Related Experiment Video

Updated: Aug 9, 2026

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
08:32

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Published on: March 2, 2014

Involvement of p38 signaling pathway in interferon-alpha-mediated antiviral activity toward hepatitis C virus

Hisashi Ishida1, Kazuyoshi Ohkawa, Atsushi Hosui

  • 1Department of Molecular Therapeutics, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.

Biochemical and Biophysical Research Communications
|September 11, 2004
PubMed

Insights

The p38-MK2 signaling pathway is crucial for interferon-alpha

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Hepatitis C virus (HCV) infection poses a significant global health challenge.
  • Interferon-alpha (IFN-alpha) is a key antiviral cytokine used in HCV treatment.
  • The precise molecular mechanisms underlying IFN-alpha's anti-HCV activity require further elucidation.

Purpose of the Study:

  • To investigate the role of the p38 signaling pathway in IFN-alpha's antiviral effects against HCV.
  • To determine if the p38 pathway's involvement is independent of the Janus kinase-STAT signaling cascade.

Main Methods:

  • Utilized HCV subgenomic replicon cells for in vitro studies.
  • Administered IFN-alpha with and without p38 pathway inhibitors.
  • Assessed the impact on viral RNA replication.
  • Monitored STAT1 phosphorylation and interferon stimulatory response element (ISRE) gene expression.

Main Results:

  • IFN-alpha's suppression of HCV replicon RNA was reduced when p38 was inhibited.
  • p38 inhibition minimally affected STAT1 phosphorylation and ISRE-dependent gene induction by IFN-alpha.
  • Inhibition of mitogen-activated protein kinase-activated protein kinase 2 (MK2) mirrored the effects of p38 inhibition on anti-HCV activity.

Conclusions:

  • The p38 signaling pathway, potentially via MK2, contributes significantly to IFN-alpha's antiviral activity against HCV.
  • This p38-MK2 mediated anti-HCV effect appears to operate independently of the canonical Janus kinase-STAT pathway.

More Related Videos

Immunofluorescence to Monitor the Cellular Uptake of Human Lactoferrin and its Associated Antiviral Activity Against the Hepatitis C Virus06:28

Immunofluorescence to Monitor the Cellular Uptake of Human Lactoferrin and its Associated Antiviral Activity Against the Hepatitis C Virus

Published on: October 1, 2015

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF311:44

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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...
Hepatitis01:25

Hepatitis

Hepatitis is an inflammatory condition of the liver most commonly caused by hepatotropic viruses (A–E), though non-infectious causes such as alcohol and drugs also exist.Hepatitis AHepatitis A virus (HAV) is a non-enveloped RNA virus of the Picornaviridae family. It is primarily transmitted via the fecal-oral route, typically through ingestion of contaminated food or water. After ingestion, HAV enters the bloodstream through the oropharynx or intestinal epithelium and reaches the liver. The...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Inhibitors Of Virion Release01:25

Inhibitors Of Virion Release

Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
Viral Hepatitis I: Introduction01:28

Viral Hepatitis I: Introduction

Viral hepatitis is an inflammatory condition of the liver caused by infection with hepatotropic viruses, most commonly hepatitis A, B, C, D, and E. Despite variations in structure and transmission, all viruses mentioned infect hepatocytes and provoke immune responses that can hinder liver function. Additionally, some non-hepatotropic viruses can also lead to hepatic inflammation.Hepatitis A VirusHepatitis A virus (HAV) is transmitted through the fecal–oral route, typically by ingestion of food...