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Investigation

Molecular Virology

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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Minilungs from Human Embryonic Stem Cells to Study the Interaction of Streptococcus pneumoniae with the Respiratory Tract

Sempere J, Rossi SA, Chamorro-Herrero I, González-Camacho F, de Lucas MP, Rojas-Cabañeros JM, Taborda CP, Zaragoza Ó, Yuste J, Zambrano A. Minilungs from Human Embryonic Stem Cells to Study the Interaction of Streptococcus pneumoniae with the Respiratory Tract. Microbiol Spectr. 2022 Jun 29;10(3):e0045322

PUBMED DOI

A national longitudinal study evaluating the activity of cefditoren and other antibiotics against non-susceptible Streptococcus pneumoniae strains during the period 2004-20 in Spain

Sempere J, González-Camacho F, Domenech M, Llamosí M, Del Río I, López-Ruiz B, Gimeno M, Coronel P, Yuste J. A national longitudinal study evaluating the activity of cefditoren and other antibiotics against non-susceptible Streptococcus pneumoniae strains during the period 2004-20 in Spain. J Antimicrob Chemother. 2022 Mar 31;77(4):1045-1051.

PUBMED DOI

Nationwide Trends of Invasive Pneumococcal Disease in Spain From 2009 Through 2019 in Children and Adults During the Pneumococcal Conjugate Vaccine Era

de Miguel S, Domenech M, González-Camacho F, Sempere J, Vicioso D, Sanz JC, Comas LG, Ardanuy C, Fenoll A, Yuste J. Nationwide Trends of Invasive Pneumococcal Disease in Spain From 2009 Through 2019 in Children and Adults During the Pneumococcal Conjugate Vaccine Era. Clin Infect Dis. 2021 Dec 6;73(11):e3778-e3787

PUBMED DOI

Pulmonary BCG induces lung-resident macrophage activation and confers long-term protection against tuberculosis

7. Mata E, Tarancón R, Guerrero C, Moreo E, Moreau F, Uranga S, Gomez AB, Marinova D, Domenech M, Gonzalez-Camacho F, Monzon M, Badiola J, Dominguez-Andres J, Yuste J, Anel A, Peixoto A, Martin C, Aguilo N. Pulmonary BCG induces lung-resident macrophage activation and confers long-term protection against tuberculosis. Sci Immunol. 2021 Sep 24;6(63):eabc2934

PUBMED DOI

Vaccination with LytA, LytC, or Pce of Streptococcus pneumoniae Protects against Sepsis by Inducing IgGs That Activate the Complement System

Corsini B, Aguinagalde L, Ruiz S, Domenech M, Yuste J. Vaccination with LytA, LytC, or Pce of Streptococcus pneumoniae Protects against Sepsis by Inducing IgGs That Activate the Complement System. Vaccines. 2021 Feb 23;9(2):186.

PUBMED DOI

Physiologic and transcriptomic effects triggered by overexpression of wild type and mutant DNA topoisomerase I in Streptococcus pneumoniae

García-López M, Hernández P, Megias D, Ferrándiz MJ, de la Campa AG. Int J Mol Sci. 2023; 24:15800.

PUBMED DOI

StaR Is a positive regulator of topoisomerase I activity involved in supercoiling maintenance in Streptococcus pneumoniae

de Vasconcelos Junior AA, Tirado-Vélez JM, Martín-Galiano AJ, Megias D, Ferrándiz MJ, Hernández P, Amblar M, de la Campa AG. Int J Mol Sci. 2023; 24:5973.

PUBMED DOI

Role of PatAB transporter in efflux of levofloxacin in Streptococcus pneumoniae

Amblar M, Zaballos A, de la Campa AG. Antibiotics. 2022; 17:1837.

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