In:
Liver International, Wiley, Vol. 37, No. 5 ( 2017-05), p. 669-677
Abstract:
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 JFH 1 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/ JFH 1 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/ JFH 1 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.
Type of Medium:
Online Resource
ISSN:
1478-3223
,
1478-3231
DOI:
10.1111/liv.2017.37.issue-5
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
2124684-1
