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Investigation

Arbovirus and imported viral diseases

Research Lines

Content with Investigacion Inmunopatología del SIDA .

Research Lines:

1.    Molecular mechanisms associated to the protection of HIV-1 infection in limb-girdle muscular dystrophy dominant D2 (LGMDD2) patients.
2.    Generation of neutralizing antibodies for therapeutic use based on the broad-spectrum neutralizing response against founder viruses.
3.    Characterization of the immune memory against SARS-CoV-2 in a population over 65 years of age.
4.    Screening and characterization of new anti-latency drugs against HIV-1.
5.    Study of viral entry and HIV tropism in viruses of special epidemiological relevance in Spain. 
6.    Genetic mechanisms of protection and control of HIV-1 infection in populations with extreme phenotypes.

Clinical studies:

1.    Phase 1 clinical trial to evaluate the safety and immunogenicity of HIV-1 envelope-based 763SIP8/MPLA-5 vaccine as a preventive vaccine in healthy uninfected adults. 
2.    ENE-COVID-Senior: Prospective observational study in a cohort of elderly nursing home residents to establish their immune status after receiving a complete vaccination regimen.

Implementation of new technologies:

1.    Identification of HIV-1 integration sites by deep sequencing.
2.    Single cell transcriptomics with simultaneous TCR/BCR sequencing.
3.    Epidemiological intelligence for prediction of SARS-CoV-2 variants likely to emerge in different vaccination settings.
 

Research projects

Content with Investigacion Inmunopatología del SIDA .

1.    Immune response to SARS-CoV-2 infection: effect in naïve vaccinees and seropositives against the most transmissible variants and relevance of host genetics.
Principal Investigator: Javier García Pérez. 
Funding Agency: Acción Estratégica en Salud Intramural 2021(ISCIII)
Funding: 135.000 €
Duration: 2022-2025. 
Project Reference: PI21CIII/00025.
2.    Design and generation of viral stocks of new SARS-CoV-2 variants (omicron subvariants) and analysis of their susceptibility to antibodies neutralization.
Principal Investigator: Javier García Pérez.
Funding Agency: Hipra Scientific S.L.U.
Funding: 103.771 €
Duration: 2023-2025.
Project Reference: MVP 198/23.
3.    Characterization of a mutation in transportin 3 that protects against HIV infection: molecular mechanisms and discovery of new drugs.
Principal Investigator: José Alcamí y Javier García Pérez.
Funding Agency:     Proyectos de I+D+I, Generación de Conocimiento y Retos Investigación de la Agencia Estatal de Investigación.
Funding: 240.000 €
Duration: 2022-2026. 
Project Reference: PID2021-125978OB-C21 funded by MICIU/AEI/10.13039/501100011033 and by FEDER, UE

4.    Generation of immunogens based on HIV-1 envelopes from acutely infected individuals with a broad neutralizing response against founder viruses.
Principal investigator: Nuria González Fernández.
Funding Agency: Acción Estratégica en Salud Intramural 2023 (ISCIII)
Funding: 82.000 €
Duration: 2024-2026. 
Project Reference: PI23CIII/00039.
5.    Phase 1 clinical trial to evaluate the safety and immunogenicity of HIV-1 envelope-based 763SIP8/MPLA-5 vaccine. 
Principal Investigator: Josep Mallolas Masferrer.
Funding Agency: Proyectos de Investigación Clínica Independiente, Acción Estratégica en Salud 2021-2023 (ISCIII).
Funding: 173.200 €
Duration: 2024-2026. 
Project Reference: ICI23/00025.
6.    Service of immunological determinations of the ENE-COVID SENIOR II protocol.
Principal Investigator: Mayte Pérez Olmeda y Javier García Pérez. 
Funding Agency: Fundación para la investigación biomédica del Hospital Universitario La Paz
Funding: 185.037 €
Duration: 2024-2025. 
Project Reference: MOTR 219/24.
7.    Characterization of the immune memory against SARS-CoV-2 in a population over 65 years of age using single cell transcriptomics.
Principal Investigator: Javier García Pérez y Francisco Díez Fuertes.
Funding Agency: Acción Estratégica en Salud Intramural 2021(ISCIII)
Funding: 152.000 €
Duration: 2025-2027. 
Project Reference: PI24CIII/00058
8. Evaluation of rimonabant and cannbinooid analogues in HIV infection and viral latency.
Principal Investigator: Luis Miguel Bedoya del Olmo. 
Funding Agency: Universidad Complutense de Madrid
Funding: 12.000 €
Duration: 2024-2025. 
Project Reference: PR12/24-31553.
9. Discovery of new inhibitors of HIV-1 RNA biogenesis based on blocking the ribonucleoprotein RRE-Rev.
Principal Investigator: José Gallego Sala. Associate Researcher: Luis Miguel Bedoya del Olmo
Funding Agency: Department of Innovation, Universities, Science and Digital Society. Generalitat Valenciana.
Funding: 543,683.84 €
Duration: 2025-2027. 
Project Reference: PROMETEO/2021/036.

