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Viral Pathogenesis and Immunity

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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Hypervirulent Klebsiella pneumoniae: Epidemiology outside Asian countries, antibiotic resistance association, methods of detection and clinical management

12. Hypervirulent Klebsiella pneumoniae: Epidemiology outside Asian countries, antibiotic resistance association, methods of detection and clinical management. Autores: García-Cobos S, Oteo-Iglesias J, Pérez-Vázquez M. Revista: Enferm Infecc Microbiol Clin (Engl Ed). 2025 Feb;43(2):102-109.

PUBMED DOI

Rapid cross-border emergence of NDM-5-producing Escherichia coli in the European Union/European Economic Area, 2012 to June 2022

15. Rapid cross-border emergence of NDM-5-producing Escherichia coli in the European Union/European Economic Area, 2012 to June 2022. Autores: Linkevicius M, Bonnin RA, Alm E, Svartström O, Apfalter P, Hartl R, Hasman H, Roer L, Räisänen K, Dortet L, Pfennigwerth N, Hans JB, Tóth Á, Buzgó L, Cormican M, Delappe N, Monaco M, Giufrè M, Hendrickx AP, Samuelsen Ø, Pöntinen AK, Caniça M, Manageiro V, Oteo-Iglesias J, Pérez-Vázquez M, Westmo K, Mäkitalo B, Palm D, Monnet DL, Kohlenberg A. Revista: Euro Surveill. 2023 May;28(19):2300209.

PUBMED DOI

Characterization of Carbapenemase-Producing Klebsiella oxytoca in Spain, 2016-2017.

18. Characterization of Carbapenemase-Producing Klebsiella oxytoca in Spain, 2016-2017. Autores: Pérez-Vazquez M, Oteo-Iglesias J, Sola-Campoy PJ, Carrizo-Manzoni H, Bautista V, Lara N, Aracil B, Alhambra A, Martínez-Martínez L, Campos J; Spanish Antibiotic Resistance Surveillance Program Collaborating Group. Revista: Antimicrob Agents Chemother. 2019 May 24;63(6): e02529-18.

PUBMED DOI

Carbapenemase-Producing Klebsiella pneumoniae From Transplanted Patients in Brazil: Phylogeny, Resistome, Virulome and Mobile Genetic Elements Harboring blaKPC-2 or blaNDM-1.

16. Carbapenemase-Producing Klebsiella pneumoniae From Transplanted Patients in Brazil: Phylogeny, Resistome, Virulome and Mobile Genetic Elements Harboring blaKPC-2 or blaNDM-1. Autores: Raro OHF, da Silva RMC, Filho EMR, Sukiennik TCT, Stadnik C, Dias CAG, Oteo Iglesias J, Pérez-Vázquez M. Revista: Front Microbiol. 2020 Jul 15;11:1563.

PUBMED DOI

Dissemination of extensively drug-resistant NDM-producing Providencia stuartii in Europe linked to patients transferred from Ukraine, March 2022 to March 2023

17. Dissemination of extensively drug-resistant NDM-producing Providencia stuartii in Europe linked to patients transferred from Ukraine, March 2022 to March 2023. Autores: Witteveen S, Hans JB, Izdebski R, Hasman H, Samuelsen Ø, Dortet L, Pfeifer Y, Delappe N, Oteo-Iglesias J, Żabicka D, Cormican M, Sandfort M, Reichert F, Pöntinen AK, Fischer MA, Verkaik N, Pérez-Vazquez M, Pfennigwerth N, Hammerum AM, Hallstrøm S, Biedrzycka M, Räisänen K, Wielders CC, Urbanowicz P, de Haan A, Westmo K, Landman F, van der Heide HG, Lansu S, Zwittink RD, Notermans DW, Guzek A, Kondratiuk V, Salmanov A, Haller S, Linkevicius M, Gatermann S, Kohlenberg A, Gniadkowski M, Werner G, Hendrickx AP. Revista: Euro Surveill. 2024 Jun;29(23):2300616.

PUBMED DOI

Spread of the FAR-MRSA clone, a fusidic acid- and meticillin-resistant Staphylococcus aureus ST121, Europe, 2014 to 2024.

