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Immune Presentation and Regulation

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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Laursen CB, Davidsen JR, Van Acker L, Salzer HJF, Seidel D, Cornely OA, Hoenigl M, Alastruey-Izquierdo A, Hennequin C, Godet C, Barac A, Flick H, Munteanu O, Van Braeckel E. CPAnet Registry-An International Chronic Pulmonary Aspergillosis Registry. J Fungi (Basel). 2020 Jun

Laursen CB, Davidsen JR, Van Acker L, Salzer HJF, Seidel D, Cornely OA, Hoenigl M, Alastruey-Izquierdo A, Hennequin C, Godet C, Barac A, Flick H, Munteanu O, Van Braeckel E. CPAnet Registry-An International Chronic Pulmonary Aspergillosis Registry. J Fungi (Basel). 2020 Jun 29;6(3):E96. doi: 10.3390/jof6030096. PMID: 32610566.

PUBMED DOI

Project from GEMICOMED (SEIMC) and REIPI. Molecular identification and susceptibility testing of molds isolated in a Prospective Surveillance of Triazole Resistance in Spain (FILPOP2 study). Antimicrob Agents Chemother. 2018 Jun

Alastruey-Izquierdo A*, Alcazar-Fuoli L, Rivero-Menéndez O, Ayats J, Castro C, García-Rodríguez J, Goterris-Bonet L, Ibáñez-Martínez E, Linares-Sicilia MJ, Martin-Gomez MT, Martín-Mazuelos E, Pelaez T, Peman J, Rezusta A, Rojo S, Tejero R, Vicente Anza D, Viñuelas J, Zapico MS, Cuenca-Estrella M; members of the FILPOP2 Project from GEMICOMED (SEIMC) and REIPI. Molecular identification and susceptibility testing of molds isolated in a Prospective Surveillance of Triazole Resistance in Spain (FILPOP2 study). Antimicrob Agents Chemother. 2018 Jun 25. doi: 10.1128/AAC.00358-18. PMID: 29941643.

PUBMED DOI

In vitro activity of APX001A against rare moulds using EUCAST and CLSI methodologies. J Antimicrob Chemother. 2019 May 1

Rivero-Menendez O, Cuenca-Estrella M, Alastruey-Izquierdo A.* In vitro activity of APX001A against rare moulds using EUCAST and CLSI methodologies. J Antimicrob Chemother. 2019 May 1;74(5):1295-1299. doi: 10.1093/jac/dkz022. PMID: 30753499.

PUBMED DOI

In vitro activity of olorofim (F901318) against clinical isolates of cryptic species of Aspergillus by EUCAST and CLSI methodologies. J Antimicrob Chemother. 2019 Jun 1

Rivero-Menendez O, Cuenca-Estrella M, Alastruey-Izquierdo A.* In vitro activity of olorofim (F901318) against clinical isolates of cryptic species of Aspergillus by EUCAST and CLSI methodologies. J Antimicrob Chemother. 2019 Jun 1;74(6):1586-1590. doi: 10.1093/jac/dkz078. PMID: 30891600.

PUBMED DOI

Molecular Identification, Antifungal Susceptibility Testing, and Mechanisms of Azole Resistance in Aspergillus Species Received within a Surveillance Program on Antifungal Resistance in Spain. Antimicrob Agents Chemother. 2019 Aug 23

Rivero-Menendez O, Soto-Debran JC, Medina N, Lucio J, Mellado E, Alastruey-Izquierdo A*. Molecular Identification, Antifungal Susceptibility Testing, and Mechanisms of Azole Resistance in Aspergillus Species Received within a Surveillance Program on Antifungal Resistance in Spain. Antimicrob Agents Chemother. 2019 Aug 23;63(9). doi: 10.1128/AAC.00865-19. PMID: 31285229.

PUBMED DOI

Clinical and Laboratory Development of Echinocandin Resistance in Candida glabrata: Molecular Characterization. Front Microbiol. 2019 Jul 11

Rivero-Menendez O, Navarro-Rodriguez P, Bernal-Martinez L, Martin-Cano G, Lopez-Perez L, Sanchez-Romero I, Perez-Ayala A, Capilla J, Zaragoza O, Alastruey-Izquierdo A*. Clinical and Laboratory Development of Echinocandin Resistance in Candida glabrata: Molecular Characterization. Front Microbiol. 2019 Jul 11;10:1585. doi: 10.3389/fmicb.2019.01585. PMID: 31354675.

PUBMED DOI

In vitro activity of olorofim against clinical isolates of Scedosporium species and Lomentospora prolificans using EUCAST and CLSI methodologies. J Antimicrob Chemother. 2020 Aug 28

Rivero-Menendez O, Cuenca-Estrella M, Alastruey-Izquierdo A.* In vitro activity of olorofim against clinical isolates of Scedosporium species and Lomentospora prolificans using EUCAST and CLSI methodologies. J Antimicrob Chemother. 2020 Aug 28. doi: 10.1093/jac/dkaa351. PMID:32856079.

PUBMED DOI

Early innate immune response triggered by the human respiratory syncytial virus and its regulation by ubiquitination/deubiquitination processes.

Martín-Vicente M*, Resino S#, Martínez I#*. Early innate immune response triggered by the human respiratory syncytial virus and its regulation by ubiquitination/deubiquitination processes. J Biomed Sci. 2022 Feb 13;29(1):11. doi: 10.1186/s12929-022-00793-3. PMID: 35152905 (R; FI= 12.771; D1 Medicine, Research & Experimental; JCR 2021).

PUBMED

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List of staff

Additional Information

El grupo está interesado en el estudio de la respuesta inmune desde una perspectiva multidisciplinar que incluye aproximaciones genómicas, bioquímicas, proteómicas, modelos in vivo y biotecnológicas encaminadas al diseño de estrategias terapéuticas frente a diversas enfermedades crónicas, infecciosas y raras que poseen un claro componente inmunológico en su etiología. Los objetivos concretos actuales se centran en: Presentación antigénica: Identificación de las reglas de presentación antigénica para su aplicación en el diseño tratamientos terapéuticos incluyendo vacunas. Estudio de la función CD69 y su regulación; su uso como diana terapéutica en la movilización de precursores hematopoyéticos y en la potenciación de la respuesta inmune mediada por CD69 con en la potenciación de vacunas utilizando como vector el virus vaccinia.

The group is interested in the study of the immune response from a multidisciplinary perspective that includes genomic, biochemical, proteomic, in vivo and biotechnological models aimed at the design of therapeutic strategies against various chronic, infectious and rare diseases that have a clear immunological component in their etiology.


The current specific objectives focus on:

 

  • Antigenic presentation: Identification of antigenic presentation rules for their application in the design of therapeutic treatments including vaccines.
  • Study of CD69 function and its regulation; its use as a therapeutic target in the mobilization of hematopoietic precursors and in the potentiation of the immune response mediated by CD69 with the potentiation of vaccines using the vaccinia virus as a vector.

The group is interested in the study of the immune response from a multidisciplinary perspective that includes genomic, biochemical, proteomic, in vivo and biotechnological models aimed at the design of therapeutic strategies against various chronic, infectious and rare diseases that have a clear immunological component in their etiology.


The current specific objectives focus on:

 

  • Antigenic presentation: Identification of antigenic presentation rules for their application in the design of therapeutic treatments including vaccines.
  • Study of CD69 function and its regulation; its use as a therapeutic target in the mobilization of hematopoietic precursors and in the potentiation of the immune response mediated by CD69 with the potentiation of vaccines using the vaccinia virus as a vector.

Content with Investigacion Virología Molecular .