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HIV Biology and Variability

Líneas de investigación

Content with Investigacion Inmunobiología .

The Immunobiology group has been working for years on the following lines of research:
1) The mechanisms of haematopoietic cell generation throughout ontogeny and the influence that the first haematopoietic cells exert on the innate and adaptive immune system present in the adults. We have identified and characterised a new population of B lymphocytes called B1-Rel (B220lo), which produce high levels of natural IgG/IgA antibodies. We sought to understand their role in the immune response in animal models of infection, analysing their impact on immune cell populations and on the production of soluble mediators (cytokines and immunoglobulins). In this regard, we have evaluated the generation of embryonic megakaryocytes (and their differentiation niches), their functionality and that of platelets, and their influence on haematopoietic development. For lymphoid populations, we have carried out extensive characterisation by flow cytometry and single cell RNA sequencing (scRNAseq) methodology. To carry out these cellomic studies, we have designed complex panels for use in multiparametric phenotypic analysis, and single cell cytometry and RNAseq omics technologies on purified cell populations.


In parallel, we are interested in understanding local immune responses in respiratory infections at times of particular susceptibility due to the fragility of the immune system (childhood and old age), both in mouse animal models, which allow their manipulation, and in humans. 

2) Mouse models studied during neonatal life, in which we evaluated the effect of antibiotic (AB) treatment and addressed the role of TLR receptors in innate, pseudo-innate and adaptive immune cell populations. In these models, we observed that AB administration was able to modulate B-lymphoid populations, as well as their ability to secrete proinflammatory cytokines in culture and their differentiation into plasma cells, with differentiated immunoglobulin repertoires. Furthermore. These effects were mediated through the Toll-like receptor-2 (TLR2).

3) Mouse models with accelerated senescence (SAMP8) and senescent animals (over 20 months of age) to map lymphoid populations and soluble mediators of the immune response (immunoglobulins and cytokines). In these models, the B lymphoid populations (B1Rel and marginal zone B lymphocytes) are observed to be altered, accompanied by an increase in IgG1 with great restriction of their VDJ repertoires.


4) Role of the B1Rel population in animal models of local or systemic infection. We analysed the response to Streptoccoccus pneumoniae (SPN) locally in the lung and systemically in the spleen, as well as the role of TLR4 in these responses.

5) In humans, we are studying immune responses in children with respiratory syncytial virus (RSV) viral primo-infection. In this case we studied the immune response that occurs locally in the nasal mucosa (by analysis of nasal washings, NW) in a cohort of infected children versus healthy controls, stratified by age. We found that lymphomyeloid cells accumulate in these nasal washings in patients with diverse lymphocyte populations, as well as cytokines and immunoglobulins.

6) Analysis and characterisation of extracellular vesicles produced during respiratory infection both in lung supernatants from models of SPN infection and in LN in the case of children with RSV infection.

7) In parallel, we carry out studies of the genetic rearrangements of immunoglobulins and their use in the generation of chimeric receptors for possible use in immunotherapy.

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Publicaciones destacadas

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Invasive Streptococcus pyogenes disease in Spain: a microbiological and epidemiological study covering the period 2007-2019

Villalón P, Sáez-Nieto JA, Rubio-López V, Medina-Pascual MJ, Garrido N, Carrasco G, Pino-Rosa S, Valdezate S. (2021). Invasive Streptococcus pyogenes disease in Spain: a microbiological and epidemiological study covering the period 2007-2019. Eur J Clin Microbiol Infect Dis. 2021 Nov;40(11):2295-2303

PUBMED DOI

Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host-parasite communication.

Eichenberger RM, Talukder MH, Field MA, Wangchuk P, Giacomin P, Loukas A, Sotillo J. Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host-parasite communication. J Extracell Vesicles. 2018 Jan 21;7(1):1428004.

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Genome-wide proximity between RNA polymerase and DNA topoisomerase I supports transcription in Streptococcus pneumoniae

Ferrándiz M-J, Hernández P, de la Campa AG. PLoS Genet. 2021; 17:e1009542.

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TREM1 regulates antifungal immune responses in invasive pulmonary aspergillosis

Bernal-Martinez L, Gonçalves S, de Andres B, Cunha C, Gonzalez Jimenez I, Lagrou K, Mellado E, Gaspar ML, Maertens J, Carvalho A, and Alcazar-Fuoli L. Virulence 2021 Dec;12(1):570-583.

