Related Experiment Video

Updated: Feb 6, 2026

Mutagenesis and Functional Analysis of Ion Channels Heterologously Expressed in Mammalian Cells
15:28

Mutagenesis and Functional Analysis of Ion Channels Heterologously Expressed in Mammalian Cells

Published on: October 1, 2010

18.0K

Alkyl-imino sugars inhibit the pro-oncogenic ion channel function of human papillomavirus (HPV) E5

Laura F Wetherill1, Christopher W Wasson2, Gemma Swinscoe2

  • 1School of Molecular and Cellular Biology, Faculty of Biological Sciences, UK; School of Medicine, Faculty of Medicine & Health, University of Leeds, Wellcome Trust Brenner Building, St James' University Hospital, Beckett St., Leeds, LS9 7TF, UK; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.

Antiviral Research
|August 11, 2018
PubMed

Insights

New antiviral therapies targeting the human papillomavirus (HPV) E5 oncoprotein show promise. Imino sugars and rimantadine inhibit E5 viroporin activity, blocking cancer-driving signaling pathways.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • Human papillomavirus (HPV) infection is a major cause of cancer, and current vaccines do not offer complete protection.
  • The HPV E5 oncoprotein forms a viroporin channel, a potential therapeutic target.
  • Previous work identified rimantadine as an inhibitor of the E5 ion channel.

Purpose of the Study:

  • To investigate the antiviral potential of imino sugars against HPV E5 viroporin.
  • To explore the mechanism of imino sugar inhibition of E5 channel activity.
  • To evaluate the efficacy of viroporin inhibitors in blocking HPV-mediated oncogenic signaling.

Main Methods:

  • In vitro inhibition assays of E5 channel activity by imino sugars.
  • Molecular modeling to predict imino sugar-E5 interaction.
  • Assessment of ERK-MAPK phosphorylation and cyclin B1 expression in HPV-infected keratinocytes treated with inhibitors.

Main Results:

  • Alkylated imino sugars inhibited E5 viroporin channel activity in vitro.
  • Molecular modeling suggested imino sugars disrupt E5 protomer oligomerization.
  • Rimantadine and imino sugars reduced ERK-MAPK phosphorylation and cyclin B1 expression in keratinocytes expressing high-risk HPV E5.
  • Viroporin inhibitors demonstrated efficacy in primary human keratinocytes infected with HPV18.

Conclusions:

  • The HPV E5 oncoprotein functions as a viroporin critical for the viral life cycle.
  • Viroporin inhibitors, including imino sugars and rimantadine, represent a potential therapeutic strategy for HPV-associated malignancies.
  • These inhibitors could be used for stratified treatment of tumors or as antiviral agents to prevent malignant transformation.
Keywords:
EGFR signallingHPVViroporin

More Related Videos

Author Spotlight: Exploring the Role of Ion Channels in Cancer: Characterization and Potential Treatment Approaches06:19

Author Spotlight: Exploring the Role of Ion Channels in Cancer: Characterization and Potential Treatment Approaches

Published on: June 16, 2023

3.9K
Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus13:41

Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus

Published on: March 8, 2012

13.0K

Related Concept Videos

Ion Channels01:19

Ion Channels

The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
Ion channels are specialized integral membrane proteins on the plasma membrane that allow...
91.5K
Non-gated Ion Channels01:24

Non-gated Ion Channels

Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism....
8.3K
α-Alkylation of Ketones via Enolate Ions01:10

α-Alkylation of Ketones via Enolate Ions

Ketones with α protons are deprotonated by strong bases like lithium diisopropylamide (LDA) to form enolate ions. The anion is stabilized by resonance, and its hybrid structure exhibits negative charges on the carbonyl oxygen and the α carbon. This ambident nucleophile can attack an electrophile via two possible sites: the carbonyl oxygen, known as O-attack, or the α carbon, known as C-attack. The nucleophilic attack via the carbanionic site is preferred. This is due to the...
3.9K
Mechanically-gated Ion Channels01:12

Mechanically-gated Ion Channels

Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
7.8K
Ligand-gated Ion Channels01:19

Ligand-gated Ion Channels

Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
14.4K
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
5.7K