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Medical Entomology

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

Content with Investigacion Virología Molecular .

- 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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Epidemiological trend of hepatitis C-related liver events in Spain (2000-2015): A nationwide population-based study.

7. Rivero-Juárez A, Dashti A, López-López P, Salimo Muadica A, Risalde MA, Köster PC, Machuca I, Bailo B, Hernández de Mingo M, Dacal E, García-Bocanegra I, Saugar JM, Calero-Bernal R, González-Barrio D, Rivero A, Briz V, Carmena D. Protist enteroparasites in wild boar (Sus scrofa ferus) and black Iberian pig (Sus scrofa domesticus) in southern Spain: a protective effect on hepatitis E acquisition? Parasites & Vectors 2020, 13: 281

PUBMED DOI

Nanotechnology: A reality for diagnosis of HCV infectious disease.

Arca-Lafuente S, Martínez-Román P, Mate-Cano I, Madrid R, Briz V. Nanotechnology: A reality for diagnosis of HCV infectious disease. Journal of Infection 2020, 80 (1); 8-15.

PUBMED DOI

Multidisciplinary Group of viral coinfection HIV/Hepatitis (COVIHEP). HCV-coinfection is related to an increased HIV-1 reservoir size in cART-treated HIV patients: a cross-sectional study.

López-Huertas MR, Palladino C, Garrido-Arquero M, Esteban-Cartelle B, Sánchez-Carrillo M, Martínez-Román P, Martín-Carbonero L, Ryan P, Domínguez-Domínguez L, Santos ID, Moral SDLF, Benito JM, Rallón N, Alcamí J, Resino S, Fernández-Rodríguez A, Coiras M, Briz V*, on behalf of the Multidisciplinary Group of viral coinfection HIV/Hepatitis (COVIHEP). HCV-coinfection is related to an increased HIV-1 reservoir size in cART-treated HIV patients: a cross-sectional study. Sci Rep 2019: 9 (1); 5606.

PUBMED DOI

Persistent Low-Level Viremia in treatment HIV infection: An unresolved status.

3. Crespo-Bermejo C, Ramírez de Arellano E, Lara-Aguilar V, Martínez-Román P, Arca Lafuente S, Gómez-Lus ML, Martín-Carbonero L, Briz V. Persistent Low-Level Viremia in treatment HIV infection: An unresolved status. Virulencia 2021, 12: 2919-2931.

PUBMED DOI

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. Full coding hepatitis E virus genotype 3 genome amplification method. J Virol Methods. 2016 Apr;230:18-23.

PUBMED DOI

Comparative sensitivity of commercial tests for hepatitis E genotype 3 virus antibody detection.

• Avellón A, Morago L, García-Galera del Carmen M, Muñoz M, Jose-Manuel Echevarría JM. Comparative sensitivity of commercial tests for hepatitis E genotype 3 virus antibody detection. J Med Virol. 2015 Nov;87(11):1934-9.

PUBMED DOI

Epidemiology and predictive factors for early and late mortality in Candida bloodstream infections: a population-based surveillance in Spain

11: Puig-Asensio M, Padilla B, Garnacho-Montero J, Zaragoza O, Aguado JM, Zaragoza R, Montejo M, Muñoz P, Ruiz-Camps I, Cuenca-Estrella M, Almirante B; CANDIPOP Project; GEIH-GEMICOMED (SEIMC); REIPI. Epidemiology and predictive factors for early and late mortality in Candida bloodstream infections: a population-based surveillance in Spain. Clin Microbiol Infect. 2014 Apr;20(4):O245-54.

PUBMED DOI

B Pérez de Val, B Romero, MT Tórtola, L Herrera-León, P Pozo, I Mercader, JL Sáez, M Domingo, E Vidal. Poly-resistant Mycobacterium bovis infection in a human and sympatric sheep, Spain, 2017-2018

B Pérez de Val, B Romero, MT Tórtola, L Herrera-León, P Pozo, I Mercader, JL Sáez, M Domingo, E Vidal. Poly-resistant Mycobacterium bovis infection in a human and sympatric sheep, Spain, 2017-2018. Emerg Infect Dis. 2021 Apr;27(4):1241-1243. doi: 10.3201/eid2704.204467. PMID: 33755008.

