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:
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Diagnosis and reference of HIV infection (types 1 and 2) through detection of specific antibodies and detection of proviral DNA by PCR.
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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.
Publications
Off-label use of maraviroc in HIV-1-infected paediatric patients in clinical practice.
Palladino C, Navarro Gomez ML, Soler-Palacin P, Gonzalez-Tome MI, Jiménez de Ory S, Espiau M, Pérez-Hoyos S, León-Leal JA, Méndez M, Moreno-Pérez D, Fortuny C, uer A, Pocheville I, Moreno S, Briz V, on behalf of the CoRISpe Working Group. Off-label use of maraviroc in HIV-1-infected paediatric patients in clinical practice. AIDS 2015; 29-16, pp.2155-2159. (A; FI= 4,407; Q1 Infectious Disease).
PUBMED DOIComparative sensitivity of commercial tests for hepatitis E genotype 3 virus antibody detection.
Comparative sensitivity of commercial tests for hepatitis E genotype 3 virus antibody detection. Avellon A, Morago L, Garcia-Galera del Carmen M, Munoz M, Echevarría JM. J Med Virol. 2015 Nov;87(11):1934-9. Epub 2015 May 29.
PUBMED DOIRelative telomere length impact on mortality of COVID-19: sex differences.
Virseda-Berdices A, Concostrina-Martinez L, Martínez-González O, Blancas R, Resino S, Ryan P, De Juan C, Moreira-Escriche P, Martin-Vicente M, Brochado-Kith O, Blanca-López N, Jiménez-Sousa MA (‡,*), Fernández-Rodríguez A (‡). Relative telomere length impact on mortality of COVID-19: sex differences. J Med Virol 2023; 98 (1): e28368 (A; FI= 20.96; D1, Virology; JCR 2021).
PUBMEDActivity of host antimicrobials against multidrug resistant Acinetobacter baumannii acquiring colistin resistance through loss of lipopolysaccharide
García-Quintanilla, M., Pulido, M. R., Moreno-Martínez, P., Martín-Peña, R., López-Rojas, R., Pachón, J. and McConnell, M.J.* Activity of host antimicrobials against multidrug resistant Acinetobacter baumannii acquiring colistin resistance through loss of lipopolysaccharide. Antimicrobial Agents and Chemotherapy 2014. May;58(5):2972-5.
PUBMED DOICharacterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors
Characterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors. González N, McKee K, Lynch RM, Georgiev IS, Jimenez L, Grau E, Yuste E, Kwong PD, Mascola JR, Alcamí J. PLoS One. 2018;13:e0193773.
PUBMED DOIDiverse large HIV-1 non-subtype B clusters are spreading among men who have sex with men in Spain
Delgado E, Benito S, Montero V, Cuevas MT, Fernández-García A, Sánchez-Martínez M, García-Bodas E, Díez-Fuertes F, Gil H, Cañada J, Carrera C, Martínez-López J, Sintes M, Pérez-Álvarez L, Thomson MM; Spanish Group for the Study of New HIV Diagnoses. Diverse large HIV-1 non-subtype B clusters are spreading among men who have sex with men in Spain. Front Microbiol. 2019; 3;10:655.
PUBMED DOIImprovement of HIV-1 coreceptor tropism prediction by employing selected nucleotide positions of the env gene in a Bayesian network classifier.
Díez-Fuertes F, Delgado E, Vega Y, Fernández-García A, Cuevas MT, Pinilla M, García V, Pérez-Álvarez L, Thomson MM. Improvement of HIV-1 coreceptor tropism prediction by employing selected nucleotide positions of the env gene in a Bayesian network classifier. J Antimicrob Chemother. 2013; 68:1471-1485.
PUBMED DOIPredominance of CXCR4 tropism in HIV-1 CRF14_BG strains from newly diagnosed infections.
