic strategies focus on inhibition of the adaptive immune system, but recent data demonstrate that allogeneic recognition of myeloid cells initiates transplant rejection. Therapies targeting myeloid cells “in vivo” represent a potential target to induce immunological tolerance, but remain clinically unexplored. 

Our laboratory uses a revolutionary nanoimmunotherapy of high-density lipoprotein (HDL) nanoparticles loaded with rapamycin (mTORi-HDL) that prevents epigenetic modifications associated with trained immunity, a recently discovered functional state of macrophages. Using an experimental mouse transplant model, our results demonstrate that the administration of this immunotherapy with mTORi-HDL prevents the immune response and promotes tolerance to the transplanted organ. 

Our laboratory shows a multidisciplinary research approach articulated in three different objectives to evaluate the clinical relevance and therapeutic effects of immunotherapy in preparation for a clinical trial in organ transplantation. The general objectives will be aimed at confirming the identification of trained immunity as a biomarker and analytical value to predict the risk of rejection in transplant patients under three conditions: prolonged periods of ischemic reperfusion (IRI) (objective 1), allosensitization (objective 2) and infection (objective 3).

Induction of allograft tolerance remains a goal to be achieved in organ transplantation. Most therapeutic strategies focus on inhibition of the adaptive immune system, but recent data demonstrate that allogeneic recognition of myeloid cells initiates transplant rejection. Therapies targeting myeloid cells “in vivo” represent a potential target to induce immunological tolerance, but remain clinically unexplored. 

Our laboratory uses a revolutionary nanoimmunotherapy of high-density lipoprotein (HDL) nanoparticles loaded with rapamycin (mTORi-HDL) that prevents epigenetic modifications associated with trained immunity, a recently discovered functional state of macrophages. Using an experimental mouse transplant model, our results demonstrate that the administration of this immunotherapy with mTORi-HDL prevents the immune response and promotes tolerance to the transplanted organ. 

Our laboratory shows a multidisciplinary research approach articulated in three different objectives to evaluate the clinical relevance and therapeutic effects of immunotherapy in preparation for a clinical trial in organ transplantation. The general objectives will be aimed at confirming the identification of trained immunity as a biomarker and analytical value to predict the risk of rejection in transplant patients under three conditions: prolonged periods of ischemic reperfusion (IRI) (objective 1), allosensitization (objective 2) and infection (objective 3).

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