Viral Biology
Research Lines
Content with Investigacion .
The Laboratory of Medical Entomology (LME) develops an intense reference and research activity, focused on the field of disease vectors of interest in Public Health. The LME has an insectary where biological cycles of insect vectors are currently maintained, allowing the performance, among others, of vector competence and xenodiagnostic studies. The LME supports the national health system by offering techniques available in the portfolio of services for the taxonomic identification of arthropods of health interest. In addition, it performs entomological surveillance of outbreaks, supporting Surveillance Plans. In particular, the LME plays a leading role in the Entomological Surveillance Plan for Leishmaniasis in the Community of Madrid. On the other hand, the LME offers scientific advice to the CCAES (Centro de Coordinación de Alertas y Emergencias Sanitarias, Ministerio de Sanidad, Consumo y Bienestar Social), and participates in the elaboration of reports and rapid risk assessments.
The main research lines of the Laboratory of Medical Entomology are:
1. Maintenance of insect vector colonies: phlebotomine sand flies (Phlebotomus perniciosus, Phlebotomus papatasi and Phlebotomus argentipes, vectors of Leishmania infantum, Leishmania major and Leishmania donovani, respectively), Culex and Aedes mosquitoes (vectors of various arboviruses) and Rhodnius prolixus (vector of Trypanosoma cruzi).
2. Biology of disease vectors of public health interest: biology, vector competence, experimental infections. The CNM has a BSL3 safety laboratory to carry out vector competence studies with culicidae and phlebotomine sand flies.
3. Entomological sampling, infectivity of potential reservoirs of leishmaniasis.
4. Insecticides and repellents: evaluation of their efficacy.
5. Characterization of saliva proteins of hematophagous Diptera: genomics, proteomics, biochemistry and gene editing. Study of salivary proteins as markers of bite exposure, virulence factors and/or vaccines.
6. Xenodiagnosis of leishmaniasis.
7. Molecular biology and taxonomy of phlebotomine sand flies. Molecular detection of Leishmania infantum in phlebotomine sand flies and characterization of Leishmania spp. Molecular identification of blood ingested by vectors.
Research projects
Content with Investigacion .
CURRENT PROJECTS
Project title: "Biochemical and functional characterisation of salivary proteins of Phlebotomus perniciosus and their role in infection by Leishmania infantum (PERNIPROT)"Reference: Project PID2023-147773NA-I00 funded by MICIU/AEI/10.13039/501100011033 and by FEDER, EU.
Start date: 01/09/2024
End date: 31/08/2028
Funding: €175,000
Principal investigator: Inés Elena Martín Martín.
Funding agency: Agencia Estatal de Investigación (Proyecto de Generación del Conocimiento 2023).
Project title: "Surveillance of leishmaniasis in the Community of Madrid from a “One Health” perspective: study of the infectious capacity of patients with visceral leishmaniasis and their role as reservoirs"
Reference: PI24CIII/00026
Start date: 01/01/2025
End date: 31/12/2027
Funding: €60,000.00
Principal investigator: Inés Elena Martín Martín.
Co-principal investigator: Maribel Jiménez Alonso
Funding agency: Instituto de Salud Carlos III (Strategic Action in Intramural Health, AESI).
Service Contract: "Analysis for the surveillance of the vector and wild reservoirs that transmit leishmaniasis in the Community of Madrid"
Reference: file no. 17/2024 (A/SER-008455/2024).
Start date: 26/06/2024
End date: 10/12/25, extendable to 2026
Total funding: €171,084
Principal Investigator: Maribel Jiménez Alonso
Funding agency: Service Contract between the Instituto de Salud Carlos III and the Directorate-General for Public Health, Regional Ministry of Health of the Community of Madrid
Project Title: CIBERINFEC Research Group (CB21/13/00110)
Start date: 2021
End date: currently active
Principal Investigator: Dr. Mª Paz Sánchez-Seco, Arbovirus and Imported Viral Diseases Unit.
Researchers from the Medical Entomology Laboratory: Maribel Jiménez (member), Inés Martín Martín (collaborator).
Funding: €108,134. File number: CB21/13/00110.
Funding agency: Consortium Centre for Biomedical Research in NETWORK (CIBER)
PAST PROJECTS
Service Contract: "Evaluation of the anti-leishmania effect of the bacteria Tc1 and its derivatives in the intravectorial cycle"
Reference: ISCIII-06896
Start date: 15/12/2022
End date: 15/04/2025
Funding: €71,265.67
Principal Investigator: Inés Elena Martín Martín
Funding agency: Service Contract between the company GlaxoSmithKline R&D (GSK) and the Instituto de Salud Carlos III
Service Contract: "Analysis for the surveillance of the vector and wild reservoirs that transmit leishmaniasis in the Community of Madrid"
Reference: 59/2020 (A/SER-040739/2020)
Start date: 10/12/2021
End date: 10/12/2023.