DOI

L Bernal-Martínez; L Herrera-Leon; C Valero; P de la Cruz; L Ghimpu; AC Mesa-Arango; G Santoni; L Goterris; R Millán; MJ Buitrago. Differential Diagnosis of Fungal Pneumonias vs.Tuberculosis in AIDS Patients by Using Two New Molecular Methods.

L Bernal-Martínez; L Herrera-Leon; C Valero; P de la Cruz; L Ghimpu; AC Mesa-Arango; G Santoni; L Goterris; R Millán; MJ Buitrago. Differential Diagnosis of Fungal Pneumonias vs.Tuberculosis in AIDS Patients by Using Two New Molecular Methods. J. Fungi 2021, 7, 336. doi.org: 10.3390/jof7050336. PMID: 33925404.

DOI

E Tagliani, RAnthony, TA Kohl, A de Neeling, V Nikolayevskyy, C Ködmön, FP Maurer, S Niemann, D van Soolingen, MJ van der Werf, D Cirillo, ECDC molecular surveillance project participants. Use of a whole genome sequencing-based approach for Mycobacterium tuberculosis surveillance in Europe in 2017-2019: an ECDC pilot study

E Tagliani, RAnthony, TA Kohl, A de Neeling, V Nikolayevskyy, C Ködmön, FP Maurer, S Niemann, D van Soolingen, MJ van der Werf, D Cirillo, ECDC molecular surveillance project participants. Use of a whole genome sequencing-based approach for Mycobacterium tuberculosis surveillance in Europe in 2017-2019: an ECDC pilot study. Eur Respir J. 2021 Jan 5;57(1):2002272. doi: 10.1183/13993003.02272-2020. Print 2021 Jan. PMID: 32732329.

DOI

MJ Iglesias, D Ibarz, A Cebollada, J Comín, MS Jiménez, MC Vázquez, S Samper, Spanish Working Group on MDRTB. The value of the continuous genotyping of multidrug resistant tuberculosis over 20 years in Spain.

MJ Iglesias, D Ibarz, A Cebollada, J Comín, MS Jiménez, MC Vázquez, S Samper, Spanish Working Group on MDRTB. The value of the continuous genotyping of multidrug resistant tuberculosis over 20 years in Spain. Sci Rep. 2020 Nov 24;10(1):20433. doi: 10.1038/s41598-020-77249-x. PMID: 33235225.

DOI

S Campos-Gutierrez, MJ Ramos-Real, R Abreu, MS Jimenez, M Lecuona. Pseudo-ourbreak of Mycobacterium fortuitum, in a hospital bronchoscopy unit.

S Campos-Gutierrez, MJ Ramos-Real, R Abreu, MS Jimenez, M Lecuona. Pseudo-ourbreak of Mycobacterium fortuitum, in a hospital bronchoscopy unit. Am J Infect Control. 2020 Jul;48(7):765-769. doi: 10.1016/j.ajic.2019.11.019. Epub 2019 Dec 24. PMID: 31882175.

DOI

Gascha , Y Meijeb, M Espasac, B Fonta, MS Jiménez, N Fernández-Hidalgo. Disseminated Infection Due to Mycobacterium chimaera After Aortic Valve Replacement.

Gascha , Y Meijeb, M Espasac, B Fonta, MS Jiménez, N Fernández-Hidalgo. Disseminated Infection Due to Mycobacterium chimaera After Aortic Valve Replacement. Revista Española de cardiología. 2019. Vol 72 (6):502-503. DOI: 10.1016/j.rec.2018.06.026. PMID: 30029979

DOI

PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study

2. Salgüero S, Brochado-Kith O, Virseda Verdices A, Berenguer J, González-García J, Martínez I, Díez C, Hontañón V, Pérez-Latorre L, Fernández-Rodríguez A (‡), Jiménez-Sousa MA (‡,*), and Resino S (‡, *). PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study. Biomed Pharmacother 2023, 159:114220. (A; FI= 7.42; D1, Pharmacology & Pharmacy; JCR 2021). PMID: 36628818. DOI: 10.1016/j.biopha.2023.114220.

