Related Experiment Video

Updated: Mar 13, 2026

LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring
08:45

LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring

Published on: November 17, 2018

14.2K

Nuclear receptors control pro-viral and antiviral metabolic responses to hepatitis C virus infection

Gahl Levy1,2, Naomi Habib1,1,3, Maria Angela Guzzardi1,4

  • 1Grass Center for Bioengineering, Benin School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.

Nature Chemical Biology
|October 11, 2016
PubMed

Insights

Hepatitis C virus hijacks host metabolism for replication. Inhibiting glycolysis hinders viral spread but increases cell death, revealing a complex host-pathogen metabolic interplay.

Area of Science:

  • Virology
  • Metabolic Engineering
  • Hepatology

Background:

  • Viruses rely on host cell metabolism for replication due to their inherent lack of machinery.
  • Understanding virus-induced metabolic alterations is crucial for deciphering host-pathogen interactions.
  • Host transcriptional regulation of metabolism during viral infection remains understudied.

Purpose of the Study:

  • To systematically investigate hepatitis C virus (HCV)-driven metabolic changes in human hepatocytes.
  • To identify nuclear receptors regulating host metabolism in response to HCV infection.
  • To explore the therapeutic potential of targeting host metabolic pathways.

Main Methods:

  • System-wide metabolic flux analysis in primary human hepatocytes.
  • Targeted perturbation of nuclear receptors (HNF4α, PPARα, FXR, PXR).
  • Pharmaceutical inhibition of key metabolic regulators.

Main Results:

  • HCV infection upregulated glycolysis, ketogenesis, and drug metabolism.
  • HNF4α activation controlled glycolysis; PPARα and FXR controlled ketogenesis; PXR controlled drug metabolism.
  • Inhibiting HNF4α reduced viral replication but increased apoptosis; inhibiting PPARα/FXR increased viral replication, indicating a host antiviral response.

Conclusions:

  • HCV infection profoundly alters host cell metabolism.
  • Targeting host metabolic pathways presents a complex therapeutic landscape with potential benefits and drawbacks.
  • Host metabolic reprogramming during viral infection can elicit antiviral defense mechanisms.

More Related Videos

A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target11:34

A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target

Published on: May 10, 2022

2.7K
Modeling Hepatitis B Virus Infection in Non-Hepatic 293T-NE-3NRs Cells09:02

Modeling Hepatitis B Virus Infection in Non-Hepatic 293T-NE-3NRs Cells

Published on: June 5, 2020

8.0K

Related Concept Videos

Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
4.6K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.4K
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
Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
2.4K
Signal Transduction: Overview01:26

Signal Transduction: Overview

Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
12.3K
Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
7.1K