Pérez-Álvarez L, Delgado E, Vega Y, Montero V, Cuevas T, Fernández-García A, García-Riart B, Pérez-Castro S, Rodríguez-Real R, López-Álvarez MJ, Fernández-Rodríguez R, Lezaun MJ, Ordóñez P, Ramos C, Bereciartua E, Calleja S, Sánchez-García AM, Thomson MM. Predominance of CXCR4 tropism in HIV-1 CRF14_BG strains from newly diagnosed infections. J Antimicrob Chemother. 2014; 69:246-253.
PUBMED DOIMolecular epidemiology, phylogeny, and phylodynamics of CRF63_02A1, a recently originated HIV-1 circulating recombinant form spreading in Siberia.
Shcherbakova NS, Shalamova LA, Delgado E, Fernández-García A, Vega Y, Karpenko LI, Ilyichev AA, Sokolov YV, Shcherbakov DN, Pérez-Álvarez L, Thomson MM. Molecular epidemiology, phylogeny, and phylodynamics of CRF63_02A1, a recently originated HIV-1 circulating recombinant form spreading in Siberia. AIDS Res Hum Retroviruses. 2014; 30:912-919.
PUBMED DOIEpidemiological surveillance of HIV-1 transmitted drug resistance in Spain in 2004-2012: relevance of transmission clusters in the propagation of resistance mutations.
Vega Y, Delgado E, Fernández-García A, Cuevas MT, Thomson MM, Montero V, Sánchez M, Sánchez AM, Pérez-Álvarez L; Spanish Group for the Study of New HIV-1 Diagnoses in Galicia and Basque Country. Epidemiological surveillance of HIV-1 transmitted drug resistance in Spain in 2004-2012: relevance of transmission clusters in the propagation of resistance mutations. PLoS One. 2015; 10:e0125699.
PUBMED DOIPhylogeny and phylogeography of a recent HIV-1 subtype F outbreak among men who have sex with men in Spain deriving from a cluster with a wide geographic circulation in Western Europe.
Delgado E, Cuevas MT, Domínguez F, Vega Y, Cabello M, Fernández-García A, Pérez-Losada M, Castro MÁ, Montero V, Sánchez M, Mariño A, Álvarez H, Ordóñez P, Ocampo A, Miralles C, Pérez-Castro S, López-Álvarez MJ, Rodríguez R, Trigo M, Diz-Arén J, Hinojosa C, Bachiller P, Hernáez-Crespo S, Cisterna R, Garduño E, Pérez-Álvarez L, Thomson MM. Phylogeny and phylogeography of a recent HIV-1 subtype F outbreak among men who have sex with men in Spain deriving from a cluster with a wide geographic circulation in Western Europe. PLoS One. 2015; 10:e0143325.
PUBMED DOIIdentification of an HIV-1 BG intersubtype recombinant form (CRF73_BG), partially related to CRF14_BG, which Is circulating in Portugal and Spain.
Fernández-García A, Delgado E, Cuevas MT, Vega Y, Montero V, Sánchez M, Carrera C, López-Álvarez MJ, Miralles C, Pérez-Castro S, Cilla G, Hinojosa C, Pérez-Álvarez L, Thomson MM. Identification of an HIV-1 BG intersubtype recombinant form (CRF73_BG), partially related to CRF14_BG, which Is circulating in Portugal and Spain. PLoS One. 2016; 11:e0148549.
PUBMED DOISequence analysis of in vivo-expressed HIV-1 spliced RNAs reveals the usage of new and unusual splice sites by viruses of different subtypes
Vega Y, Delgado E, de la Barrera J, Carrera C, Zaballos Á, Cuesta I, Mariño A, Ocampo A, Miralles C, Pérez-Castro S, Álvarez H, López-Miragaya I, García-Bodas E, Díez-Fuertes F, Thomson MM. Sequence analysis of in vivo-expressed HIV-1 spliced RNAs reveals the usage of new and unusual splice sites by viruses of different subtypes. PLoS One. 2016; 11:e0158525.