PUBMED

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

4. Martin-Vicente M, Almansa R, Martínez I, Tedim AP, Bustamante E, Tamayo L, Aldecoa C, Gómez JM, Renedo G, Berezo JA, Cedeño JA, Mamolar N, García Olivares P, Herrán-Monge R, Cicuendez R, Enríquez P, Ortega A, Jorge N, Doncel C, 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, Domínguez-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, 291(2):232–240. (A; FI= 13.07; D1, Medicine, General & Internal; JCR 2021). PMID: 34611927. DOI: 10.1111/joim.13386.

PUBMED

Prevalence and factors associated with SARS-CoV-2 seropositivity in the Spanish HIV Research Network Cohort

5. Berenguer J (*), Díez C, Martín-Vicente M, Mican R, Pérez-Elías MJ, García-Fraile LJ, Vidal F, Suárez-García I, Podzamcer D, Del Romero J, Pulido F, Iribarren JA, Gutiérrez F, Poveda E, Galera C, Izquierdo R, Asensi V, Portilla J, López JC, Arribas JR, Moreno S, González-García J, Resino S (‡), Jarrín I (‡). Prevalence and factors associated with SARS-CoV-2 seropositivity in the Spanish HIV Research Network Cohort. Clin Microbiol Infect. 2021, 27(11):1678-1684. (A; FI= 13.31; D1, Microbiology; JCR 2021). PMID: 34186209 DOI: 10.1016/j.cmi.2021.06.023.

PUBMED

Environmental factors linked to hospital admissions in young children due to acute viral lower respiratory infections: A bidirectional case-crossover study

6. Álvaro-Meca A, Goez MC, Resino R, Matías V, Sepúlveda-Crespo D; Martínez I, Resino S (*). Environmental factors linked to hospital admissions in young children due to acute viral lower respiratory infections: a bidirectional case-crossover study. Environ Res. 2022. 212(Pt B), 113319. (A; FI= 8.43; D1, Public, Environmental & Occupational Health; JCR 2021). PMID: 35447151. DOI: 10.1016/j.envres.2022.113319.

PUBMED

Detection of active hepatitis C in a single visit and linkage to care among marginalized people using a mobile unit in Madrid, Spain

7. Ryan P, Valencia J, Cuevas G, Torres-Macho J, Troya J, Pueyo A, Muñoz-Gómez MJ, Muñoz-Rivas N, Vázquez-Morón S, Martínez, I, Lazarus JV, Resino S (*). Detection of active hepatitis C in a single visit and link-to-care among excluded people using a mobile unit in Madrid, Spain. Int J Drug Policy. 2021, 96:103424. (A; FI= 5.93; Q1, Substance Abuse; JCR 2021). PMID: 34429222 DOI: 10.1016/j.drugpo.2021.103424.

PUBMED

María José Ruiz-Lopéz, Milagros Muñoz-Chimeno, Jordi Figuerola, Ana M. Gavilán, Sarai Varona, Isabel Cuesta, Josué Martínez-de la Puente, Angel Zaballos, Francisca Molero, Ramón C. Soriguer, Mª Paz Sánchez-Seco, Santiago Ruiz, Ana Vázquez. Genomic analysis of West Nile virus lineage 1 isolated from mosquitoes

María José Ruiz-Lopéz, Milagros Muñoz-Chimeno, Jordi Figuerola, Ana M. Gavilán, Sarai Varona, Isabel Cuesta, Josué Martínez-de la Puente, Angel Zaballos, Francisca Molero, Ramón C. Soriguer, Mª Paz Sánchez-Seco, Santiago Ruiz, Ana Vázquez. Genomic analysis of West Nile virus lineage 1 isolated from mosquitoes from 2020-2021 outbreak occurred in Andalusia, Spain. Viruses 2023, 15, 266. https://doi.org/10.3390/v15020266

DOI

Jordi Figuerola, Miguel Ángel Jiménez-Clavero, María José Ruíz-López, Francisco Llorente, Santiago Ruiz, Andreas Hoefer, Pilar Aguilera-Sepúlveda, Jéssica Jiménez Peñuela1, Olaya García-Ruiz, Laura Herrero, Ramón C. Soriguer, Raúl Fernández Delgado, Mari Paz Sánchez-Seco, Josué Martínez-de la Puente, Ana Vázquez. A One Health view of the West Nile virus outbreak in Andalusía (Spain) in 2020

