Related Experiment Video

Updated: Aug 22, 2025

Advanced Confocal Microscopy Techniques to Study Protein-protein Interactions and Kinetics at DNA Lesions
12:43

Advanced Confocal Microscopy Techniques to Study Protein-protein Interactions and Kinetics at DNA Lesions

Published on: November 12, 2017

11.0K

Effects of Caffeine, a DNA Damage Response Inhibitor, on Papillomavirus Genome Replication

Sriramana Kanginakudru1, Timra Gilson1, Leny Jose1

  • 1Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Pathogens (Basel, Switzerland)
|November 11, 2022
PubMed

Insights

Caffeine inhibits early human papillomavirus (HPV) replication by interfering with the DNA damage response (DDR). However, caffeine increases HPV DNA copy numbers during the viral genome maintenance stage.

Area of Science:

  • Virology
  • Molecular Biology
  • Cancer Research

Background:

  • Epidemiological studies link caffeinated coffee consumption to reduced oropharyngeal cancer risk.
  • Human papillomavirus (HPV) is a causative agent in oropharyngeal cancer.
  • Caffeine is known to inhibit the DNA damage response (DDR) pathway.

Purpose of the Study:

  • To investigate the effects of caffeine on the early replication stages of HPV31.
  • To determine if caffeine impacts viral entry and initial genome amplification.
  • To explore caffeine's influence on HPV genome maintenance replication.

Main Methods:

  • Utilized pseudo-virions (PsV) and quasi-virions (QsV) for HPV31 infection studies.
  • Assessed viral entry and HPV DNA copy number in caffeine-treated cells.
  • Performed transient transfection and stable cell line assays (CIN612E) with caffeine exposure.
  • Analyzed HPV31 E1 and E2 transcript levels and E2 protein binding to the viral origin of replication (ori).

Main Results:

  • Caffeine did not impede HPV31 viral entry.
  • Caffeine treatment led to a reduced HPV copy number in early infection stages.
  • Caffeine exposure increased HPV31 episome copy number in transfection and stable cell lines.
  • Increased steady-state levels of HPV31 E1 and E2 transcripts and enhanced E2 loading at the viral ori were observed with caffeine.

Conclusions:

  • Caffeine-mediated inhibition of the DDR pathway reduces early-stage HPV genome replication.
  • Inhibition of the DDR by caffeine may enhance viral amplicon replication during the HPV genome maintenance stage.
  • These findings suggest a differential effect of caffeine on HPV replication dynamics depending on the viral life cycle stage.
Keywords:
HPVcaffeinereplication

More Related Videos

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC Crosslinking of Small Molecules to Isolate Chromatin10:05

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC Crosslinking of Small Molecules to Isolate Chromatin

Published on: January 20, 2016

8.3K
Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling09:33

Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling

Published on: March 20, 2018

13.9K

Related Concept Videos

Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
5.2K
Viral Mutations00:36

Viral Mutations

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...
32.7K
S-Cdk Initiates DNA Replication02:38

S-Cdk Initiates DNA Replication

The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
4.8K
DNA Damage can Stall the Cell Cycle02:37

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...
9.3K
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
5.3K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.9K