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Investigation

Toxoplasmosis and intestinal protozoa

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

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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.

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Publications

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Influenza vaccine effectiveness in Spain 2013/14: subtype-specific early estimates using the cycEVA study

Jiménez-Jorge S, Pozo F, de Mateo S, Delgado-Sanz C, Casas I, García-Cenoz M, Castilla J, Sancho R, Etxebarriarteun-Aranzabal L, Quinones C, Martínez E, Vega T, Garcia A, Giménez J, Vanrell JM, Castrillejo D, Larrauri A, on behalf of the Spanish Influenza Sentinel Surveillance System (SISS). Influenza vaccine effectiveness in Spain 2013/14: subtype-specific early estimates using the cycEVA study. Euro Surveill. 2014 Mar 6;19(9). Indice Impacto: 5,722. Revista en Q1.

PUBMED DOI

Y155H amino acid substitution in influenza A(H1N1)pdm09 viruses does not confer a phenotype of reduced susceptibility to neuraminidase inhibitors

Perez-Sautu U, Pozo F, Cuesta I, Monzon S, Calderon A, Gonzalez M, Molinero M, Lopez-Miragaya I, Rey S, Cañizares A, Rodriguez G, Gonzalez-Velasco C, Lackenby A, Casas I. Y155H amino acid substitution in influenza A(H1N1)pdm09 viruses does not confer a phenotype of reduced susceptibility to neuraminidase inhibitors. Euro Surveill. 2014 Jul 10;19(27):14-20. Indice Impacto: 5,722. Revista en Q1

PUBMED DOI

Characterization In Vitro and In Vivo of a Pandemic H1N1 Influenza Virus from a Fatal Case.

Rodriguez A, Falcon A, Cuevas MT, Pozo F, Guerra S, García-Barreno B, Martinez-Orellana P, Pérez-Breña P, Montoya M, Melero JA, Pizarro M, Ortin J, Casas I, Nieto A. Characterization In Vitro and In Vivo of a Pandemic H1N1 Influenza Virus from a Fatal Case. PLoS One. 2013;8(1):e53515. doi: 10.1371/journal.pone.0053515. Epub 2013 Jan 10. Indice Impacto: 3,534. Revista en Q1

PUBMED DOI

Prospective study of influenza C in hospitalized children.

Calvo C, García-García ML, Borrell B, Pozo F, Casas I. Prospective study of influenza C in hospitalized children. Pediatr Infect Dis J. 2013 Aug;32(8):916-9. doi: 10.1097/INF.0b013e31828fca10. Indice Impacto: 3,135. Revista en Q1

PUBMED DOI

Disseminated Infection due to Mycobacterium chimaera after aortic valve replacement.

Gasch O, Meije Y, Espasa M, Font B, Jimenez MS, Fernandez-Hidalgo N. Disseminated Infection due to Mycobacterium chimaera after aortic valve replacement. Rev Esp Cardiol. 2018. Jul

PUBMED DOI

Mycobacterium tuberculosis genotypes and predominant clones among the multidrug-resistant isolates in Spain 1998-2006

3. Samper S, Gavin P, Millan-Lou MI, Iglesias M.J. Jimenez MS. Spanish Working Group on MDR-TB, Covin D, Rastogi N. Mycobacterium tuberculosis genotypes and predominant clones among the multidrug-resistant isolates in Spain 1998-2006. Infec Genet Evol. 2017. Aug 5;55:117.

PUBMED DOI

Antitubercular drugs for an old target: GSK693 as a promising inhA direct inhibitor.

5. Martinez-Hoyos M, Perez-Herran E, Gulten G, Encinas L, Alvarez-Gomez D, Alvarez E, Ferrer Bazaga S, Garcia-Perez A, Ortega F, Angulo-Bartures I, Rullas-Trincado J, Blanco Ruano D, Torres P, Castañeda P, Huss S, Fernandez R, Gonzalez del Valle S, Ballel L, Barros D, Modha S, Dhar N, Signorino-Gelo F, McKinney JD, Garcia-Bustos JF, Lavandera JL, Sacchettini JC, Jimenez MS, Martin-Casabona N, Castro-PIchel J, Mendoza-Losana A. Antitubercular drugs for an old target: GSK693 as a promising inhA direct inhibitor. EBioMedicine. 2016; 8:291-301

PUBMED DOI

Peritoneal tuberculosis due to Mycobacterium caprae.

6. Nebreda T, Alvarez-Prida E, Blanco B, Remacha MS, Samper S, Jimenez MS. Peritoneal tuberculosis due to Mycobacterium caprae. ID Cases 2016; 4:50-52.

PUBMED DOI

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List of staff

Additional Information

Our group carries out research studies in the diagnosis, reference and epidemiology of zoonoses and emerging diseases, both indigenous and imported, caused by protozoa. Coordinates the study in the human field with the relevance of the animal field and the environment (One Health initiative), with special interest in Toxoplasmosis, a highly prevalent zoonosis (WHO lists it as the 3rd food-borne zoonosis in Europe), presents a complex epidemiological cycle and causes neurological, ocular and systemic symptoms. We carry out diagnostic and characterization studies of Toxoplasma gondii from human and animal cases, to obtain greater epidemiological information and analyze the possible relationship with virulence and pathology.

Cryptosporidium, Giardia, Blastocystis and Entamoeba histolytica cause gastrointestinal diseases, affecting children, immunosuppressed people and travelers. They can cause outbreaks.  We develop diagnostic and characterization studies of isolates from humans and animals, from different areas and countries, to establish the presence of the main species and genotypes and the epidemiological situation. We are beginning the study of associations between these parasites and the intestinal microbiota.

The pathogenic Free-Living Amoebas, Acanthamoeba, Naegleria fowleri and Balamuthia mandrillaris, cause emerging diseases, highlighting the importance of the environment in transmission. They cause underdiagnosed neurological and ocular cases. The diagnostic and genotyping study of human and animal isolates that we are carrying out aims to establish the real prevalence, transmission routes and epidemiology.

Our group carries out research studies in the diagnosis, reference and epidemiology of zoonoses and emerging diseases, both indigenous and imported, caused by protozoa. Coordinates the study in the human field with the relevance of the animal field and the environment (One Health initiative), with special interest in Toxoplasmosis, a highly prevalent zoonosis (WHO lists it as the 3rd food-borne zoonosis in Europe), presents a complex epidemiological cycle and causes neurological, ocular and systemic symptoms. We carry out diagnostic and characterization studies of Toxoplasma gondii from human and animal cases, to obtain greater epidemiological information and analyze the possible relationship with virulence and pathology.

Cryptosporidium, Giardia, Blastocystis and Entamoeba histolytica cause gastrointestinal diseases, affecting children, immunosuppressed people and travelers. They can cause outbreaks.  We develop diagnostic and characterization studies of isolates from humans and animals, from different areas and countries, to establish the presence of the main species and genotypes and the epidemiological situation. We are beginning the study of associations between these parasites and the intestinal microbiota.

The pathogenic Free-Living Amoebas, Acanthamoeba, Naegleria fowleri and Balamuthia mandrillaris, cause emerging diseases, highlighting the importance of the environment in transmission. They cause underdiagnosed neurological and ocular cases. The diagnostic and genotyping study of human and animal isolates that we are carrying out aims to establish the real prevalence, transmission routes and epidemiology.

Content with Investigacion Virología Molecular .