Jordi Figuerola, Miguel Ángel Jiménez-Clavero, María José Ruíz-López, Francisco Llorente, Santiago Ruiz, Andreas Hoefer, Pilar Aguilera-Sepúlveda, Jéssica Jiménez Peñuela1, Olaya García-Ruiz, Laura Herrero, Ramón C. Soriguer, Raúl Fernández Delgado, Mari Paz Sánchez-Seco, Josué Martínez-de la Puente, Ana Vázquez. A One Health view of the West Nile virus outbreak in Andalusía (Spain) in 2020. Emerg Microbes Infect. 2022 Dec;11(1):2570-2578. doi: 10.1080/22221751.2022.2134055.

DOI

Content with Investigacion Investigación sobre Anomalías Congénitas .

Additional Information

The Medical Entomology Laboratory has accumulated extensive experience in this field, especially in entomological field studies, biology of arthropods of medical interest, vector competence and vector control. Also, in the molecular detection of Leishmania infantum promastigotes in naturally parasitized phlebotomine sand flies, in the molecular identification of blood ingested by hematophagous arthropods and in the study of the immunomodulatory properties of proteins present in the saliva of phlebotomine sand flies and mosquitoes. Our laboratory is currently co-leading the studies of vectors and wild reservoirs of leishmaniasis in the leishmaniasis focus of Fuenlabrada, Madrid. In this sense, we have studied the role of asymptomatic individuals as reservoirs in the outbreak by xenodiagnosis. On the other hand, we have participated since 2007 in the Entomological Surveillance Program in Airports and Ports against Potential Vectors of Exotic Infectious Diseases, a program that is allowing to develop the expansion map in Spain of Aedes albopictus. In 2016-2017, we carried out surveillance of Ae. albopictus in the Community of Castilla-La Mancha. On the other hand, we conducted studies on the role of patients with post-kala-azar dermal leishmaniasis (PKDL) in the transmission of the parasite in Bangladesh and Sudan. In addition, we participate in research studying ticks transmitting Crimean-Congo hemorrhagic fever in Spain.

Currently, it maintains confidentiality agreements with several companies participating in the evaluation of molecules with activity against pathogens in vectors (GSK), in the development of vector traps using artificial intelligence algorithms (Irideon, Spain), and in the evaluation of repellents against phlebotomine sand flies (IRSEA, France).

The laboratory actively participates in outreach activities such as the Science Week or the European Researchers' Night, among others, making medical entomology science available to the general population.

The Medical Entomology Laboratory has accumulated extensive experience in this field, especially in entomological field studies, biology of arthropods of medical interest, vector competence and vector control. Also, in the molecular detection of Leishmania infantum promastigotes in naturally parasitized phlebotomine sand flies, in the molecular identification of blood ingested by hematophagous arthropods and in the study of the immunomodulatory properties of proteins present in the saliva of phlebotomine sand flies and mosquitoes. Our laboratory is currently co-leading the studies of vectors and wild reservoirs of leishmaniasis in the leishmaniasis focus of Fuenlabrada, Madrid. In this sense, we have studied the role of asymptomatic individuals as reservoirs in the outbreak by xenodiagnosis. On the other hand, we have participated since 2007 in the Entomological Surveillance Program in Airports and Ports against Potential Vectors of Exotic Infectious Diseases, a program that is allowing to develop the expansion map in Spain of Aedes albopictus. In 2016-2017, we carried out surveillance of Ae. albopictus in the Community of Castilla-La Mancha. On the other hand, we conducted studies on the role of patients with post-kala-azar dermal leishmaniasis (PKDL) in the transmission of the parasite in Bangladesh and Sudan. In addition, we participate in research studying ticks transmitting Crimean-Congo hemorrhagic fever in Spain.

Currently, it maintains confidentiality agreements with several companies participating in the evaluation of molecules with activity against pathogens in vectors (GSK), in the development of vector traps using artificial intelligence algorithms (Irideon, Spain), and in the evaluation of repellents against phlebotomine sand flies (IRSEA, France).

The laboratory actively participates in outreach activities such as the Science Week or the European Researchers' Night, among others, making medical entomology science available to the general population.

Content with Investigacion Investigación sobre Anomalías Congénitas .