PUBMED DOIHIV-1 genetic diversity in recently diagnosed infections in Moscow: predominance of AFSU, frequent branching in clusters, and circulation of the Iberian subtype G variant.
Karamov E, Epremyan K, Siniavin A, Zhernov Y, Cuevas MT, Delgado E, Sánchez-Martínez M, Carrera C, Kornilaeva G, Turgiev A, Bacqué J, Pérez-Álvarez L, Thomson MM. HIV-1 genetic diversity in recently diagnosed infections in Moscow: predominance of AFSU, frequent branching in clusters, and circulation of the Iberian subtype G variant. AIDS Res Hum Retroviruses. 2018; 34:629-634.
PUBMED DOIBayesian phylogeographic analyses clarify the origin of the HIV-1 subtype A variant circulating in former Soviet Union's countries.
Díez-Fuertes F, Cabello M, Thomson MM. Bayesian phylogeographic analyses clarify the origin of the HIV-1 subtype A variant circulating in former Soviet Union's countries. Infect Genet Evol. 2015; 33:197-205.
PUBMED DOIAlcazar-Fuoli L, Clavaud C, Lamarre C, Aimanianda V, Seidl-Seiboth V, Mellado E, Latgé JP. Functional analysis of the fungal/plant class chitinase family in Aspergillus fumigatus.
Alcazar-Fuoli L, Clavaud C, Lamarre C, Aimanianda V, Seidl-Seiboth V, Mellado E, Latgé JP. Functional analysis of the fungal/plant class chitinase family in Aspergillus fumigatus. Fungal Genet Biol. 2011 Apr;48(4):418-29. doi: 10.1016/j.fgb.2010.12.007. Epub 2010 Dec 22. PMID: 21184840.
PUBMED DOIImpact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study.
Jiménez-Sousa MA (AC); Gómez-Moreno AZ; Pineda-Tenor D; et al. (1/9) Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study. Biomolecules 2019; 9(4).
DBP rs16846876 and rs12512631 polymorphisms are associated with progression to AIDS naïve HIV-infected patients: a retrospective study.
Jiménez-Sousa MA (AC); Jiménez JL; Fernández-Rodríguez A; et al. (1/10). DBP rs16846876 and rs12512631 polymorphisms are associated with progression to AIDS naïve HIV-infected patients: a retrospective study. Journal of Biomedical Science. 2019; 23;26(1):83. doi: 10.1186/s12929-019-0577-y.
TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients.Journal of Clinical Medicine.
Resino S; Fernández-Rodríguez A; Pineda-Tenor D; et al; Jiménez-Sousa MA. (11/11). 2021. TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients.Journal of Clinical Medicine. 10-3, pp.483. ISSN 2077-0383. https://doi.org/10.3390/jcm10030483.
Plasma metabolomic fingerprint of advanced cirrhosis stages among HIV/HCV-coinfected and HCV-monoinfected patients
Salguero, Sergio; Rojo, David; Berenguer, Juan; et al; Jimenez-Sousa, Maria A. (AC) (15/15). 2020. Plasma metabolomic fingerprint of advanced cirrhosis stages among HIV/HCV-coinfected and HCV-monoinfected patients LIVER INTERNATIONAL. 40-9, pp.2215-2227. ISSN 1478-3223. https://doi.org/10.1111/liv.14580 3
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Concepción Casado Herrero
Tenure Scientist of Public Research Organizations (OPIs)
ORCID code: 0000-0003-3412-2877
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María Pernas Escario
Senior Specialized Technician of Public Research Organizations (OPIs)
ORCID code: 0000-0003-2966-0160
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Virginia Sandonís Martín
Senior Specialized Technician of Public Research Organizations (OPIs)
ORCID code: 0000-0001-5762-7531
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Rosa Fuentes Fernández
Laboratory Technician
List of staff