Hepatitis C virus fitness can influence the extent of infection-mediated epigenetic modifications in the host cells

Frontiers in Cellular and Infection Microbiology

Cellular and Infection Microbiology

Celia Perales¹  Javier García-Samaniego²  Irene Francisco-Recuero³  Marina Camblor-Murube³  Ana López-López³  Aurora Sánchez-Pacheco³  Carlos García-Crespo⁴  Isabel Gallego⁴  Esteban Domingo⁴  Ana Isabel de Ávila⁴  María Eugenia Soria⁵  Antonio Madejón⁶ 

[1] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain;Department of Clinical Microbiology, IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain;Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain;Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain;Hepatology Unit Hospital Universitario La Paz/Carlos III, Instituto de Investigación Sanitaria “La Paz”, Madrid, Spain;Department de Biochemistry, UAM, Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Madrid, Spain;Department of Interactions with the Environment, Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, Madrid, Spain;Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain;Department of Interactions with the Environment, Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, Madrid, Spain;Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain;Department of Clinical Microbiology, IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain;Department of Interactions with the Environment, Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, Madrid, Spain;Hepatology Unit Hospital Universitario La Paz/Carlos III, Instituto de Investigación Sanitaria “La Paz”, Madrid, Spain;

关键词: virus-host interaction;    histone modification;    viral quasispecies;    hepatocellular carcinoma;    viral fitness;    hepatitis C virus;    aurora kinase B;   

DOI  :  10.3389/fcimb.2023.1057082

 received in 2022-09-29, accepted in 2023-02-28,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionCellular epigenetic modifications occur in the course of viral infections. We previously documented that hepatitis C virus (HCV) infection of human hepatoma Huh-7.5 cells results in a core protein-mediated decrease of Aurora kinase B (AURKB) activity and phosphorylation of Serine 10 in histone H3 (H3Ser10ph) levels, with an affectation of inflammatory pathways. The possible role of HCV fitness in infection-derived cellular epigenetic modifications is not known.MethodsHere we approach this question using HCV populations that display a 2.3-fold increase in general fitness (infectious progeny production), and up to 45-fold increase of the exponential phase of intracellular viral growth rate, relative to the parental HCV population.ResultsWe show that infection resulted in a HCV fitness-dependent, average decrease of the levels of H3Ser10ph, AURKB, and histone H4 tri-methylated at Lysine 20 (H4K20m3) in the infected cell population. Remarkably, the decrease of H4K20m3, which is a hallmark of cellular transformation, was significant upon infection with high fitness HCV but not upon infection with basal fitness virus.DiscussionHere we propose two mechanisms ─which are not mutually exclusive─ to explain the effect of high viral fitness: an early advance in the number of infected cells, or larger number of replicating RNA molecules per cell. The implications of introducing HCV fitness as an influence in virus-host interactions, and for the course of liver disease, are warranted. Emphasis is made in the possibility that HCV-mediated hepatocellular carcinoma may be favoured by prolonged HCV infection of a human liver, a situation in which viral fitness is likely to increase.

【 授权许可】

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Copyright © 2023 García-Crespo, Francisco-Recuero, Gallego, Camblor-Murube, Soria, López-López, de Ávila, Madejón, García-Samaniego, Domingo, Sánchez-Pacheco and Perales