Funding: €42,612.17 per year Total 2021-2023: €127,836.51
Principal Investigators: Ricardo Molina /Maribel Jiménez Alonso
Funding agency: Service contract between the Instituto de Salud Carlos III (ISCIII) and the Directorate-General for Public Health, Regional Ministry of Health of the Community of Madrid
Project title: "Research and Integrated Surveillance of Emerging Arboviruses West Nile, Toscana and Dengue in some areas of Spain"
Reference: PI19CIII/00014
Start date: 2020
End date: 2022
Principal Investigator: Ana Vázquez González
Co-Principal Investigator: Ricardo Molina
Funding: €60,000.00
Funding agency: Instituto de Salud Carlos III (Strategic Action in Intramural Health, AESI).
Project title: "Characterisation of the concept of ‘asymptomatic carrier’ in leishmaniasis: implications for treatment".
Start date: 01/01/2015
End date: 31/12/2017
Principal investigators: Javier Moreno and Javier García
Funding: €159,940
Funding agency: Study Agreement between Drugs for Neglected Diseases Initiative (DNDi), the Spanish Foundation for International Cooperation, Health and Social Policy (FCSAI) and Fuenlabrada Hospital. Subcontractor: ISCIII Medical Entomology Unit (Maribel Jiménez and Ricardo Molina).
Project title: "Biology and control of vector-borne infections in Europe (EDENext Collaborative Project): Sandfly-borne diseases".
Reference: Subproject (PBD) (EU, FP7-HEALTH-2010-single-stage, contract No. 261504).
Start date: 2011
End date: 2014
Principal investigator: Ricardo Molina General coordinator: Petr Volf
Funding: €140,000
Funding agency: EU-FP7
Project Title: "Phlebotomus perniciosus saliva as a source in the search for potential targets for the development of vaccines against Leishmania infantum"
Reference: AGL2008-01592/GAN (MICINN)
Start date: 2009
End date: 2011
Principal investigator: Ricardo Molina
Funding: €70,180
Funding agency: Ministry of Science and Innovation
Publications
Mycobacterium mageritense meningitis in an immunocompetent patient with an intrathecal catheter.
9. Muñoz-Sanz A, Rodríguez Vidigal FF, Vera-Tome A, Jimenez MS. Mycobacterium mageritense meningitis in an immunocompetent patient with an intrathecal catheter. Enfer Infecc Microbiol Clin. 2013; 31:59-6
PUBMED DOIMeasles virus genotype D4 strains with non-standard length M-F non-coding region circulated during the major outbreaks of 2011-2012 in Spain.
2. Gil H, Fernández-García A*, Mosquera MM, Hübschen JM, Castellanos AM, de Ory F, Masa-Calles J, Echevarría JE.Measles virus genotype D4 strains with non-standard length M-F non-coding region circulated during the major outbreaks of 2011-2012 in Spain. PLoS One. 2018 Jul. 16;13(7):e0199975. * Corresponding author.
PUBMED DOIIsolation, antigenicity and immunogenicity of Lleida Bat Lyssavirus
3. Banyard AC, Selden D, Wu G; Thorne L, Jennings D, Marston D, Finke S, Freuling CM, Mueller T, Echevarria JE, Fooks AR. Isolation, antigenicity and immunogenicity of Lleida Bat Lyssavirus. Journal of General Virology, 2018. 99(12):1590-1599
PUBMED DOIShift within age-groups of mumps incidence, hospitalizations and severe complications in a highly vaccinated population
6. López-Perea N, Masa-Callesa J, Torres de Miera MV, Fernández-García A, Echevarría JE, de Ory F, Martínez de Aragón MV. Shift within age-groups of mumps incidence, hospitalizations and severe complications in a highly vaccinated population. Spain, 1998–2014. Vaccine, 2017, 35(34): 4339-4345.
PUBMED DOIThe Complexity of Antibody Responses Elicited against the Respiratory Syncytial Virus Glycoproteins in Hospitalized Children Younger than 2 Years
2. Trento A, Rodriguez-Fernandez R, Gonzalez-Sanchez MI, Gonzalez-Martinez F, Mas V, Vazquez M, et al. The Complexity of Antibody Responses Elicited against the Respiratory Syncytial Virus Glycoproteins in Hospitalized Children Younger than 2 Years. Front Microbiol. 2017;8:2301.