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Guiding the humoral response against HIV-1 toward a MPER adjacent region by immunization with a VLP-formulated antibody-selected envelope variant

Beltran-Pavez C, Ferreira CB, Merino-Mansilla A, Fabra-Garcia A, Casadella M, Noguera-Julian M, Paredes R, Olvera A, Haro I, Brander C, Garcia F, Gatell JM, Yuste E, Sanchez-Merino V; PLoS One. 2018 Dec 19;13(12):e0208345

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The role of methionine synthases in fungal metabolism and virulence

Scott J and Amich J. Essays Biochem (2023) 67 (5): 853-863.

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Global Meningococcal Initiative: Insights on antibiotic resistance, control strategies and advocacy efforts in Western Europe

Borrow R, Campbell H, Caugant DA, Cherkaoui A, Claus H, Deghmane AE, Dinleyici EC, Harrison LH, Hausdorff WP, Bajanca-Lavado P, Levy C, Mattheus W, Mikula-Pratschke C, Mölling P, Sáfadi MA, Smith V, van Sorge NM, Stefanelli P, Taha MK, Toropainen M, Tzanakaki G, Vázquez J. . J Infect. 2024; 89(6): 106335

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Dissociation of actin polymerization and lipid raft accumulation by ligation of the Inducible Costimulator (ICOS, CD278)

6. Y. Acosta, G. Ojeda, M. P. Zafra, I. Seren-Bernardone, A. Sánchez, U. Dianzani, P. Portolés y J. M. Rojo. Dissociation of actin polymerization and lipid raft accumulation by ligation of the Inducible Costimulator (ICOS, CD278). Inmunología, 2012, 31 (1): 4-12.

DOI

Genetic Characterization of Brucella spp.: Whole Genome Sequencing-Based Approach for the Determination of Multiple Locus Variable Number Tandem Repeat Profiles

Pelerito A, Nunes A, Grilo T, Isidro J, Silva C, Ferreira AC, Valdezate S, Núncio MS, Georgi E, Gomes JP. (2021) Genetic Characterization of Brucella spp.: Whole Genome Sequencing-Based Approach for the Determination of Multiple Locus Variable Number Tandem Repeat Profiles. 2021. Front Microbiol. 12;12:740068

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Evaluation of onchocerciasis seroprevalence in Bioko Island (Equatorial Guinea) after years of disease control programmes.

Hernández-González A, Moya L, Perteguer MJ, Herrador Z, Nguema R, Nguema J, Aparicio P, Benito A, Gárate T. Evaluation of onchocerciasis seroprevalence in Bioko Island (Equatorial Guinea) after years of disease control programmes. Parasit Vectors. 2016 Sep 20;9(1):509.

PUBMED DOI

A Small Non-Coding RNA Modulates Expression of Pilus-1 Type in Streptococcus pneumoniae

Acebo P, Herranz C, Bernal-Espenberger L, Gómez-Sanz A, Terron MC, Luque D and Amblar M. Microorganisms. 2021; 9:1883.

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Toll-like receptors in acute kidney injury

Vázquez-Carballo C, Guerrero-Hue M, García Caballero C, Rayego-Mateos S, Opazo-Rios L, Morgado-Pascual JL, Herencia-Bellido C, Vallejo-Mudarra M, Cortegano I, Gaspar ML, de Andrés B, Egido J, Moreno-Gutiérrez JA. Int J Mol Sci. 2021 Jan; 22(2): 816.

PUBMED DOI

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3.

6. CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3. Autores: Cañada-García JE, Moure Z, Sola-Campoy PJ, Delgado-Valverde M, Cano ME, Gijón D, González M, Gracia-Ahufinger I, Larrosa N, Mulet X, Pitart C, Rivera A, Bou G, Calvo J, Cantón R, González-López JJ, Martínez-Martínez L, Navarro F, Oliver A, Palacios-Baena ZR, Pascual Á, Ruiz-Carrascoso G, Vila J, Aracil B, Pérez-Vázquez M, Oteo-Iglesias J; GEMARA/GEIRAS-SEIMC/REIPI CARB-ES-19 Study Group. Revista: Front Microbiol. 2022 Jun 30;13:918362.

