Hepatitis C virus fitness can influence the extent of infection-mediated epigenetic modifications in the host cells
Copyright © 2023 García-Crespo, Francisco-Recuero, Gallego, Camblor-Murube, Soria, López-López, de Ávila, Madejón, García-Samaniego, Domingo, Sánchez-Pacheco and Perales..
Introduction: Cellular 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.
Methods: Here 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.
Results: We 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.
Discussion: Here 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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
|---|---|
| Enthalten in: |
Frontiers in cellular and infection microbiology - 13(2023) vom: 29., Seite 1057082 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
García-Crespo, Carlos [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Aurora kinase B |
|---|
| Anmerkungen: |
Date Completed 31.03.2023 Date Revised 07.04.2023 published: Electronic-eCollection Citation Status MEDLINE |
|---|
| doi: |
10.3389/fcimb.2023.1057082 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM35497629X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM35497629X | ||
| 003 | DE-627 | ||
| 005 | 20231226063357.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3389/fcimb.2023.1057082 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1183.xml |
| 035 | |a (DE-627)NLM35497629X | ||
| 035 | |a (NLM)36992689 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a García-Crespo, Carlos |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Hepatitis C virus fitness can influence the extent of infection-mediated epigenetic modifications in the host cells |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 31.03.2023 | ||
| 500 | |a Date Revised 07.04.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 García-Crespo, Francisco-Recuero, Gallego, Camblor-Murube, Soria, López-López, de Ávila, Madejón, García-Samaniego, Domingo, Sánchez-Pacheco and Perales. | ||
| 520 | |a Introduction: Cellular 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 | ||
| 520 | |a Methods: Here 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 | ||
| 520 | |a Results: We 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 | ||
| 520 | |a Discussion: Here 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a aurora kinase B | |
| 650 | 4 | |a hepatitis C virus | |
| 650 | 4 | |a hepatocellular carcinoma | |
| 650 | 4 | |a histone modification | |
| 650 | 4 | |a viral fitness | |
| 650 | 4 | |a viral quasispecies | |
| 650 | 4 | |a virus-host interaction | |
| 700 | 1 | |a Francisco-Recuero, Irene |e verfasserin |4 aut | |
| 700 | 1 | |a Gallego, Isabel |e verfasserin |4 aut | |
| 700 | 1 | |a Camblor-Murube, Marina |e verfasserin |4 aut | |
| 700 | 1 | |a Soria, María Eugenia |e verfasserin |4 aut | |
| 700 | 1 | |a López-López, Ana |e verfasserin |4 aut | |
| 700 | 1 | |a de Ávila, Ana Isabel |e verfasserin |4 aut | |
| 700 | 1 | |a Madejón, Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a García-Samaniego, Javier |e verfasserin |4 aut | |
| 700 | 1 | |a Domingo, Esteban |e verfasserin |4 aut | |
| 700 | 1 | |a Sánchez-Pacheco, Aurora |e verfasserin |4 aut | |
| 700 | 1 | |a Perales, Celia |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Frontiers in cellular and infection microbiology |d 2011 |g 13(2023) vom: 29., Seite 1057082 |w (DE-627)NLM220414289 |x 2235-2988 |7 nnns |
| 773 | 1 | 8 | |g volume:13 |g year:2023 |g day:29 |g pages:1057082 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3389/fcimb.2023.1057082 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 13 |j 2023 |b 29 |h 1057082 | ||