Inflammatory response in liver disease

GROUP INFORMATION

Hepatotropic viruses, including hepatitis C virus (HCV), chronically infect millions of people worldwide. Infection can lead to fibrosis, cirrhosis and hepatocellular carcinoma, and is the leading cause of liver transplantation. The current standard therapeutic procedure against chronic hepatitis C, pegylated IFN-alpha in combination with ribavirin and HCV NS3/4ª, protease inhibitor, is often ineffective depending on viral and host factors.

Our group is interested in understanding how HCV interacts with target cells, with special emphasis on the role of cellular factors involved in the different stages of the virus life cycle, including entry, assembly, exit and dissemination. Studies published by the group have recently determined that HCV output is a clathrin-dependent process. We are studying: 1) factors involved in HCV entry in highly polarised cultures; 2) the role of apolipoproteins in HCV dissemination; 3) changes in the hepatocyte proteome following HCV infection. Finally, we are also exploring if therapies based on dendrimers could be used to inhibit HCV infection.

Globally, these studies could provide new insights into our knowledge of virus-host interactions and the molecular mechanisms underlying the pathogenesis of progressive liver diseases related to hepatotropic viruses. We believe that this ambitious project could identify new molecular targets involved in HCV infection and could improve the management of patients with chronic infection.

Team members
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Group leader:

Pedro Lorenzo Majano Rodríguez

Hospital Universitario La Princesa

  Other team members:

 

  • Sergio Casanova Francés. Hospital Universitario La Princesa.
  • Jennifer Fernández Pacheco. Hospital Universitario La Princesa.
  • Raquel Herranz Pérez. Hospital Universitario La Princesa.
  • Verónica Martín Domínguez. Hospital Universitario La Princesa.
  • Pablo Miranda García. Hospital Universitario La Princesa.
  • Francisca Molina Jiménez. Hospital Universitario La Princesa.
  • Felipe de la Morena López. Hospital Universitario La Princesa.
  • José Andrés Moreno Monteagudo. Hospital Universitario La Princesa.
  • María Teresa Pérez Fernández. Hospital Universitario La Princesa.
  • Cecilio Santander Vaquero. Hospital Universitario La Princesa.

Majano Rodríguez, Pedro Lorenzo. Estudio de la interacción entre el virus de la hepatitis C y sus células diana: papel del “microambiente hepático”, la asociación con lipoproteínas y el modo de diseminación en distintas fases del ciclo viral. PI13/00159. ISCIII. 2014-2016.

Majano Rodríguez, Pedro Lorenzo. Esofagitis eosinofílica: estudios en biopsia esofágica y sangre periférica para la identificación de biomarcadores de la enfermedad y de la respuesta al tratamiento. PI17/00008. ISCIII. 2018-2020.

This grant is funded by the 2013-2016 Spanish Science, Technology and Innovation Research Plan and the ISCIII – Subdirectorate General for Evaluation and Promotion of Research – and co-financed by the European Regional Development Fund, Operational Programme Smart Growth 2014-2020 according to Regulation (EU) no. 1303/2013.

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Benedicto I, Gondar V, Molina-Jiménez F, García-Buey L, López-Cabrera M, Gastaminza P, Majano PL. Clathrin mediates infectious hepatitis C virus particle egress. J Virol 2015. 89: 4180-4190. FI: 4.439(Q1). PMID: 25631092. DOI: 10.1128/JVI.03620-14.

Reglero-Real N, Alvarez-Varela A, Cernuda-Morollón E, Feito J, Marcos-Ramiro B, Fernández-Martín L, Gómez-Lechón MJ, Muntané J, Sandoval P, Majano PL, Correas I, Alonso MA, Millán J. Apicobasal Polarity Controls Lymphocyte Adhesion to Hepatic Epithelial Cells. Cell Reports 2014. 8: 1879-1893. FI: 8.358(Q1). PMID: 25242329. DOI: 10.1016/j.celrep.2014.08.007.

Molina-Jimenez F, Benedicto I, Dao Thi VL, Gondar V, Lavillette D, Marin JJ, Briz O, Moreno-Otero R, Aldabe R, Baumert TF, Cosset FL, Lopez-Cabrera M, Majano PL. Matrigel-embedded 3D culture of Huh-7 cells as a hepatocyte-like polarized system to study hepatitis C virus cycle. VIROLOGY 2012. 425: 31-39. FI: 3.367(Q2). PMID: 22280897. DOI: 10.1016/j.virol.2011.12.021.

Benedicto, Ignacio, Molina-Jimenez, Francisca, Moreno-Otero, Ricardo, Lopez-Cabrera, Manuel, Majano, Pedro L. Interplay among cellular polarization, lipoprotein metabolism and hepatitis C virus entry. World J Gastroenterol 2011. 17: 2683-2690. FI: 2.471(Q2). PMID: 21734774. DOI: 10.3748/wjg.v17.i22.2683.

Molina-Jiménez F, Benedicto I, Murata M, Martín-Vílchez S, Seki T, Antonio Pintor-Toro J, Tortolero M, Moreno-Otero R, Okazaki K, Koike K, Barbero JL, Matsuzaki K, Majano PL, López-Cabrera M. Expression of Pituitary Tumor-Transforming Gene 1 (PTTG1)/Securin in Hepatitis B Virus (HBV)-Associated Liver Diseases: Evidence for an HBV X Protein-Mediated Inhibition of PTTG1 Ubiquitination and Degradation. Hepatology 2010. 51: 777-787. FI: 10.885(Q1). PMID: 20198633. DOI: 10.1002/hep.23468.