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Investigación

Leishmaniasis and Chagas Disease

Líneas de investigación

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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.

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Publicaciones destacadas

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Kinetics of anti-Phlebotomus perniciosus saliva antibodies in experimentally bitten mice and rabbits.

Martín-Martín I, Molina R, Jiménez M. Kinetics of anti-Phlebotomus perniciosus saliva antibodies in experimentally bitten mice and rabbits. PLoS ONE, November 16, 2015; 10(11):

PUBMED DOI

Identifying salivary antigens of Phlebotomus argentipes by a 2DE approach.

Martín-Martín I, Molina R, Jiménez M. Identifying salivary antigens of Phlebotomus argentipes by a 2DE approach. Acta Trop 2013, 126: 229–239.

PUBMED DOI

Factors associated with Leishmania asymptomatic infection: results from a cross-sectional survey in highland northern Ethiopia

Custodio E, Gadisa E, Sordo L, Cruz I, Moreno J, Nieto J, Chicharro C, Aseffa A, Abraham Z, Hailu T, Cañavate C. Factors associated with Leishmania asymptomatic infection: results from a cross-sectional survey in highland northern Ethiopia. PLoS Negl Trop Dis. 2012;6(9):e1813.

PUBMED DOI

Cytokine Release Assays as Tests for Exposure to Leishmania, and for Confirming Cure from Leishmaniasis, in Solid Organ Transplant Recipients.

Carrillo E, Carrasco-Antón N, López-Medrano F, Salto E, Fernández L, San Martín JV, Alvar J, Aguado JM, Moreno J. Cytokine Release Assays as Tests for Exposure to Leishmania, and for Confirming Cure from Leishmaniasis, in Solid Organ Transplant Recipients. PLoS Negl Trop Dis. 2015 Oct 23;9(10):e0004179.

PUBMED DOI

Chemotactic Protein 1 in Plasma from Soluble Leishmania Antigen-Stimulated Whole Blood as a Potential Biomarker of the Cellular Immune Response to Leishmania infantum

Ibarra-Meneses AV, Sanchez C, Alvar J, Moreno J, Carrillo E. Monocyte Chemotactic Protein 1 in Plasma from Soluble Leishmania Antigen-Stimulated Whole Blood as a Potential Biomarker of the Cellular Immune Response to Leishmania infantum. Front Immunol. 2017 Sep 29;8:1208.

PUBMED DOI

Cytokines and chemokines measured in dried SLA-stimulated whole blood spots for asymptomatic Leishmania infantum and Leishmania donovani infection.

Ibarra-Meneses AV, Mondal D, Alvar J, Moreno J, Carrillo E. Cytokines and chemokines measured in dried SLA-stimulated whole blood spots for asymptomatic Leishmania infantum and Leishmania donovani infection. Sci Rep. 2017 Dec 8;7(1):17266.

PUBMED DOI

Cellular Markers of Active Disease and Cure in Different Forms of Leishmania infantum-Induced Disease.

Botana L, Matía B, San Martin JV, Romero-Maté A, Castro A, Molina L, Fernandez L, Ibarra-Meneses A, Aguado M, Sánchez C, Horrillo L, Chicharro C, Nieto J, Ortega S, Ruiz-Giardin JM, Carrillo E, Moreno J. Cellular Markers of Active Disease and Cure in Different Forms of Leishmania infantum-Induced Disease. Front Cell Infect Microbiol. 2018 Nov 13;8:381.

PUBMED DOI

Carroll MW et al. Temporal and spatial analysis of the 2014-2015 Ebola virus outbreak in West Africa. Nature.

Carroll MW et al. Temporal and spatial analysis of the 2014-2015 Ebola virus outbreak in West Africa. Nature. 2015 Aug 6;524(7563):97-101. doi: 10.1038/nature14594. Epub 2015 Jun 17. PMID: 26083749. ​

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List of staff

Información adicional

The Leishmaniasis and Chagas Disease Unit supports the National Health System through a multidisciplinary approach that includes the development and validation of diagnostic tests, the molecular characterization of parasites, molecular epidemiology, field studies, as well as experimental research into new therapeutic and prophylactic approaches for their control.
The laboratory has extensive experience in the characterization of the cellular and humoral immune response of leishmaniasis and post-treatment monitoring, as well as in asymptomatic individuals and in experimental animal models. The laboratory also contributes to immunological studies of the pathogenesis of leishmaniasis under immunosuppressive conditions (HIV/Leishmania co-infection, malnutrition, immunosuppressive treatment...). The laboratory has been a WHO Collaborating Center for Leishmaniasis since 1997, providing technical support to the various research and training activities of the WHO and participating in the evaluation of outbreaks of human leishmaniasis in endemic countries.
The laboratory also participates in the evaluation of prognostic markers for the evolution of T. cruzi infection and vertical (transplacental) transmission, an important public health problem in our country. It also carries out studies on the pharmacokinetics of drugs against Chagas disease.

Content with Investigacion Virología Molecular .