Related Experiment Video
Updated: Jun 26, 2026
09:25
Rapid, Seamless Generation of Recombinant Poxviruses using Host Range and Visual Selection
Published on: May 24, 2020
Orthopoxviruses require a functional ubiquitin-proteasome system for productive replication
Alastair Teale1, Stephanie Campbell, Nick Van Buuren
1Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
Journal of Virology
|December 26, 2008
Summary
Poxvirus infection requires a functional ubiquitin-proteasome system for viral replication and propagation. Inhibiting this system blocks viral factories and late gene expression, but early gene expression continues.
Area of Science:
- Virology
- Molecular Biology
- Cellular Biology
Background:
- Cellular homeostasis relies on protein balance, with the ubiquitin-proteasome pathway crucial for protein degradation.
- Poxviruses utilize the ubiquitin-proteasome system, encoding proteins that interact with cellular ubiquitin ligases.
- Proteasome inhibitors are known to block protein degradation.
Purpose of the Study:
- To investigate the impact of proteasome inhibitors on poxvirus infection.
- To determine the role of the ubiquitin-proteasome system in poxvirus replication and propagation.
Main Methods:
- Treatment of poxvirus-infected cells with various proteasome inhibitors (MG132, MG115, lactacystin, bortezomib).
- Confocal microscopy to visualize viral replication factories.
- Assessment of viral gene expression (early and late) and DNA replication.
- Measurement of viral titers.
- Use of an ubiquitin-activating enzyme (E1) inhibitor.
Main Results:
- Proteasome inhibitors MG132 and bortezomib significantly blocked poxvirus infection, preventing viral replication factories, late gene expression, and DNA replication.
- Early gene expression remained unaffected by these inhibitors.
- Viral titers were severely reduced by proteasomal inhibition.
- Inhibition effects were reversible upon removal of MG132.
- An E1 inhibitor also impacted late and early protein expression.
Conclusions:
- A functional ubiquitin-proteasome system is essential for efficient poxvirus infection.
- Targeting the ubiquitin-proteasome pathway offers a potential strategy to inhibit poxvirus replication.
Related Concept Videos
01:20Viral Replication: Lytic Cycle
Bacteriophages, or phages, are viruses that specifically infect bacteria. Among them, T-even bacteriophages, such as T4, exhibit a well-characterized lytic replication cycle in Escherichia coli (E. coli). This process ensures the rapid proliferation of the virus while ultimately leading to the destruction of the bacterial host.Attachment and DNA InjectionThe infection process begins with the recognition and binding of the T4 phage to the E. coli cell surface. Tail fibers of the phage...
01:29Viruses 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...
01:19Inhibitors 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...
01:30Inhibitors 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...
01:10Retrovirus Life Cycles
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the retrovirus to...
01:16Viral Replication: Lysogenic Cycle
The lysogenic cycle is a crucial viral replication strategy that allows bacteriophages to persist within host cells without immediately destroying them. This process is primarily observed in temperate phages, such as bacteriophage lambda (λ), which infects Escherichia coli. The cycle allows the viral genome to persist across bacterial generations while keeping host cells viable.Integration of the Viral GenomeUpon infection, bacteriophage lambda attaches to the bacterial surface and injects its...