Evidence map›Paper›PMID 21901143›Full record

ArticlePloS one2011

Upregulation of cellular Bcl-2 by the KSHV encoded RTA promotes virion production.

Jianming Gao, Qiliang Cai, Jie Lu, Hem Chandra Jha, Erle S Robertson

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.0field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

Jianming GaoDepartment of Microbiology and the Tumor Virology Program of the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Qiliang Cai
Jie Lu
Hem Chandra Jha
Erle S Robertson
University of Pennsylvania · USChina Three Gorges University · CN

Funding

Mechanisms of Action of LANA encoded by KSHVR01CA091792 · NCI · UNIVERSITY OF PENNSYLVANIA · PI ROBERTSON, ERLE S. · 2002 to 2011
$3.4M
Mechanism of EBNA mediated cell migrationR01CA108461 · NCI · UNIVERSITY OF PENNSYLVANIA · PI ROBERTSON, ERLE S. · 2004 to 2008
$1.7M
KSHV Latency control by RtaR01AI067037 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ROBERTSON, ERLE S. · 2006 to 2010
$1.6M
EBV Antigen and Cell Cycle RegulationR01CA137894 · NCI · UNIVERSITY OF PENNSYLVANIA · PI ROBERTSON, ERLE S. · 2009 to 2013
$1.4M
Mechanism of KSHV reactivationR01DE017338 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI ROBERTSON, ERLE S · 2005 to 2007
$811k
EBNA3C and tumor supressorsR01CA138434 · NCI · UNIVERSITY OF PENNSYLVANIA · PI ROBERTSON, ERLE S. · 2009 to 2010
$637k
NCI NIH HHS 1R01CA137894-01NCI NIH HHS 1R01CA138434-01A209NCI NIH HHS 5R01CA091792-08NCI NIH HHS 5R01CA108461-05NCI NIH HHS R01 CA091792NCI NIH HHS R01 CA108461NCI NIH HHS R01 CA137894NCI NIH HHS R01 CA138434NIAID NIH HHS 5R01AI067037-04NIAID NIH HHS R01 AI067037NIDCR NIH HHS 5R01DE017338-03NIDCR NIH HHS R01 DE017338
6 · The paper itself

Abstract

Apoptosis of virus infected cells can restrict or dampen full blown virus propagation and this can serve as a protective mechanism against virus infection. Consequently, viruses can also delay programmed cell death by enhancing the expression of anti-apoptotic proteins. Human Bcl-2 is expressed on the surface of the mitochondrial membrane and functions as the regulator of the delicate balance between cell survival and apoptosis. In this report, we showed that the replication and transcription activator (RTA) encoded by KSHV ORF 50, a key regulator for KSHV reactivation from latent to lytic infection, upregulates the mRNA and protein levels of Bcl-2 in 293 cells, and TPA-induced KSHV-infected cells. Further analysis revealed that upregulation of the cellular Bcl-2 promoter by RTA is dose-dependent and acts through targeting of the CCN(9)GG motifs within the Bcl-2 promoter. The Bcl-2 P2 but not the P1 promoter is primarily responsive to RTA. The results of ChIP confirmed the direct interaction of RTA protein with the CCN(9)GG motifs. Knockdown of cellular Bcl-2 by lentivirus-delivered small hairpin RNA (shRNA) resulted in increased cell apoptosis and decreased virion production in KSHV-infected cells. These findings provide an insight into another mechanism by which KSHV utilizes the intrinsic apoptosis signaling pathways for prolonging the survival of lytically infected host cells to allow for maximum production of virus progeny.

Indexed as

ApoptosisBlotting, NorthernBlotting, WesternCell LineChromatin ImmunoprecipitationHerpesvirus 8, HumanHumansImmediate-Early ProteinsPolymerase Chain ReactionProto-Oncogene Proteins c-bcl-2Real-Time Polymerase Chain ReactionRNA InterferenceTrans-ActivatorsVirionImmediate-Early ProteinsProto-Oncogene Proteins c-bcl-2Rta protein, Human herpesvirus 8Trans-Activators

Identifiers

PMID21901143
PMCPMC3162012
OpenAlexW1992945755

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.