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Investigación

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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Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients.

12. Martin-Vicente M#, Almansa R#, Martínez I#, Tedim AP, Bustamante E, Tamayo L, Aldecoa C, Gómez JM, Renedo G, Berezo JÁ, Cedeño JA, Mamolar N, García Olivares P, Herrán-Monge R, Cicuendez R, Enríquez P, Ortega A, Jorge N, Doncel C, de la Fuente A, Bustamante-Munguira J, Muñoz-Gómez MJ, González-Rivera M, Puertas C, Más V, Vázquez M, Pérez-García F, Rico-Feijoo J, Martín S, Motos A, Fernandez-Barat L, Eiros JM, Dominguez-Gil M, Ferrer R, Barbé F, Trapiello W, Kelvin DJ, Bermejo-Martin JF, Resino S, Torres A. Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients. J Intern Med. 2022 Feb; 291(2):232-240. doi: 10.1111/joim.13386. PMID: 34611927 (A; FI= 13.068; D1 Medicine, General & Internal; JCR 2021).

PUBMED

Strategies Targeting the Innate Immune Response for the Treatment of Hepatitis C Virus-Associated Liver Fibrosis.

13. Sepulveda-Crespo D, Resino S*, Martinez I*. Strategies Targeting the Innate Immune Response for the Treatment of Hepatitis C Virus-Associated Liver Fibrosis. Drugs. 2021 Drugs. 2021 Mar; 81(4):419-443. doi: 10.1007/s40265-020-01458-x. PMID: 33400242. (R; FI= 11.431; D1 Pharmacology & Pharmacy; JCR 2021).

PUBMED

Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation FRONTIERS IN IMMUNOLOGY.

3 Ceballos, Francisco C.; Virseda-Berdices, Ana; Resino, Salvador; et al; Jimenez-Sousa, Maria Angeles. (19/19). 2022. Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation FRONTIERS IN IMMUNOLOGY. ISSN 1664-3224.

Metabolomic changes after DAAs therapy are related to the improvement of cirrhosis and inflammation in HIV/HCV-coinfected patients.

4 Virseda-Berdices, Ana; Rojo, David; Martinez, Isidoro; et al; Jimenez-Sousa, Maria Angeles. (14/14). 2022. Metabolomic changes after DAAs therapy are related to the improvement of cirrhosis and inflammation in HIV/HCV-coinfected patients. BIOMEDICINE & PHARMACOTHERAPY. 147:112623. ISSN 1950-6007.

HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients FRONTIERS IN IMMUNOLOGY.

7 Brochado-Kith, Oscar; Martinez, Isidoro; Berenguer, Juan; et al; Jiménez-Sousa, Maria Angeles (‡, AC); Resino, Salvador (‡, AC). (13/13). 2021. HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients FRONTIERS IN IMMUNOLOGY. 12:723196. ISSN 1664-3224.

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

3. Fernández-Pato A; Virseda-Berdices A; Resino S; et al; Fernández-Rodríguez A (AC). (20/20). 2022. Plasma miRNA profile at COVID-19 onset predicts severity status and mortality Emerging Microbes and Infections. Taylor & Francis Online. ISSN 2222-1751.

DOI

Diagnostic Performance of the HCV Core Antigen Test To Identify Hepatitis C in HIV-Infected Patients: a Systematic Review and Meta-Analysis

4. Sepúlveda-Crespo D; Treviño-Nakoura A; Bellon JM; Jiménez-Sousa MA; Ryan P; Martínez I; Fernández-Rodríguez A (AC); Resino S. (7/8). 2022. Diagnostic Performance of the HCV Core Antigen Test To Identify Hepatitis C in HIV-Infected Patients: a Systematic Review and Meta-Analysis.Journal of clinical microbiology. pp.e0133122. ISSN 0095-1137.

DOI

Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation

6. Ceballos FC; Virseda-Berdices A; Resino S; et al; Jiménez-Sousa MÁ (AC). (19/19). 2022. Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation.Frontiers in immunology. 13, pp.925558. WOS (78)

DOI

Novel genes and sex differences in COVID-19 severity

7. Cruz R; Almeida SD; Heredia ML; et al; Fernández-Rodríguez A; Carracedo Á. (51/168). 2022. Novel genes and sex differences in COVID-19 severity. Human molecular genetics. ISSN 0964-6906.

DOI

Different HCV Exposure Drives Specific miRNA Profile in PBMCs of HIV Patients

8. Valle-Millares D; Brochado-Kith O; Martín-Carbonero L; et al; Fernández-Rodríguez A (AC). (22/22). 2021. Different HCV exposure drives specific miRNA profile in PBMCs of HIV patients Biomedicines. MDPI. 9-11, pp.1627.

DOI

Are Reduced Levels of Coagulation Proteins Upon Admission Linked to COVID-19 Severity and Mortality?

9. Ceballos F; Ryan P; Blancas R; et al; Fernández-Rodríguez A (AC); Jiménez-Sousa MA. (19/20). 2021. Are Reduced Levels of Coagulation Proteins Upon Admission Linked to COVID-19 Severity and Mortality? Frontiers in Medicine. Frontiers. 8-718053.

DOI

Telomere Length Increase in HIV/HCV-Coinfected Patients with Cirrhosis after HCV Eradication with Direct-Acting Antivirals

12 . Molina-Carrión S; Brochado-Kith, Oscar; González-García J; et al; Angeles Jimenez-Sousa, Maria. (16/16). 2020. Telomere length increase in HIV/HCV-coinfected patients with cirrhosis after HCV eradication with direct acting antivirals. JOURNAL OF CLINICAL MEDICINE. MDPI. ISSN 2077-0383.