DOI

Detection of Broadly Neutralizing Activity within the First Months of HIV-1 Infection

Sanchez-Merino V, Fabra-Garcia A, Gonzalez N, Nicolas D, Merino-Mansilla A, Manzardo C, Ambrosioni J, Schultz A, Meyerhans A, Mascola JR, Gatell JM, Alcami J, Miro JM, Yuste E; J Virol. 2016 May 12;90(11):5231-5245

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Potential implication of azole persistence in the treatment failure of two haematological patients infected with Aspergillus fumigatus

Peláez-García de la Rasilla T, Mato-López A, Pablos-Puertas CE, González-Huerta AJ, Gómez-López A, Mellado E, Amich J. Journal of Fungi, 2023 Jul 30;9(8):805.

PUBMED DOI

Meningococcal disease in the Middle East: A report from the Global Meningococcal Initiative

Al-Abri SS, Abuhasan MY, Albayat SSA, Bai X, Bastaki H, Borrow R, Caugant DA, Dbaibo G, Deghmane AE, Dinleyici EC, Ghuneim N, Sheek-Hussein M, Lucidarme J, Leng S, Koliou MG, Sáfadi MAP, Salman JA, Al-Sanouri T, Smith V, Taha MK, Vázquez J, Wright C, Yezli S. J Infect. 2024; 88(2):71-76.

PUBMED DOI

Complement regulatory protein Crry/p65 costimulation expands natural Treg cells with enhanced suppressive properties in proteoglycan-induced arthritis.

7. Ojeda G., Pini E., Eguiluz C., Montes-Casado M., Broere F., van Eden W., Rojo J.M., and Portolés P. Complement regulatory protein Crry/p65 costimulation expands natural Treg cells with enhanced suppressive properties in proteoglycan-induced arthritis. Arthritis Rheum. 2011 Jun;63(6):1562-72.

PUBMED DOI

Saezia sanguinis gen. nov., sp. nov., a Betaproteobacteria member of order Burkholderiales, isolated from human blood

Medina-Pascual MJ, Monzón S, Villalón P, Cuesta I, González-Romo F, Valdezate S. (2020). Saezia sanguinis gen. nov., sp. nov., a Betaproteobacteria member of order Burkholderiales, isolated from human blood. Int J Syst Evol Microbiol.70:2016-25.

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Changes in protein expression after treatment with Ancylostoma caninum excretory/secretory products in a mouse model of colitis.

Sotillo J, Ferreira I, Potriquet J, Laha T, Navarro S, Loukas A, Mulvenna J. Changes in protein expression after treatment with Ancylostoma caninum excretory/secretory products in a mouse model of colitis. Sci Rep. 2017 Feb 13;7:41883.

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Reactive oxygen species production is a major factor directing the post-antibiotic effect of fluoroquinolones in Streptococcus pneumoniae

García MT, Valenzuela MV, Ferrándiz MJ, de la Campa AG. Antimicrob Agents Chemother. 2019; 63:e00737-19.

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List of staff

Información adicional

The activities of the HIV viral and biology unit (UBVVIH) include research, service to the National Health System (NHS) and the administration of Justice and teaching. Its main lines of research are molecular epidemiology and HIV-1 phylogeny, in which the UBVVIH has carried out numerous national and international collaborations, focusing on the identification of viral genetic forms and the study of their correlations with epidemiological variables. Related lines are phylodynamics and phylogeography, which study the origin and dynamics of growth and spread of HIV-1 variants. Such studies can be used to better understand the evolution of the epidemic and to plan public health actions. 

The UBVHIV also produces and characterises primary isolates and functional clones of the envelope of various genetic forms of HIV-1, which are deposited in repositories and used by numerous international groups. Other lines of research are described in the corresponding section. In terms of service to the NHS, the UBVVIH carries out antiretroviral resistance tests and prediction of tropism as a therapeutic guide in HIV-1 infected patients. As for its collaboration with the Justice Administration, the UBVVIH carries out expert opinions through phylogenetic studies of sequences for legal cases of possible HIV transmissions.

Content with Investigacion Inmunobiología .