Related Experiment Video

Updated: May 29, 2026

Quantification of γH2AX Foci in Response to Ionising Radiation
06:53

Quantification of γH2AX Foci in Response to Ionising Radiation

Published on: April 6, 2010

Gammaherpesvirus gene expression and DNA synthesis are facilitated by viral protein kinase and histone variant H2AX

Bryan C Mounce1, Fei Chin Tsan, Lindsay Droit

  • 1Department of Microbiology and Molecular Genetics, Cancer Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA.

Virology
|September 28, 2011
PubMed

Insights

Mouse gammaherpesvirus-68 protein kinase orf36 exploits the DNA damage response (DDR) system, specifically H2AX, to enhance viral gene expression and DNA replication in macrophages. This highlights a novel therapeutic target for gammaherpesvirus infections.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Gammaherpesvirus protein kinases are crucial for viral replication and latency.
  • Their precise mechanisms, especially in primary cells, remain largely unknown.
  • Understanding these kinases is vital for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of mouse gammaherpesvirus-68 (MHV68) protein kinase orf36 in primary macrophages.
  • To elucidate the involvement of the DNA damage response (DDR) pathway, particularly H2AX, in MHV68 replication.
  • To explore the implications for gammaherpesvirus pathogenesis.

Main Methods:

  • Infection of primary macrophages with MHV68.
  • Analysis of viral gene expression (RTA) and DNA synthesis.
  • Assessment of H2AX phosphorylation and its association with viral promoters.
  • Comparison of replication in H2AX-deficient versus wild-type macrophages.

Main Results:

  • orf36 facilitated RTA gene expression and viral DNA synthesis in primary macrophages.
  • H2AX expression supported efficient RTA transcription.
  • Phosphorylated H2AX was found associated with the RTA promoter.
  • MHV68 replication was significantly reduced in H2AX-deficient macrophages.

Conclusions:

  • MHV68 protein kinase orf36 utilizes the host DDR system, including H2AX, to promote viral replication.
  • H2AX plays a critical role in regulating viral gene expression and DNA synthesis.
  • The findings suggest gammaherpesviruses exploit host tumor suppressor pathways, impacting pathogenesis.

More Related Videos

Purification of Viral DNA for the Identification of Associated Viral and Cellular Proteins08:26

Purification of Viral DNA for the Identification of Associated Viral and Cellular Proteins

Published on: August 31, 2017

Functional Imaging of Viral Transcription Factories Using 3D Fluorescence Microscopy09:03

Functional Imaging of Viral Transcription Factories Using 3D Fluorescence Microscopy

Published on: January 18, 2018

Related Concept Videos

Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
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...
Size and Structure of Viral Genomes01:26

Size and Structure of Viral Genomes

Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
Herpes01:28

Herpes

Herpes simplex type 1 (HSV‑1) is a widespread pathogen responsible for orolabial lesions. It is an enveloped, double-stranded DNA (dsDNA) virus belonging to the family Herpesviridae. Once the virus infects a host cell, its double‑stranded DNA genome is delivered into the nucleus, where a coordinated cascade of immediate‑early, early, and late gene expression directs viral DNA replication, structural protein synthesis, and virion assembly. After primary infection of epithelial cells, HSV-1...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...