DOI

MicroRNA Profile of HCV Spontaneous Clarified Individuals, Denotes Previous HCV Infection

15. Brochado-Kith, Oscar; Gomez-Sanz, Alicia; Real LM; et al; Fernandez-Rodriguez, Amanda (AC). (16/16). 2019. MicroRNA Profile of HCV Spontaneous Clarified Individuals, Denotes Previous HCV Infection JOURNAL OF CLINICAL MEDICINE. MDPI. 7. ISSN 2077-0383.

DOI

​​Persistent Immunity against SARS-CoV-2 in Individuals with Oncohematological Diseases Who Underwent Autologous or Allogeneic Stem Cell Transplantation after Vaccination

​​Persistent Immunity against SARS-CoV-2 in Individuals with Oncohematological Diseases Who Underwent Autologous or Allogeneic Stem Cell Transplantation after Vaccination. Rodríguez-Mora S, Pérez-Lamas L, Solera Sainero M, Torres M, Sánchez-Menéndez C, Corona M, Mateos E, Casado-Fernández G, Alcamí J, García-Pérez J, Pérez-Olmeda M, Murciano-Antón A, López-Jiménez J, García-Gutiérrez V, Coiras M (AC). Cancers 2023, 15(8), 2344. doi: 10.3390/cancers15082344. PMID: 37190272.

PUBMED DOI

Sustained Cytotoxic Response of Peripheral Blood Mononuclear Cells from Unvaccinated Individuals Admitted to the ICU Due to Critical COVID-19 Is Essential to Avoid a Fatal Outcome

Sustained Cytotoxic Response of Peripheral Blood Mononuclear Cells from Unvaccinated Individuals Admitted to the ICU Due to Critical COVID-19 Is Essential to Avoid a Fatal Outcome. Casado-Fernández G, Corona M, Torres M, Saez AJ, Ramos-Martín F, Manzanares M, Vigón L, Mateos E, Pozo F, Casas I, García-Gutierrez V, Rodríguez-Mora S, Coiras M (AC). Int J Environ Res Public Health. 2023 Jan20;20(3):1947. doi: 10.3390/ijerph20031947. PMID: 36767310.

PUBMED DOI

Dasatinib: effects on the macrophage phospho proteome with a focus on SAMHD1 and HIV-1 infection

Dasatinib: effects on the macrophage phospho proteome with a focus on SAMHD1 and HIV-1 infection. Williams ESCP, Szaniawski MA, Martins LJ, Innis EA, Alcamí J, Hanley TM, Spivak AM, Coiras M, Planelles V. Clin Res HIV AIDS.2022;8(1):1053. https://pubmed.ncbi.nlm.nih.gov/36589263/. PMID: 36589263.

PUBMED

Early Cellular and Humoral Responses Developed in Oncohematological Patients after Vaccination with One Dose against COVID-19

Early Cellular and Humoral Responses Developed in Oncohematological Patients after Vaccination with One Dose against COVID-19. Rodríguez-Mora S, Corona M, Torres M, Casado-Fernández G, García-Pérez J, Ramos-Martín F, Vigón L, Manzanares M, Mateos E, Martín-Moro F, Zurdo-Castronuño A, Murciano-Antón MA, Alcamí J, Pérez-Olmeda M, López-Jiménez J, García-Gutiérrez V, Coiras M (AC). J Clin Med. 2022 May 16;11(10):2803. doi: 10.3390/jcm11102803. PMID: 35628927.

PUBMED DOI

Changes in the immune response against SARS-CoV-2 in individuals with severe COVID-19 treated with high dose of vitamin D

Changes in the immune response against SARS-CoV-2 in individuals with severe COVID-19 treated with high dose of vitamin D. Torres M, Casado G, Vigón L, Rodríguez-Mora S, Mateos E, Ramos-Martín F, López-Wolf D, Sanz-Moreno J, Ryan-Murua P, Taboada-Martínez ML, López-Huertas MR, Cervero M, Coiras M (AC). Biomed Pharmacother. 2022 Apr 14;150:112965. doi: 10.1016/j.biopha.2022.112965. PMID: 35468580.

PUBMED DOI

Strong Cellular Immune Response, but Not Humoral, against SARS-CoV-2 in Oncohematological Patients with Autologous Stem Cell Transplantation after Natural Infection.

Strong Cellular Immune Response, but Not Humoral, against SARS-CoV-2 in Oncohematological Patients with Autologous Stem Cell Transplantation after Natural Infection. Vigón L, Sánchez-Tornero A, Rodríguez-Mora S, García-Pérez J, Corona de Lapuerta M, Pérez-Lamas L, Casado-Fernández G, Moreno G, Torres M, Mateos E, Murciano-Antón MA, Alcamí J, Pérez-Olmeda M, López-Jiménez J, García-Gutiérrez V, Coiras M (AC). J Clin Med. 2022 Apr 11;11(8):2137. doi: 10.3390/jcm11082137. PMID: 35456230.

PUBMED DOI

Persistent overactive cytotoxic immune response in a Spanish cohort of individuals with Long-COVID: Identification of diagnostic biomarkers

Persistent overactive cytotoxic immune response in a Spanish cohort of individuals with Long-COVID: Identification of diagnostic biomarkers. Galán M, Vigón L, Fuertes D, Murciano-Antón MA, Casado-Fernández G, Domínguez-Mateos S, Mateos E, Ramos-Martín F, Planelles V, Torres M, Rodríguez-Mora S, López-Huertas MR, Coiras M (CA). Front Immunol. 2022 Mar 25;13:848886. doi: 10.3389/fimmu.2022.848886. PMID: 35401523

PUBMED DOI

Content with Investigacion Inmunobiología .

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 .