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

Andrea Magri1,2, Matteo N Barbaglia1, Chiara Z Foglia1

  • 1Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy.

Abstract

Insights

17β-estradiol significantly inhibits hepatitis C virus (HCV) infection by targeting its intracellular receptors. This estrogen primarily interferes with the late stages of the HCV life cycle, including assembly and release.

Area of Science:

  • Hepatology
  • Virology
  • Endocrinology

Background:

  • Oestrogen and oestrogen-mediated signalling are known to protect against hepatitis C virus (HCV) infection.
  • The precise mechanisms by which oestrogens exert their protective effects remain incompletely understood.

Purpose of the Study:

  • To investigate which specific phases of the hepatitis C virus (HCV) life cycle are affected by oestrogens.
  • To elucidate the role of 17β-estradiol in modulating HCV infection.

Main Methods:

  • Huh7 cells infected with JFH1 virus (genotype 2a) were treated with various hormones, including 17β-estradiol, and its effects on viral entry, replication, and release were assessed.
  • Dose-response curves were used to determine half maximal inhibitory concentration (IC50) values.
  • A dual-step infection model was employed to evaluate the impact of 17β-estradiol on both primary and secondary HCV infections.

Main Results:

  • 17β-estradiol demonstrated significant inhibition of HCV infection (64%-67%), with IC50 values ranging from 140-160 nmol/L.
  • The inhibitory effect of 17β-estradiol was dose-dependently reversed by the receptor antagonist fulvestrant.
  • 17β-estradiol had minimal impact on viral entry and replication but significantly reduced extracellular HCV RNA and infectivity, particularly in secondary infections.

Conclusions:

  • 17β-estradiol inhibits hepatitis C virus (HCV) infection by acting through intracellular receptors.
  • The primary mechanism of inhibition involves interference with the late stages of the HCV life cycle, specifically viral assembly and release.
  • These findings highlight a potential therapeutic role for oestrogen-based therapies in managing HCV infection.

Related Concept Videos

Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow

Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug...
307
Hepatic Drug Excretion: Enterohepatic Cycling01:17

Hepatic Drug Excretion: Enterohepatic Cycling

Enterohepatic cycling involves the active secretion of drugs and their metabolites into the bile via transporters in the canalicular membrane of hepatocytes. This secretion is an integral part of the digestive process, releasing these substances into the gastrointestinal (GI) tract.
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...
3.2K
Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment01:08

Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment

Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
320
Viruses with RNA Genomes01:29

Viruses with RNA Genomes

RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
1.2K
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test01:22

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test

In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess...
247
Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug01:14

Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug

In pharmacotherapy, monitoring drug concentrations is paramount, especially for drugs whose therapeutic effects hinge on both the active compound and its metabolite. Hepatic impairment profoundly influences drug potency by altering liver function. If the drug is more potent than its metabolite, impaired liver function amplifies drug activity due to elevated drug concentration levels. Conversely, if the metabolite holds greater potency, diminished liver function diminishes drug activity by...
274