19. Spread of the FAR-MRSA clone, a fusidic acid- and meticillin-resistant Staphylococcus aureus ST121, Europe, 2014 to 2024. Autores: Roer L, Yin N, Denis O, Vendrik KE, Zwittink RD, Notermans DW, Perrin M, Khonyongwa K, Tristan A, Youenou B, Layer-Nicolaou F, Werner G, Enger H, Eikrem ECH, Darenberg J, Mäkitalo B, Paulsson M, Björkman J, Fang H, Hallbäck ET, Sundqvist M, Lindholm L, Moganeradj K, García-Cobos S, Cañada-García JE, Holzknecht BJ, Eriksen HB, Hoppe M, Bartels MD, Samaniego Castruita JA, Urth TR, Larsen AR, Petersen A. Revista: Euro Surveill. 2025 Jul;30(28):2500452.

DOI

Carbapenemase-producing Emergence of NDM-producing Klebsiella pneumoniae and Escherichia coli in Spain: phylogeny, resistome, virulence and plasmids encoding blaNDM-like genes as determined by WGS. aeruginosa in Spain: interregional dissemination of the high risk-clones ST175 and ST244 carrying blaVIM-2, blaVIM-1, blaIMP-8, blaVIM-20 and blaKPC-2

14. Emergence of NDM-producing Klebsiella pneumoniae and Escherichia coli in Spain: phylogeny, resistome, virulence and plasmids encoding blaNDM-like genes as determined by WGS. Autores: Pérez-Vázquez M, Sola Campoy PJ, Ortega A, Bautista V, Monzón S, Ruiz-Carrascoso G, Mingorance J, González-Barberá EM, Gimeno C, Aracil B, Sáez D, Lara N, Fernández S, González-López JJ, Campos J, Kingsley RA, Dougan G, Oteo-Iglesias J; Spanish NDM Study Group. Revista: J Antimicrob Chemother. 2019 Dec 1;74(12):3489-3496.

PUBMED DOI

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List of staff

Additional Information

The activity of this unit focuses on the development and clinical validation of point-of-care diagnostic methodology against liver viruses based on an emerging field, nanotechnology, a line of research that is developed in collaboration with BioAssays SL. Likewise, this unit focuses on delving into the immuno-virological mechanisms underlying viral infections and coinfections with other microorganisms and their influence on the host through a comprehensive approach to laboratory techniques. 

One of the main lines of research involves the study of the coinfection of viral hepatitis with the Human Immunodeficiency Virus (HIV), evaluating the impact of coinfection and elimination of hepatitis C on the HIV reservoir, as well as its impact on virus-induced senescence, among others through the use of “omic” technologies. 

Our group leads the Multidisciplinary HIV/Hepatitis Coinfection Group (COVIHEP), and maintains collaborations with national and international research groups of excellence, facilitating greater harmonization and quality in the biomedical research carried out. On the other hand, Dr. Briz maintains close collaboration with private companies, promoting intersectoral alliances that represent a competitive advantage.

The activity of this unit focuses on the development and clinical validation of point-of-care diagnostic methodology against liver viruses based on an emerging field, nanotechnology, a line of research that is developed in collaboration with BioAssays SL. Likewise, this unit focuses on delving into the immuno-virological mechanisms underlying viral infections and coinfections with other microorganisms and their influence on the host through a comprehensive approach to laboratory techniques. 

One of the main lines of research involves the study of the coinfection of viral hepatitis with the Human Immunodeficiency Virus (HIV), evaluating the impact of coinfection and elimination of hepatitis C on the HIV reservoir, as well as its impact on virus-induced senescence, among others through the use of “omic” technologies. 

Our group leads the Multidisciplinary HIV/Hepatitis Coinfection Group (COVIHEP), and maintains collaborations with national and international research groups of excellence, facilitating greater harmonization and quality in the biomedical research carried out. On the other hand, Dr. Briz maintains close collaboration with private companies, promoting intersectoral alliances that represent a competitive advantage.

Content with Investigacion Virología Molecular .