Publications

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HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients

Brochado-Kith; Martínez I; Berenguer J; et al; Fernández-Rodríguez A (AC); Resino S. (11/12). 2021. HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients. Journal of Biomedical Sciences. Springer Nature. 28-1.

DOI

OLFM4 polymorphisms predict septic shock survival after major surgery. Eur J Clin Invest.

Pérez-García F; Resino S; Gómez-Sánchez E; et al; Jiménez-Sousa MÁ (10/10). OLFM4 polymorphisms predict septic shock survival after major surgery. Eur J Clin Invest. 2021. 51(4):e13416. doi: 10.1111/eci.13416.

Alcazar-Fuoli L, Mellado E, Garcia-Effron G, Buitrago MJ, Lopez JF, Grimalt JO, Cuenca-Estrella JM, Rodriguez-Tudela JL. Aspergillus fumigatus C-5 sterol desaturases Erg3A and Erg3B: role in sterol biosynthesis and antifungal drug susceptibility. Antimicrob Agents Chemother. 2006 Feb

Alcazar-Fuoli L, Mellado E, Garcia-Effron G, Buitrago MJ, Lopez JF, Grimalt JO, Cuenca-Estrella JM, Rodriguez-Tudela JL. Aspergillus fumigatus C-5 sterol desaturases Erg3A and Erg3B: role in sterol biosynthesis and antifungal drug susceptibility. Antimicrob Agents Chemother. 2006 Feb;50(2):453-60. doi: 10.1128/AAC.50.2.453-460.2006. PMID: 16436696; PMCID: PMC1366924.

PUBMED

14. Alcazar-Fuoli L, Mellado E, Alastruey-Izquierdo A, Cuenca-Estrella M, Rodriguez-Tudela JL. Aspergillus section Fumigati: antifungal susceptibility patterns and sequence-based identification. Antimicrob Agents Chemother. 2008 Apr

Alcazar-Fuoli L, Mellado E, Alastruey-Izquierdo A, Cuenca-Estrella M, Rodriguez-Tudela JL. Aspergillus section Fumigati: antifungal susceptibility patterns and sequence-based identification. Antimicrob Agents Chemother. 2008 Apr;52(4):1244-51. doi: 10.1128/AAC.00942-07. Epub 2008 Jan 22. PMID: 18212093; PMCID: PMC2292508.

PUBMED DOI

Alcazar-Fuoli L, Mellado E, Alastruey-Izquierdo A, Cuenca-Estrella M, Rodriguez-Tudela JL. Species identification and antifungal susceptibility patterns of species belonging to Aspergillus section Nigri. Antimicrob Agents Chemother. 2009 Oct

Alcazar-Fuoli L, Mellado E, Alastruey-Izquierdo A, Cuenca-Estrella M, Rodriguez-Tudela JL. Species identification and antifungal susceptibility patterns of species belonging to Aspergillus section Nigri. Antimicrob Agents Chemother. 2009 Oct;53(10):4514-7. doi: 10.1128/AAC.00585-09. Epub 2009 Jul 27. PMID: 19635955; PMCID: PMC2764190.

PUBMED DOI

Alcazar-Fuoli L, Mellado E, Cuenca-Estrella M, Sanglard D. Probing the role of point mutations in the cyp51A gene from Aspergillus fumigatus in the model yeast Saccharomyces cerevisiae. Med Mycol. 2011 Apr

Alcazar-Fuoli L, Mellado E, Cuenca-Estrella M, Sanglard D. Probing the role of point mutations in the cyp51A gene from Aspergillus fumigatus in the model yeast Saccharomyces cerevisiae. Med Mycol. 2011 Apr;49(3):276-84. doi: 10.3109/13693786.2010.512926. Epub 2010 Sep 10. PMID: 20831364.

