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Microbial Immunology and Immunogenetics

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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Epidemiology of the Acinetobacter-derived cephalosporinase, carbapenem-hydrolysing oxacillinase and metallo-beta-lactamase genes, and of common insertion sequences, in epidemic clones of Acinetobacter baumannii from Spain

Villalón P, Valdezate S, Medina-Pascual MJ, Carrasco G, Vindel A, Saez-Nieto JA. Epidemiology of the Acinetobacter-derived cephalosporinase, carbapenem-hydrolysing oxacillinase and metallo-beta-lactamase genes, and of common insertion sequences, in epidemic clones of Acinetobacter baumannii from Spain. J Antimicrob Chemother. 2013;68(3):550-3.

PUBMED DOI

Shortcomings of the commercial MALDI-TOF MS database and use of MLSA as an arbiter in the identification of Nocardia species

Carrasco G, de Dios Caballero J, Garrido N, Valdezate S, Cantón R, Sáez-Nieto JA. Shortcomings of the commercial MALDI-TOF MS database and use of MLSA as an arbiter in the identification of Nocardia species. Front Microbiol. 2016 21;7:542.

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Kinetics of the invasion and egress processes of Babesia divergens, observed by time-lapse video microscopy.

Sevilla E; González LM; Luque D; Gray J; Montero E. 2018. Kinetics of the invasion and egress processes of Babesia divergens, observed by time-lapse video microscopy. Scientific Reports. 8:14116.DOI: 10.1038/s41598-018-32349-7

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Misdiagnosis of Babesiosis as Malaria, Equatorial Guinea, 2014.

2. Arsuaga M; González LM; Salvador Padial E; Woubshet Dinkessa A; Sevilla E; Trigo E; Puente S; Gray J; Montero E. 2018. Misdiagnosis of Babesiosis as Malaria, Equatorial Guinea, 2014. Emerging Infectious Diseases.24-8, pp.1588-1589.

PUBMED DOI

A fatal case of Babesia divergens infection in Northwestern Spain

3. Asensi V; González LM; Fernández-Suárez J; Sevilla E; Navascués RÁ; Suárez ML; Lauret ME; Bernardo A; Carton JA; Montero E. 2018. A fatal case of Babesia divergens infection in Northwestern Spain. Ticks Tick Borne Dis.9-3, pp.730-734.

PUBMED DOI

First report of Babesia microti-caused babesiosis in Spain.

Arsuaga M*; Gonzalez LM*; Lobo CA; Calle F; Bautista JM; Azcárate IG; Puente S; Montero E. 2016. First report of Babesia microti-caused babesiosis in Spain. Vector Borne Zoonotic Dis.16-10, pp.677-679. (*)= contribuyeron igualmente en este trabajo.

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First record of Babesia sp. in Antarctic penguins.

5. Montero E; González LM; Chaparro A; Benzal J; Bertellotti M; Masero JA; Colominas-Ciuró R; Vidal V; Barbosa A. 2016. First record of Babesia sp. in Antarctic penguins. Ticks Tick Borne Dis.7-3, pp.498-501.

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Ultrastructure of the Babesia divergens free merozoite

6. Del Carmen Terrón M; González-Camacho F; González LM; Luque D; Montero E. 2016. Ultrastructure of the Babesia divergens free merozoite.Ticks Tick Borne Dis.7-6, pp.1274-1279.

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First report of Babesia divergens infection in an HIV patient

7. González LM; Castro E; Lobo CA; Richart A; Ramiro R; González-Camacho F; Luque D; Velasco AC; Montero E. 2015. First report of Babesia divergens infection in an HIV patient. Int J Infect Dis. 33:202-4.

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Severe babesiosis in immunocompetent man, Spain

9. González LM, Rojo S, González-Camacho F, Luque D, Lobo CA, Montero E. 2014. Severe babesiosis in immunocompetent man, Spain. Emerging Infectious Disease. 20(4):724-726.

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The efficacy of the ultraviolet C pathogen inactivation system in the reduction of Babesia divergens in pooled buffy coat platelets

Castro E, González LM, Rubio JM, Ramiro R, Gironés N, Montero E. 2014. The efficacy of the ultraviolet C pathogen inactivation system in the reduction of Babesia divergens in pooled buffy coat platelets. Transfusion. 54(9): 2207-2216.