PUBMED DOIPotent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state.
3. Rossey I, Gilman MS, Kabeche SC, Sedeyn K, Wrapp D, Kanekiyo M, et al. Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state. Nat Commun. 2017;8:14158.
PUBMED DOIRapid profiling of RSV antibody repertoires from the memory B cells of naturally infected adult donors
6. Gilman MS, Castellanos CA, Chen M, Ngwuta JO, Goodwin E, Moin SM, et al. Rapid profiling of RSV antibody repertoires from the memory B cells of naturally infected adult donors. Sci Immunol. 2016;1(6).
PUBMED DOICharacterization of a Prefusion-Specific Antibody That Recognizes a Quaternary, Cleavage-Dependent Epitope on the RSV Fusion Glycoprotein.
8. Gilman MS, Moin SM, Mas V, Chen M, Patel NK, Kramer K, et al. Characterization of a Prefusion-Specific Antibody That Recognizes a Quaternary, Cleavage-Dependent Epitope on the RSV Fusion Glycoprotein. PLoS Pathog. 2015;11(7):e1005035.
PUBMED DOIPolyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation.
9. Palomo C, Mas V, Vazquez M, Cano O, Luque D, Terron MC, et al. Polyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation. Virology. 2014;460-461:119-27.
PUBMED DOIBiophysical properties of single rotavirus particles account for the functions of protein shells in a multilayered virus
Jiménez-Zaragoza M., Yubero M.L., Martín-Forero E., Castón J.R., Reguera D., Luque D.*, de Pablo P.J., Rodríguez J.M. 2018. Biophysical properties of single rotavirus particles account for the functions of protein shells in a multilayered virus. eLife 7: e37295. *Corresponding author.
PUBMED DOIAcquisition of functions on the outer capsid surface during evolution of double-stranded RNA fungal viruses
Mata C.P., Luque D., Gómez-Blanco J., Rodríguez J.M., González J.M., Suzuki N., Ghabrial S.A., Carrascosa J.L., Trus B.L., Castón J.R. 2017. Acquisition of functions on the outer capsid surface during evolution of double-stranded RNA fungal viruses. PLoS Pathog. 13(12):e1006755.
PUBMED DOIStructural Insights into the Assembly and Regulation of Distinct Viral Capsid Complexes
Sarker S., C. Terrón M., Khandokar Y., Aragão D., Hardy J.M., Radjainia M., Jiménez-Zaragoza M., de Pablo P.J., Coulibaly F., Luque D., Raidal D.R., Forwood J.K. 2016. Structural Insights into the Assembly and Regulation of Distinct Viral Capsid Complexes. Nat. Commun. 7:13014. IF: 12.124; D1.
PUBMED DOIHeterodimers as the structural unit of the T=1 capsid of the fungal dsRNA Rosellinia necatrix quadrivirus 1
Luque D., Mata C.P., González-Camacho F., González J.M., Gómez-Blanco J., Alfonso C., Rivas G., Havens W.M., Kanematsu S., Suzuki N., Ghabrial S.A., Trus B.L., Castón J.R. 2016. Heterodimers as the structural unit of the T=1 capsid of the fungal dsRNA Rosellinia necatrix quadrivirus 1. J Virol. 90(24):11220-11230. IF: 4.666, Q1.
PUBMED DOISelf-assembly and characterization of small and monodisperse dye nanospheres in a protein cage
Luque D., de la Escosura A., Snijder J., Brasch M., Burnley R.J, Koay M.S.T., Carrascosa J.L., Wuite G.J.L., Roos W.H., Heck A.J.R., J.J.L.M Cornelissen, Torres T., Castón J.R. 2014. Self-assembly and characterization of small and monodisperse dye nanospheres in a protein cage. Chem. Sci.,5, 575-581. IF: 9.211, D1.
DOICryo-EM near-atomic structure of a dsRNA fungal virus shows ancient structural motifs preserved in the dsRNA viral lineage.
Luque D., Gómez-Blanco J., Garriga D., Brilot A.F., González J.M., Havens W.M., Carrascosa J.L., Trus B.L., Verdaguer N., Ghabrial S.A., Castón J.R. 2014. Cryo-EM near-atomic structure of a dsRNA fungal virus shows ancient structural motifs preserved in the dsRNA viral lineage. Proc Natl Acad Sci U S A 111(21):7641-7646. IF: 9.674, D1
PUBMED DOINew insights into rotavirus entry machinery: stabilization of rotavirus spike conformation is independent of trypsin cleavage
Rodríguez J.M., Chichón F.J., Martín-Forero E., González-Camacho F., Carrascosa J.L., Castón J.R., Luque D*. 2014. New insights into rotavirus entry machinery: stabilization of rotavirus spike conformation is independent of trypsin cleavage. PLoS Pathog. 10(5):e1004157. IF: 7.562, D1. * Corresponding autor.
