Merkel Cell Polyomavirus DNA Replication Induces Senescence in Human Dermal Fibroblasts in a Kap1/Trim28-Dependent Manner.

MBio
Svenja SiebelsNicole Fischer

Abstract

Merkel cell polyomavirus (MCPyV) is the only polyomavirus known to be associated with tumorigenesis in humans. Similarly to other polyomaviruses, MCPyV expresses a large tumor antigen (LT-Ag) that, together with a small tumor antigen (sT-Ag), contributes to cellular transformation and that is of critical importance for the initiation of the viral DNA replication. Understanding the cellular protein network regulated by MCPyV early proteins will significantly contribute to our understanding of the natural MCPyV life cycle as well as of the mechanisms by which the virus contributes to cellular transformation. We here describe KRAB-associated protein 1 (Kap1), a chromatin remodeling factor involved in cotranscriptional regulation, as a novel protein interaction partner of MCPyV T antigens sT and LT. Kap1 knockout results in a significant increase in the level of viral DNA replication that is highly suggestive of Kap1 being an important host restriction factor during MCPyV infection. Differently from other DNA viruses, MCPyV gene expression is unaffected in the absence of Kap1 and Kap1 does not associate with the viral genome. Instead, we show that in primary normal human dermal fibroblast (nHDF) cells, MCPyV DNA replication, but no...Continue Reading

References

Jul 1, 1977·The Journal of General Virology·F L GrahamR Nairn
Jul 20, 2007·Methods in Molecular Biology·Koji ItahanaGoberdhan P Dimri
Jan 19, 2008·Science·Huichen FengPatrick S Moore
Sep 19, 2008·Genome Biology·Yong ZhangX Shirley Liu
Sep 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·Masahiro ShudaYuan Chang
Mar 6, 2009·Genome Biology·Ben LangmeadSteven L Salzberg
Sep 4, 2009·Current Protocols in Bioinformatics·Da Wei HuangRichard A Lempicki
Sep 5, 2009·Nature Protocols·Michael H TathamRonald T Hay
Jan 16, 2010·Nature·Helen M RoweDidier Trono
Jun 15, 2010·Cell Host & Microbe·Rachel M SchowalterChristopher B Buck
Feb 24, 2011·Molecular and Cellular Biology·Sushma IyengarPeggy J Farnham
Jun 10, 2011·The Journal of Biological Chemistry·Sushma Iyengar, Peggy J Farnham
Jun 15, 2011·Cell Host & Microbe·Awatef AllouchAnna Cereseto
Jul 30, 2011·PloS One·Huichen FengPatrick S Moore
Jun 20, 2012·Current Opinion in Virology·Reety AroraPatrick S Moore
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Jan 9, 2013·Methods in Molecular Biology·Francis Rodier
Mar 22, 2013·Journal of Virology·Jingwei ChengJames A DeCaprio
Aug 28, 2014·Immunology Letters·Joana Santos, Jesús Gil
Sep 17, 2014·World Journal of Biological Chemistry·Chun-Ting ChengDavid K Ann
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Feb 15, 2015·Current Opinion in Virology·Justin A WendzickiYuan Chang
May 8, 2015·Journal of Virology·Gretchen L BentzJoseph S Pagano
Aug 4, 2015·Current Protocols in Microbiology·Friederike NeumannNicole Fischer
Oct 9, 2015·Current Opinion in Virology·Adam Grundhoff, Nicole Fischer
Nov 6, 2015·Journal of Virology·Carolin BürckSabrina Schreiner
Jan 9, 2016·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Paul W HarmsSteven D Billings
Feb 9, 2016·Current Protocols in Microbiology·Thomas GüntherAdam Grundhoff
Mar 2, 2016·Nature Structural & Molecular Biology·Mads LerdrupKlaus Hansen

❮ Previous
Next ❯

Citations

Jul 28, 2020·Cells·Daniel HumphreysTeresa Frisan
Nov 25, 2020·Annual Review of Pathology·James A DeCaprio
Dec 16, 2020·Biology·Rocío SeoaneCarmen Rivas

❮ Previous
Next ❯

Datasets Mentioned

BETA
PRJEB30502

Methods Mentioned

BETA
coimmunoprecipitation
Co-IPs
pulldown
Co-IP
PCR
transfection
ChIP
ChIP-seq
electrophoretic mobility shift
Electrophoretic mobility shift assay

Software Mentioned

SASP
SPSS
Fiji
MACS
DAVID
Star
FlowJo
Ingenuity pathway analysis IPA
ImageJ
DeSeq2

Related Concepts

Related Feeds

BK Virus Infection

BK virus infection is a significant complication of modern immunosuppression used in kidney transplantation. Discover the latest research on BK virus infection here.

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.