Related Experiment Video
Updated: May 4, 2026
05:53
Use of In vivo Imaging to Monitor the Progression of Experimental Mouse Cytomegalovirus Infection in Neonates
Published on: July 6, 2013
14.3K
A novel DDB2-ATM feedback loop regulates human cytomegalovirus replication.
Xiaofei E1, George Savidis, Christopher R Chin
1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Journal of Virology
|December 17, 2013
Summary
Human cytomegalovirus (HCMV) replication depends on DNA damage binding protein 2 (DDB2), a nucleotide excision repair factor. DDB2 deficiency impairs viral gene expression and DNA replication, highlighting its crucial role in the HCMV life cycle.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Human cytomegalovirus (HCMV) genome replication is linked to host DNA damage responses (DDRs).
- DNA repair pathways may influence viral replication efficiency.
- Nucleotide excision repair (NER) is a key DNA repair pathway.
Purpose of the Study:
- To investigate the role of NER-associated factors in HCMV DNA replication.
- To determine the specific contribution of DNA damage binding protein 2 (DDB2) to HCMV replication.
- To elucidate the interplay between DDB2, viral gene expression, and replication compartments.
Main Methods:
- Utilized xeroderma pigmentosum (XP) complementation group E (XPE) fibroblasts with DDB2 mutations.
- Employed RNA interference (RNAi) to deplete DDB2 in normal fibroblasts.
- Assessed viral protein levels (IE2, pp65, gB55), viral DNA loads, and replication compartment formation.
- Investigated viral gene expression sensitivity to phosphonoacetic acid (PAA).
- Analyzed the interaction between DDB2 and ataxia telangiectasia mutated (ATM) during infection.
Main Results:
- XPE fibroblasts showed >2-log reduction in infectious progeny virus production.
- DDB2 depletion led to decreased expression of key HCMV proteins (IE2, pp65, gB55).
- Mature replication compartments were nearly absent in DDB2-deficient cells.
- Viral DNA loads were reduced by 1.5- to 2.0-logs in XPE cells.
- DDB2 deficiency affected viral gene expression similarly to PAA treatment, indicating an early role in replication.
- A novel DDB2-ATM feedback loop was identified during HCMV infection.
Conclusions:
- DNA damage binding protein 2 (DDB2) is essential for efficient HCMV DNA replication.
- DDB2 influences HCMV gene expression and the formation of replication compartments.
- A DDB2-ATM feedback loop plays a significant role in modulating HCMV replication.
Related Concept Videos
01:27Cytomegalovirus Disease
102
Cytomegalovirus (CMV) disease is caused by human cytomegalovirus, a double-stranded DNA virus of the Herpesviridae family. While primary CMV infection is often asymptomatic in immunocompetent individuals, the virus can cause severe disease in neonates and immunocompromised patients. CMV is the most common cause of congenital viral infection in the United States, and a major pathogen in solid organ and hematopoietic stem cell transplant recipients.CMV is transmitted via bodily fluids, sexual...
102
01:29Immune Response Against Viral Pathogens
2.4K
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...
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...
2.4K
00:36Viral Mutations
33.0K
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
33.0K
01:29Viruses with RNA Genomes
1.5K
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...
1.5K
02:36DNA Damage can Stall the Cell Cycle
8.5K
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...
8.5K