PUBMED DOI

Alcazar-Fuoli L, Cuesta I, Rodriguez-Tudela JL, Cuenca-Estrella M, Sanglard D, Mellado E. Three-dimensional models of 14α-sterol demethylase (Cyp51A) from Aspergillus lentulus and Aspergillus fumigatus: an insight into differences in voriconazole interaction. Int J Antimicrob Agents. 2011 Nov

Alcazar-Fuoli L, Cuesta I, Rodriguez-Tudela JL, Cuenca-Estrella M, Sanglard D, Mellado E. Three-dimensional models of 14α-sterol demethylase (Cyp51A) from Aspergillus lentulus and Aspergillus fumigatus: an insight into differences in voriconazole interaction. Int J Antimicrob Agents. 2011 Nov;38(5):426-34. doi: 10.1016/j.ijantimicag.2011.06.005. Epub 2011 Aug 25. PMID: 21871783.

PUBMED DOI

Alcazar-Fuoli L, Mellado E. Ergosterol biosynthesis in Aspergillus fumigatus: its relevance as an antifungal target and role in antifungal drug resistance.

Alcazar-Fuoli L, Mellado E. Ergosterol biosynthesis in Aspergillus fumigatus: its relevance as an antifungal target and role in antifungal drug resistance. Front Microbiol. 2013 Jan 10;3:439. doi: 10.3389/fmicb.2012.00439. PMID: 23335918; PMCID: PMC3541703.

PUBMED DOI

Bernal-Martínez L, Alcazar Fuoli L, Miguel-Revilla B, Carvalho A, Cuétara Garcia MS, Garcia-Rodriguez J, Cunha C, Gómez-García de la Pedrosa E, Gomez-Lopez A. High-Resolution Melting Assay for Genotyping Variants of the CYP2C19 Enzyme and Predicting Voriconazole Effectiveness. Antimicrob Agents Chemother. 2019 May 24

Bernal-Martínez L, Alcazar Fuoli L, Miguel-Revilla B, Carvalho A, Cuétara Garcia MS, Garcia-Rodriguez J, Cunha C, Gómez-García de la Pedrosa E, Gomez-Lopez A. High-Resolution Melting Assay for Genotyping Variants of the CYP2C19 Enzyme and Predicting Voriconazole Effectiveness. Antimicrob Agents Chemother. 2019 May 24;63(6):e02399-18. doi: 10.1128/AAC.02399-18. PMID: 30910893; PMCID:PMC6535561.

PUBMED DOI

Lupiañez CB, Martínez-Bueno M, Sánchez-Maldonado JM, Badiola J, Cunha C, Springer J, Lackner M, Segura-Catena J, Canet LM, Alcazar-Fuoli L, López-Nevot MA, Fianchi L, Aguado JM, Pagano L, López-Fernández E, Alarcón-Riquelme M, Potenza L, Gonçalves SM, Luppi M, Moratalla L, Solano C, Sampedro A, González-Sierra P, Cuenca-Estrella M, Lagrou K, Maertens JA, Lass-Flörl C, Einsele H, Vazquez L; PCRAGA Study Group, Loeffler J, Ríos-Tamayo R, Carvalho A, Jurado M, Sainz J. Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis. Infect Immun. 2020 Mar 23

Lupiañez CB, Martínez-Bueno M, Sánchez-Maldonado JM, Badiola J, Cunha C, Springer J, Lackner M, Segura-Catena J, Canet LM, Alcazar-Fuoli L, López-Nevot MA, Fianchi L, Aguado JM, Pagano L, López-Fernández E, Alarcón-Riquelme M, Potenza L, Gonçalves SM, Luppi M, Moratalla L, Solano C, Sampedro A, González-Sierra P, Cuenca-Estrella M, Lagrou K, Maertens JA, Lass-Flörl C, Einsele H, Vazquez L; PCRAGA Study Group, Loeffler J, Ríos-Tamayo R, Carvalho A, Jurado M, Sainz J. Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis. Infect Immun. 2020 Mar 23;88(4):e00882-19. doi: 10.1128/IAI.00882-19. PMID: 31964743; PMCID: PMC7093133.

PUBMED DOI

Are Reduced Levels of Coagulation Proteins Upon Admission Linked to COVID-19 Severity and Mortality? Front Med (Laussane).

Ceballos FC; Ryan P; Blancas R; et al; Jiménez-Sousa MÁ (20/20). Are Reduced Levels of Coagulation Proteins Upon Admission Linked to COVID-19 Severity and Mortality? Front Med (Laussane). 2021; 8:718053. PMID: 34660629. doi: 10.3389/fmed.2021.718053.

T allele was linked to non-AIDS progression in ART-naïve HIV-infected patients: a retrospective study.

Jiménez-Sousa MA; Jiménez JL; Bellón JM; et al (1/10). CYP27B1 rs10877012 T allele was linked to non-AIDS progression in ART-naïve HIV-infected patients: a retrospective study. J Acquir Immune Defic Syndr 2020 ;85(5):659-664. doi: 10.1097/QAI.0000000000002485.

PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients

Salguero, Sergio; Brochado-Kith, Oscar; Verdices, Ana Virseda; et al; Jiménez-Sousa María A (‡, AC); Resino, Salvador (‡, AC). (12/12). 2023. PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study. Biomedicine & pharmacotherapy. 159, pp.114220. ISSN 1950-6007.

Relative telomere length impact on mortality of COVID-19: Sex differences.Journal of medical virology.

Virseda-Berdices, Ana; Concostrina-Martinez, Leyre; Martinez-Gonzalez, Oscar; et al; Fernandez-Rodriguez, Amanda (‡), Jiménez-Sousa María A (‡). (14/14). 2023. Relative telomere length impact on mortality of COVID-19: Sex differences.Journal of medical virology. 95-1, pp.e28368. ISSN 1096-9071.

Plasma miRNA profile at COVID-19 onset predicts severity status and mortality.

Fernandez-Pato, Asier; Virseda-Berdices, Ana; Resino, Salvador; et al; Jiménez-Sousa María A (‡, AC); Fernandez-Rodriguez, Amanda (‡). (20/20). 2022. Plasma miRNA profile at COVID-19 onset predicts severity status and mortality. EMERGING MICROBES & INFECTIONS. 11(1):676-688. doi: 10.1080/22221751.2022.2038021.

Blood microbiome is associated with changes in portal hypertension after successful direct-acting antiviral therapy in patients with HCV-related cirrhosis.The Journal of antimicrobial chemotherapy.

Virseda-Berdices, Ana; Brochado-Kith, Oscar; Diez, Cristina; et al; Jimenez-Sousa, Maria Angeles. (16/16). 2021. Blood microbiome is associated with changes in portal hypertension after successful direct-acting antiviral therapy in patients with HCV-related cirrhosis.The Journal of antimicrobial chemotherapy. 77(3):719-726. doi: 10.1093/jac/dkab444. ISSN 1460-2091.

Chronic pulmonary aspergillosis update: A year in review. Med Mycol. 2019 Apr 1

Barac A, Kosmidis C, Alastruey-Izquierdo A, Salzer HJF; CPAnet. Chronic pulmonary aspergillosis update: A year in review. Med Mycol. 2019 Apr 1;57(Supplement_2):S104-S109. doi: 10.1093/mmy/myy070. PMID: 30816975.

PUBMED DOI

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

Content with Investigacion Inmunopatología del SIDA .

List of staff

Additional Information

Our objectives are research into well-established autochthonous viruses (Toscana, West Nile and Lymphocoriomeningitis), imported viruses with a vector in Spain (mainly Zika, Dengue and Chikungunya), and viruses that cause haemorrhagic fevers (such as Ebola, Lassa or Crimea Congo, which despite being autochthonous, we include in this category) without forgetting other viruses that, at any time, may become emerging viruses and cause public health alerts.

The group's main research objective is to identify and characterise the aforementioned viruses that cause disease and those circulating in our environment with pathogenic potential.

One of the cross-cutting objectives of the laboratory is to optimise methods for the detection of these viruses and their application to determine the incidence, prevalence and/or presence of the viruses in our environment.

However, in addition to methodological development, it is important to know the origin of the circulating viruses, their antigenic relationships with related viruses, the pathogenicity of the different isolates or the interactions of the agents with their host both in cell culture and in arthropod vectors when this is possible. The aim is to strengthen our role as a National Reference Laboratory for zoonoses through research.

Our objectives are research into well-established autochthonous viruses (Toscana, West Nile and Lymphocoriomeningitis), imported viruses with a vector in Spain (mainly Zika, Dengue and Chikungunya), and viruses that cause haemorrhagic fevers (such as Ebola, Lassa or Crimea Congo, which despite being autochthonous, we include in this category) without forgetting other viruses that, at any time, may become emerging viruses and cause public health alerts.

The group's main research objective is to identify and characterise the aforementioned viruses that cause disease and those circulating in our environment with pathogenic potential.

One of the cross-cutting objectives of the laboratory is to optimise methods for the detection of these viruses and their application to determine the incidence, prevalence and/or presence of the viruses in our environment.

However, in addition to methodological development, it is important to know the origin of the circulating viruses, their antigenic relationships with related viruses, the pathogenicity of the different isolates or the interactions of the agents with their host both in cell culture and in arthropod vectors when this is possible. The aim is to strengthen our role as a National Reference Laboratory for zoonoses through research.

Content with Investigacion Inmunopatología del SIDA .