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
What’s in a name? Species-wide whole-genome sequencing resolves invasive and noninvasive lineages of Salmonella enterica serotype Paratyphi B
7. Connor, T.R., Owen, S.V., Langridge, G., Connell, S., Nair, S., Reuter, S., Dallman, T.J., Corander, J., Tabing, K.C., Le Hello, S., Fookes, M., Doublet, B., Zhou, Z., Feltwell, T., Ellington, M.J., Herrera, S., Gilmour, M., Cloeckaert, A., Achtman, M., Parkhill, J., Wain, J., De Pinna, E., Weill, F.-X., Peters, T., Thomson, N. What’s in a name? Species-wide whole-genome sequencing resolves invasive and noninvasive lineages of Salmonella enterica serotype Paratyphi B (2016) mBio, 7 (4).
PUBMED DOIInvasive salmonella infections among children from Rural Mozambique, 2001-2014
9. Mandomando, I., Bassat, Q., Sigaúque, B., Massora, S., Quintó, L., Ácacio, S., Nhampossa, T., Vubil, D., Garrine, M., Macete, E., Aide, P., Sacoor, C., Herrera-León, S., Ruiz, J., Tennant, S.M., Menéndez, C., Alonso, P.L. Invasive salmonella infections among children from Rural Mozambique, 2001-2014 (2015) Clinical Infectious Diseases, 61, pp. S339-S345.
PUBMED DOIFrecuencia de sustituciones relevantes asociadas a resistencia en la región NS5A a elbasvir en el virus de la hepatitis C en pacientes con genotipo 1a en España
2. Palladino C, Esteban-Cartelle B, Mate-Cano I, Sánchez-Carrillo M, Resino S, Briz V. Frecuencia de sustituciones relevantes asociadas a resistencia en la región NS5A a elbasvir en el virus de la hepatitis C en pacientes con genotipo 1a en España Enferm Infecc Microbiol Clin. 2018; 36 (5): 262-267. (A; FI= 1.707; Q2 Microbiology).
PUBMED DOIDevelopment of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides.
4. Briz V, Sepulveda-Crespo D, Diniz AR; Borrego P, Rodes B; Javier de la Mata F, Gomez R, Taveira N, Muñoz-Fernandez MA. Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides. Nanoscale 2015, 7(35): 14669-14683. (A; FI= 7.76; D1 Materials Science, Multidisciplinary).
PUBMED DOIHepatitis A outbreak disproportionately affecting men who have sex with men (MSM) in the European Union and European Economic Area, June 2016 to May 2017.
6. Hepatitis A outbreak disproportionately affecting men who have sex with men (MSM) in the European Union and European Economic Area, June 2016 to May 2017. Ndumbi P, Freidl GS, Williams CJ, Mårdh O, Varela C, Avellón A, …. Severi E; Members Of The European Hepatitis A Outbreak Investigation Team. Euro Surveill. 2018 Aug;23(33). doi: 10.2807/1560-7917.ES.2018.23.33.1700641.
PUBMED DOIDetection of hepatitis C virus (HCV) core-specific antibody suggests occult HCV infection among blood donors
7. Detection of hepatitis C virus (HCV) core-specific antibody suggests occult HCV infection among blood donors. Quiroga JA, Avellón A, Bartolomé J, Andréu M, Flores E, González MI, González R, Pérez S, Richart LA, Castillo I, Alcover J, Palacios R, Carreño V, Echevarría JM. Transfusion. 2016 Jul;56(7):1883-90. Epub 2016 May 17.
PUBMED DOIHepatitis E virus: Assessment of the epidemiological situation in humans in Europe, 2014/15.
8. Hepatitis E virus: Assessment of the epidemiological situation in humans in Europe, 2014/15. Adlhoch C, Avellon A, Baylis SA, Ciccaglione AR, Couturier E, de Sousa R, Epštein J, Ethelberg S, Faber M, Fehér Á, Ijaz S, Lange H, Manďáková Z, Mellou K, Mozalevskis A, Rimhanen-Finne R, Rizzi V, Said B, Sundqvist L, Thornton L, Tosti ME, van Pelt W, Aspinall E, Domanovic D, Severi E, Takkinen J, Dalton HR. J Clin Virol. 2016 Sep;82:9-16. Epub 2016 Jun 23.
PUBMED DOIFull coding hepatitis E virus genotype 3 genome amplification method
9. Full coding hepatitis E virus genotype 3 genome amplification method. Muñoz-Chimeno M, Forero JE, Echevarría JM, Muñoz-Bellido JL, Vázquez-López L, Morago L, García-Galera MC, Avellón A. J Virol Methods. 2016 Apr;230:18-23. Epub 2016 Jan 16.
PUBMED DOIAntigenicity of Leishmania-Activated C-Kinase Antigen (LACK) in Human Peripheral Blood Mononuclear Cells, and Protective Effect of Prime-Boost Vaccination With pCI-neo-LACK Plus Attenuated LACK-Expressing Vaccinia Viruses in Hamsters
2. Fernández L, Carrillo E, Sánchez-Sampedro L, Sánchez C, Ibarra-Meneses AV, Jimenez MA, Almeida VDA, Esteban M, Moreno J. Antigenicity of Leishmania-Activated C-Kinase Antigen (LACK) in Human Peripheral Blood Mononuclear Cells, and Protective Effect of Prime-Boost Vaccination With pCI-neo-LACK Plus Attenuated LACK-Expressing Vaccinia Viruses in Hamsters. Front Immunol. 2018 Apr 23;9:843.