PUBMED DOIContent with Investigacion .
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Horacio Gil Gil
Research Scientist
ORCID code: 0000-0002-7114-6686
Degree in Veterinary Medicine in 1995 and PhD in Veterinary Medicine in 2002 from the University of Zaragoza. He did his PhD thesis at NEIKER Tecknalia (Derio, Vizcaya) and the National Center for Microbiology of Instituto de Salud Carlos III (CNM-ISCIII, Majadahonda, Madrid) on the biological cycle of Lyme disease in the Basque Country. After that, he developed his postdoctoral training in different aspects of the pathogenesis of tularemia at the Center for Infectious Diseases, Stony Brook University, New York (USA) for 3 years. In December 2005, he joined the Reference and Research Laboratory in Special Pathogens of the CNM-ISCIII where he developed diagnostic, reference and research activities, in Bartonella, Leptospira and pathogens of interest in bioterrorism. Between 2014-2016 he participated in the European Program for the Training of Microbiologists in Public Health (EUPHEM), organized by the European Centre for Disease Prevention and Control. During this program, he participated in an international mission for the investigation of a cholera outbreak in Ghana, proposed by the Bernhard Nocht Institute for Tropical Diseases in Hamburg (Germany). In December 2016, he worked as a laboratory consultant for the World Health Organization at their office in Phnom Penh (Cambodia). Subsequently, he worked one year with Médecins Sans Frontières as director and quality manager of the TB laboratory in Nukus (Uzbekistan).
In 2019, he joined the HIV Variability and Biology Unit at CNM-ISCIII, where he developed different reference and research activities, including his contribution to the molecular epidemiological surveillance of HIV-1 in Spain and the study of HIV-1 antiretroviral resistance. Since September 2022 he has been leading the Human Papillomavirus Unit at the CNM-ISCIII. -
Alicia Inés García Señán
Predoctoral Student UNED
Degree in Pharmacy in 2013 from the Complutense University of Madrid. She completed specialized health training in Microbiology and Parasitology at the Complejo Asistencial Universitario de Salamanca (2014-2018). During this period he studied a master's degree in Tropical Diseases at the University of Salamanca (2016). She has developed her professional activity as a clinical microbiologist at the Hospital de Santa Bárbara (Soria) (2018), Hospital Universitario Vall d'Hebrón (Barcelona) (2019-2022), and Hospital Central de la Defensa (Gómez Ulla) C.S.V.E, since 2022. In September 2024 she has started PhD studies at the Human Papillomavirus Unit of the CNM-ISCIII.
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Manuela Rodríguez Vargas
Técnico de Laboratorio
List of staff
Additional Information
The research activity of the Viral Biology group since its beginnings in the 1980s has focused on respiratory viruses, especially on the study of the mechanisms of virus entry into the cell, evolutionary aspects, antigenic properties and vaccine development.
Currently, the group's objectives are focused on the characterisation of the immune response and the development of vaccines against human pneumoviruses: human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV).
Both viruses are considered to be important respiratory pathogens of high clinical relevance, especially in the paediatric population.
Safe and effective vaccines against these viruses are currently not available. Soluble protein subunits based on the fusion protein (F-protein) of hRSV and hMPV are being developed in the laboratory by protein engineering for use as vaccines against human pneumoviruses.
On the other hand, and thanks to the characterisation of the type of humoral response induced by the F proteins of these viruses, the laboratory is also involved in the isolation of monoclonal antibodies and nanoantibodies for use as treatments against these viruses.
The research activity of the Viral Biology group since its beginnings in the 1980s has focused on respiratory viruses, especially on the study of the mechanisms of virus entry into the cell, evolutionary aspects, antigenic properties and vaccine development.
Currently, the group's objectives are focused on the characterisation of the immune response and the development of vaccines against human pneumoviruses: human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV).
Both viruses are considered to be important respiratory pathogens of high clinical relevance, especially in the paediatric population.
Safe and effective vaccines against these viruses are currently not available. Soluble protein subunits based on the fusion protein (F-protein) of hRSV and hMPV are being developed in the laboratory by protein engineering for use as vaccines against human pneumoviruses.
On the other hand, and thanks to the characterisation of the type of humoral response induced by the F proteins of these viruses, the laboratory is also involved in the isolation of monoclonal antibodies and nanoantibodies for use as treatments against these viruses.