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Pneumoviridae fusion proteins as immunogens to induce cross-neutralizing antibody responses

Olmedillas E, Cano O, Martinez I, Luque D, Terron MC, McLellan JS, et al. Chimeric Pneumoviridae fusion proteins as immunogens to induce cross-neutralizing antibody responses. EMBO Mol Med. 2018;10(2):175-87.

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Ultrastructure of the Babesia divergens free merozoite

Terrón M.C, González-Camacho F., González L.M., Luque D.*, Montero E. 2016. Ultrastructure of the Babesia divergens free merozoite. Ticks Tick Borne Diseases. 7(6):1274-1279. *Corresponding author. IF: 3.23, Q1.

PUBMED DOI

High-Quality Draft Genome of Babesia divergens, the Etiological Agent of Cattle and Human Babesiosis.

8. Cuesta I; González LM; Estrada K; Grande R; Zaballos A; Lobo CA; Barrera J; Sanchez-Flores A; Montero E. 2014. High-Quality Draft Genome of Babesia divergens, the Etiological Agent of Cattle and Human Babesiosis. Genome Announcement. 2: e01194-14.

PUBMED DOI

Horizontal gene transmission of the cfr gene to MRSA and Enterococcus: role of Staphylococcus epidermidis as a reservoir and alternative pathway for the spread of linezolid resistance.

Horizontal gene transmission of the cfr gene to MRSA and Enterococcus: role of Staphylococcus epidermidis as a reservoir and alternative pathway for the spread of linezolid resistance. Cafini F, Nguyen le TT, Higashide M, Román F, Prieto J, Morikawa K. J Antimicrob Chemother. 2016 Mar;71(3):587-92.

PUBMED

Emergence of linezolid-resistant coagulase-negative staphylococci in an intensive care unit.

Emergence of linezolid-resistant coagulase-negative staphylococci in an intensive care unit. Balandin B, Lobo B, Orden B, Román F, García E, Martínez R, Valdivia M, Ortega A, Fernández I, Galdos P. Infect Dis (Lond). 2016;48(5):343-9.

PUBMED

Clinical, microbiological, and molecular characterization of pediatric invasive infections by Streptococcus pyogenes in Spain in a context of global outbreak

Ramírez de Arellano E, Saavedra-Lozano J, Villalón P, Jové-Blanco A, Grandioso D, Sotelo J, Gamell A, González-López JJ, Cervantes E, Gónzalez MJ, Rello-Saltor V, Esteva C, Sanz-Santaeufemia F, Yagüe G, Manzanares Á, Brañas P, Ruiz de Gopegui E, Carrasco-Colom J, García F, Cercenado E, Mellado I, Del Castillo E, Pérez-Vazquez M, Oteo-Iglesias J, Calvo C; Spanish PedGAS-Net/CIBERINFEC GAS Study Group. Clinical, microbiological, and molecular characterization of pediatric invasive infections by Streptococcus pyogenes in Spain in a context of global outbreak. mSphere. 2024 Mar 26;9(3):e0072923

PUBMED DOI

Co-occurrence of the cephalosporinase cepA and carbapenemase cfiA genes in a Bacteroides fragilis division II strain, an unexpected finding

Valdezate S, Medina-Pascual MJ, Villalón P, Garrido N, Monzón S, Cuesta I, Cobo F (2024). Co-occurrence of the cephalosporinase cepA and carbapenemase cfiA genes in a Bacteroides fragilis division II strain, an unexpected finding. J Antimicrobial Chem. 2024 Jul 1;79(7):1683-1687

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Exploring the genetic background of the botulism neurotoxin BoNT/B2 in Spain

Valdezate S, Carrasco G, Medina MJ, Garrido N, Del Pino S, Valiente M, Pallarés MP, Villalon P. (2023). Exploring the genetic background of the botulism neurotoxin BoNT/B2 in Spain. Microbiol Spectr. Sep 26;11(5):e0238023

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Focusing on Gordonia Infections: Distribution, Antimicrobial Susceptibilities and Phylogeny

Pino-Rosa S, Medina-Pascual MJ, Carrasco G, Garrido N, Villalón P, Valiente M, Valdezate S. (2023). Focusing on Gordonia Infections: Distribution, Antimicrobial Susceptibilities and Phylogeny. Antibiotics (Basel). 26;12(11):1568

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