PUBMED DOIInterleukin-2 as a marker for detecting asymptomatic individuals in areas where Leishmania infantum is endemic.
5. Ibarra-Meneses AV, Carrillo E, Sánchez C, García-Martínez J, López Lacomba D, San Martin JV, Alves F, Alvar J, Moreno J. Interleukin-2 as a marker for detecting asymptomatic individuals in areas where Leishmania infantum is endemic. Clin Microbiol Infect. 2016 Aug;22(8):739.e1-4.
PUBMED DOIProtein malnutrition impairs the immune response and influences the severity of infection in a hamster model of chronic visceral leishmaniasis.
7. Carrillo E, Jimenez MA, Sanchez C, Cunha J, Martins CM, da Paixão Sevá A, Moreno J. Protein malnutrition impairs the immune response and influences the severity of infection in a hamster model of chronic visceral leishmaniasis. PLoS One. 2014 Feb 25;9(2):e89412.
PUBMED DOIMolecular typing of Leishmania infantum isolates from a leishmaniasis outbreak in Madrid, Spain, 2009 to 2012
9. Chicharro C, Llanes-Acevedo IP, García E, Nieto J, Moreno J, Cruz I. Molecular typing of Leishmania infantum isolates from a leishmaniasis outbreak in Madrid, Spain, 2009 to 2012. Euro Surveill. 2013 Jul 25;18(30):20545.
PUBMED DOIHigh levels of anti-Phlebotomus perniciosus saliva antibodies in different reservoirs from the re-emerging leishmaniasis focus in Madrid, Spain.
2. Martín-Martín I, Molina R, Rohoušová I, Drahota J., Volf P, Jiménez M. High levels of anti-Phlebotomus perniciosus saliva antibodies in different reservoirs from the re-emerging leishmaniasis focus in Madrid, Spain. Vet Parasitol 2014, 202: 207–216.
PUBMED DOICould wild rabbits (Oryctolagus cuniculus) be reservoirs for Leishmania infantum in the focus of Madrid, Spain?
3. Jiménez M, González E, Martín-Martín I, Hernández S, Molina R. Could wild rabbits (Oryctolagus cuniculus) be reservoirs for Leishmania infantum in the focus of Madrid, Spain?. Vet Parasitol 2014, 202: 296–300.
PUBMED DOIReview of ten-years presence of Aedes albopictus in Spain 2004–2014: known distribution and public health concerns.
5. Collantes F, Delacour S, Alarcón-Elbal PM, Ruiz-Arrondo I, Delgado JA, Torrell-Sorio A, Bengoa M, Eritja R, Miranda MA, Molina R, Lucientes J. Review of ten-years presence of Aedes albopictus in Spain 2004–2014: known distribution and public health concerns. Parasit Vectors. 2015 Dec 23;8:655.
PUBMED DOIPhleboviruses detection in Phlebotomus perniciosus from a human leishmaniasis focus in South-West Madrid region, Spain.
6. Remoli ME, Jiménez M, Fortuna C, Benedetti E, Marchi A, Genovese D, Gramiccia M, Molina R, Ciufolini MG. Phleboviruses detection in Phlebotomus perniciosus from a human leishmaniasis focus in South-West Madrid region, Spain. Parasit Vectors 2016, 9:205.
PUBMED DOIInfectivity of Post-Kala-azar Dermal Leishmaniasis patients to sand flies: revisiting a proof of concept in the context of the Kala-azar Elimination Program in the Indian subcontinent.
7. Molina R, Ghosh D, Carrillo E, Monnerat S, Bern C, Mondal D, Alvar J. Infectivity of Post-Kala-azar Dermal Leishmaniasis patients to sand flies: revisiting a proof of concept in the context of the Kala-azar Elimination Program in the Indian subcontinent. Clin Infect Dis 2017, 65:
PUBMED DOIPrevalence and molecular characterization of Strongyloides stercoralis, Giardia duodenalis, Cryptosporidium spp., and Blastocystis spp. isolates in schoolchildren in Cubal, Central Angola
2. Dacal E, Saugar JM, de Lucio A, Hernández de Mingo M, Robinson E, Aznar Ruiz de Alegría ML, Espasa M, Ninda A, Gandasegui J, Sulleiro E, Moreno M, Salvador F, Molina I, Rodríguez E, Carmena D. 2018. Prevalence and molecular characterization of Strongyloides stercoralis, Giardia duodenalis, Cryptosporidium spp., and Blastocystis spp. isolates in schoolchildren in Cubal, Central Angola. Parasites and Vectors, 11: 67.
PUBMED DOIMolecular diversity and frequency of the diarrheagenic enteric protozoan Giardia duodenalis and Cryptosporidium spp. in a hospital setting in Northern Spain.
3. Azcona-Gutiérrez JM, de Lucio A, Hernández-de-Mingo M, García-García C, Soria-Blanco LM, Morales L, Aguilera M, Fuentes I, Carmena D. 2017. Molecular diversity and frequency of the diarrheagenic enteric protozoan Giardia duodenalis and Cryptosporidium spp. in a hospital setting in Northern Spain. PLoS One, 12: e0178575.
PUBMED DOIDetection of zoonotic protozoa Toxoplasma gondii and Sarcocystis suihominis in wild boars from Spain. Zoonoses Public Health
4. Calero-Bernal, R., Pérez-Martín, J.E., Reina, D., Serrano, F.J., Frontera, E., Fuentes, I, Dubey, J.P., 2016. Detection of zoonotic protozoa Toxoplasma gondii and Sarcocystis suihominis in wild boars from Spain. Zoonoses Public Health. 63:346-50
PUBMED DOIContent with Investigacion .
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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