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PARP1 Stabilizes CTCF Binding and Chromatin Structure To Maintain Epstein-Barr Virus Latency Type

Overview of attention for article published in Journal of Virology, August 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (86th percentile)
  • High Attention Score compared to outputs of the same age and source (90th percentile)

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Title
PARP1 Stabilizes CTCF Binding and Chromatin Structure To Maintain Epstein-Barr Virus Latency Type
Published in
Journal of Virology, August 2018
DOI 10.1128/jvi.00755-18
Pubmed ID
Authors

Lena N. Lupey-Green, Lisa B. Caruso, Jozef Madzo, Kayla A. Martin, Yinfei Tan, Michael Hulse, Italo Tempera

Abstract

Epstein Barr Virus (EBV) is a potentially oncogenic gammaherpesvirus that establishes a chronic, latent infection in memory B cells. The EBV genome persists in infected host cells as a chromatinized episome and is subject to chromatin-mediated regulation. Binding of the host insulator protein CTCF to the EBV genome has an established role in maintaining viral latency type. CTCF is post-translationally modified by the host enzyme PARP1. PARP1, or Poly(ADP-ribose) polymerase 1, catalyzes the transfer of a poly(ADP-ribose) (PAR) moiety from NAD+ onto acceptor proteins including itself, histone proteins, and CTCF. PARylation of CTCF by PARP1 can affect CTCF's insulator activity, DNA binding capacity, and ability to form chromatin loops. Both PARP1 and CTCF have been implicated in the regulation of EBV latency and lytic reactivation. Thus, we predicted that pharmacological inhibition with PARP1 inhibitors would affect EBV latency type through a chromatin-specific mechanism. Here, we show that PARP1 and CTCF colocalize at specific sites throughout the EBV genome, and provide evidence to suggest that PARP1 acts to stabilize CTCF binding and maintain the open chromatin landscape at the active Cp promoter during type III latency. Further, PARP1 activity is important in maintaining latency type-specific viral gene expression. The data presented here provide a rationale for the use of PARP inhibitors in the treatment of EBV-associated cancers exhibiting type III latency, and could ultimately contribute to an EBV-specific treatment strategy for AIDS-related or post-transplant lymphomas.IMPORTANCE Epstein Barr Virus (EBV) is a human gammaherpesvirus that infects more than 95% of individuals worldwide. Upon infection, EBV circularizes as an episome, and establishes a chronic, latent infection in B cells. In doing so, the virus utilizes host cell machinery to regulate and maintain the viral genome. In otherwise healthy individuals, EBV infection is typically non-pathological; however, latent infection is potentially oncogenic, and is responsible for 1% of human cancers. During latent infection, EBV expresses specific sets of proteins according to the given latency type, each of which is associated with specific types of cancers. For example, type III latency, in which the virus expresses its full repertoire of latent proteins, is characteristic of AIDS-associated and post-transplant lymphomas associated with EBV infection. Understanding how viral latency type is regulated at the chromatin level may reveal potential targets for EBV-specific pharmacological intervention in EBV-associated cancers.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 48 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 48 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 12 25%
Researcher 11 23%
Student > Bachelor 5 10%
Student > Master 4 8%
Professor 1 2%
Other 2 4%
Unknown 13 27%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 16 33%
Medicine and Dentistry 6 13%
Agricultural and Biological Sciences 5 10%
Chemistry 2 4%
Immunology and Microbiology 2 4%
Other 3 6%
Unknown 14 29%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 15. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 February 2022.
All research outputs
#2,369,377
of 25,385,509 outputs
Outputs from Journal of Virology
#1,373
of 25,700 outputs
Outputs of similar age
#47,132
of 344,555 outputs
Outputs of similar age from Journal of Virology
#20
of 211 outputs
Altmetric has tracked 25,385,509 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 25,700 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.5. This one has done particularly well, scoring higher than 94% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 344,555 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 86% of its contemporaries.
We're also able to compare this research output to 211 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 90% of its contemporaries.