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17,β‐estradiol inhibits hepatitis C virus mainly by interference with the release phase of its life cycle

BACKGROUND & AIMS: Oestrogen and oestrogen‐mediated signalling protect from hepatitis C virus through incompletely understood mechanisms. We aimed to ascertain which phase(s) of hepatitis C virus life cycle is/are affected by oestrogens. METHODS: Huh7 cells infected with the JFH1 virus (genotype...

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Autores principales: Magri, Andrea, Barbaglia, Matteo N., Foglia, Chiara Z., Boccato, Elisa, Burlone, Michela E., Cole, Sarah, Giarda, Paola, Grossini, Elena, Patel, Arvind H., Minisini, Rosalba, Pirisi, Mario
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5448036/
https://www.ncbi.nlm.nih.gov/pubmed/27885811
http://dx.doi.org/10.1111/liv.13303
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author Magri, Andrea
Barbaglia, Matteo N.
Foglia, Chiara Z.
Boccato, Elisa
Burlone, Michela E.
Cole, Sarah
Giarda, Paola
Grossini, Elena
Patel, Arvind H.
Minisini, Rosalba
Pirisi, Mario
author_facet Magri, Andrea
Barbaglia, Matteo N.
Foglia, Chiara Z.
Boccato, Elisa
Burlone, Michela E.
Cole, Sarah
Giarda, Paola
Grossini, Elena
Patel, Arvind H.
Minisini, Rosalba
Pirisi, Mario
author_sort Magri, Andrea
collection PubMed
description BACKGROUND & AIMS: Oestrogen and oestrogen‐mediated signalling protect from hepatitis C virus through incompletely understood mechanisms. We aimed to ascertain which phase(s) of hepatitis C virus life cycle is/are affected by oestrogens. METHODS: Huh7 cells infected with the JFH1 virus (genotype 2a) were exposed to dehydroepiandrosterone, testosterone, progesterone and 17β‐estradiol (tested with/without its receptor antagonist fulvestrant). Dose–response curves were established to calculate half maximal inhibitory concentration values. To dissect how 17β‐estradiol interferes with phases of hepatitis C virus life cycle, its effects were measured on the hepatitis C virus pseudo‐particle system (viral entry), the subgenomic replicon N17/JFH1 and the replicon cell line Huh7‐J17 (viral replication). Finally, in a dual‐step infection model, infectious supernatants, collected from infected cells exposed to hormones, were used to infect naïve cells. RESULTS: Progesterone and testosterone showed no inhibitory effect on hepatitis C virus; dehydroepiandrosterone was only mildly inhibitory. In contrast, 17β‐estradiol inhibited infection by 64%‐67% (IC (50) values 140‐160 nmol/L). Fulvestrant reverted the inhibition by 17β‐estradiol in a dose‐dependent manner. 17β‐estradiol exerted only a slight inhibition (<20%) on hepatitis C virus pseudo‐particles, and had no effect on cells either transiently or stably (Huh7‐J17 cells) expressing the N17/JFH1 replicon. In the dual‐step infection model, a significant half maximal inhibitory concentration decline occurred between primary (134 nmol/L) and secondary (100 nmol/L) infections (P=.02), with extracellular hepatitis C virus RNA and infectivity being reduced to a higher degree in comparison to its intracellular counterpart. CONCLUSIONS: 17β‐estradiol inhibits hepatitis C virus acting through its intracellular receptors, mainly interfering with late phases (assembly/release) of the hepatitis C virus life cycle.
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spelling pubmed-54480362017-05-31 17,β‐estradiol inhibits hepatitis C virus mainly by interference with the release phase of its life cycle Magri, Andrea Barbaglia, Matteo N. Foglia, Chiara Z. Boccato, Elisa Burlone, Michela E. Cole, Sarah Giarda, Paola Grossini, Elena Patel, Arvind H. Minisini, Rosalba Pirisi, Mario Liver Int Viral Hepatitis BACKGROUND & AIMS: Oestrogen and oestrogen‐mediated signalling protect from hepatitis C virus through incompletely understood mechanisms. We aimed to ascertain which phase(s) of hepatitis C virus life cycle is/are affected by oestrogens. METHODS: Huh7 cells infected with the JFH1 virus (genotype 2a) were exposed to dehydroepiandrosterone, testosterone, progesterone and 17β‐estradiol (tested with/without its receptor antagonist fulvestrant). Dose–response curves were established to calculate half maximal inhibitory concentration values. To dissect how 17β‐estradiol interferes with phases of hepatitis C virus life cycle, its effects were measured on the hepatitis C virus pseudo‐particle system (viral entry), the subgenomic replicon N17/JFH1 and the replicon cell line Huh7‐J17 (viral replication). Finally, in a dual‐step infection model, infectious supernatants, collected from infected cells exposed to hormones, were used to infect naïve cells. RESULTS: Progesterone and testosterone showed no inhibitory effect on hepatitis C virus; dehydroepiandrosterone was only mildly inhibitory. In contrast, 17β‐estradiol inhibited infection by 64%‐67% (IC (50) values 140‐160 nmol/L). Fulvestrant reverted the inhibition by 17β‐estradiol in a dose‐dependent manner. 17β‐estradiol exerted only a slight inhibition (<20%) on hepatitis C virus pseudo‐particles, and had no effect on cells either transiently or stably (Huh7‐J17 cells) expressing the N17/JFH1 replicon. In the dual‐step infection model, a significant half maximal inhibitory concentration decline occurred between primary (134 nmol/L) and secondary (100 nmol/L) infections (P=.02), with extracellular hepatitis C virus RNA and infectivity being reduced to a higher degree in comparison to its intracellular counterpart. CONCLUSIONS: 17β‐estradiol inhibits hepatitis C virus acting through its intracellular receptors, mainly interfering with late phases (assembly/release) of the hepatitis C virus life cycle. John Wiley and Sons Inc. 2016-11-25 2017-05 /pmc/articles/PMC5448036/ /pubmed/27885811 http://dx.doi.org/10.1111/liv.13303 Text en © 2016 The Authors. Liver International Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Viral Hepatitis
Magri, Andrea
Barbaglia, Matteo N.
Foglia, Chiara Z.
Boccato, Elisa
Burlone, Michela E.
Cole, Sarah
Giarda, Paola
Grossini, Elena
Patel, Arvind H.
Minisini, Rosalba
Pirisi, Mario
17,β‐estradiol inhibits hepatitis C virus mainly by interference with the release phase of its life cycle
title 17,β‐estradiol inhibits hepatitis C virus mainly by interference with the release phase of its life cycle
title_full 17,β‐estradiol inhibits hepatitis C virus mainly by interference with the release phase of its life cycle
title_fullStr 17,β‐estradiol inhibits hepatitis C virus mainly by interference with the release phase of its life cycle
title_full_unstemmed 17,β‐estradiol inhibits hepatitis C virus mainly by interference with the release phase of its life cycle
title_short 17,β‐estradiol inhibits hepatitis C virus mainly by interference with the release phase of its life cycle
title_sort 17,β‐estradiol inhibits hepatitis c virus mainly by interference with the release phase of its life cycle
topic Viral Hepatitis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5448036/
https://www.ncbi.nlm.nih.gov/pubmed/27885811
http://dx.doi.org/10.1111/liv.13303
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