Related Experiment Video

Updated: Jun 22, 2026

Rapid, Seamless Generation of Recombinant Poxviruses using Host Range and Visual Selection
09:25

Rapid, Seamless Generation of Recombinant Poxviruses using Host Range and Visual Selection

Published on: May 24, 2020

Ebola virus VP35 antagonizes PKR activity through its C-terminal interferon inhibitory domain

Michael Schümann1, Thorsten Gantke, Elke Mühlberger

  • 1Department of Virology, Philipps University Marburg, 35043 Marburg, Germany.

Journal of Virology
|June 12, 2009
PubMed

Insights

Ebola virus VP35 protein inhibits protein kinase R (PKR) activation and enhances protein synthesis. This antiviral mechanism is mediated by the same domain that inhibits interferon regulatory factor 3 (IRF3).

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Ebola virus VP35 protein has a C-terminal basic amino acid cluster crucial for double-stranded RNA (dsRNA) binding and inhibiting interferon regulatory factor 3 (IRF3).
  • VP35 also inhibits protein kinase R (PKR) activation, but the specific domain responsible for this function was previously undefined.

Purpose of the Study:

  • To identify the domain of Ebola virus VP35 responsible for inhibiting protein kinase R (PKR) activation.
  • To investigate the role of VP35 in enhancing protein synthesis and its relationship with PKR inhibition.

Main Methods:

  • Alanine substitution mutations were introduced into the basic amino acid cluster of Ebola virus VP35.
  • The effects of these mutations on dsRNA binding, IRF3 inhibition, PKR activation, and protein expression were analyzed.

Main Results:

  • The IRF3 inhibitory domain of VP35 was found to mediate PKR inhibition and enhance coexpressed protein synthesis.
  • Unlike dsRNA binding and IRF3 inhibition, abrogating PKR inhibition and enhanced protein expression required alanine substitutions in at least two basic amino acids.
  • Ebola virus infection was shown to not only block but also reverse PKR activation.

Conclusions:

  • The IRF3 inhibitory domain of Ebola virus VP35 plays a dual role in viral pathogenesis, inhibiting both IRF3 and PKR.
  • VP35-mediated PKR inhibition contributes to enhanced protein synthesis, a key viral strategy.
  • Ebola virus infection actively reverses PKR activation, suggesting a potent counter-innate immune response.

More Related Videos

Production of Pseudotyped Particles to Study Highly Pathogenic Coronaviruses in a Biosafety Level 2 Setting08:40

Production of Pseudotyped Particles to Study Highly Pathogenic Coronaviruses in a Biosafety Level 2 Setting

Published on: March 1, 2019

Modeling The Lifecycle Of Ebola Virus Under Biosafety Level 2 Conditions With Virus-like Particles Containing Tetracistronic Minigenomes10:11

Modeling The Lifecycle Of Ebola Virus Under Biosafety Level 2 Conditions With Virus-like Particles Containing Tetracistronic Minigenomes

Published on: September 27, 2014

Related Concept Videos

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...
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 Maturation and Assembly01:19

Inhibitors of Virion Maturation and Assembly

As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...
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...
Coronavirus01:29

Coronavirus

Coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV), are enveloped viruses characterized by their single-stranded, positive-sense RNA genome and helical nucleocapsid structure. The hallmark of these viruses is their club-shaped spike (S) glycoproteins that protrude from the viral envelope, facilitating attachment to host cells. Typically, coronaviruses infect the upper respiratory tract, often causing mild or asymptomatic disease. However, certain strains like...
Encephalitis ll: Pathophysiology01:26

Encephalitis ll: Pathophysiology

Encephalitis is inflammation of the brain parenchyma caused by direct viral invasion or immune-mediated mechanisms triggered by infections or tumors. Both processes lead to neuronal injury, disrupted neurotransmission, and diverse neurological symptoms, often with overlapping clinical and pathological features.Autoimmune EncephalitisIn autoimmune encephalitis, antibodies target neuronal antigens on cell surfaces, synapses, or within neurons. A key example is anti-NMDAR encephalitis, which can...