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Published in: Virology Journal 1/2015

Open Access 01-12-2015 | Research

DAXX modulates human papillomavirus early gene expression and genome replication in U2OS cells

Authors: Piia Kivipõld, Liisi Võsa, Mart Ustav, Reet Kurg

Published in: Virology Journal | Issue 1/2015

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Abstract

Background

The human papillomavirus (HPV) genomes can replicate, and are maintained as autonomously replicating extrachromosomal plasmids in human U2OS cells. Previous studies have shown that HPV genomes are transcriptionally active in U2OS cells and can express the viral early proteins required for initiation and establishment of HPV replication. In the present work, we have examined the involvement of cellular DAXX protein in HPV replication in U2OS cells.

Methods

We have used indirect immunofluorescence and FISH analysis in order to study HPV replication compartments in U2OS cells. In addition, we have used siRNA knock-down for examining the effect of the DAXX protein on HPV replication and transcription in U2OS cells.

Results

We show that a portion of HPV replication foci are partially co-localized with components of ND10, cellular DAXX and PML proteins. In addition, we demonstrate that the knock-down of the cellular DAXX protein modulates the HPV genome replication and transcription in U2OS cells – papillomavirus replication is reduced in the absence of this component of ND10.

Conclusions

The DAXX protein modulates the early gene expression and the transient replication of HPV genomes in U2OS cells.
Literature
1.
go back to reference Zur Hausen H. Papillomavirus infections--a major cause of human cancers. Biochim Biophys Acta. 1996;1288(2):F55–78.PubMed Zur Hausen H. Papillomavirus infections--a major cause of human cancers. Biochim Biophys Acta. 1996;1288(2):F55–78.PubMed
2.
go back to reference Kadaja M, Silla T, Ustav E, Ustav M. Papillomavirus DNA replication - from initiation to genomic instability. Virology. 2009;384(2):360–8.PubMedCrossRef Kadaja M, Silla T, Ustav E, Ustav M. Papillomavirus DNA replication - from initiation to genomic instability. Virology. 2009;384(2):360–8.PubMedCrossRef
3.
go back to reference Tavalai N, Stamminger T. New insights into the role of the subnuclear structure ND10 for viral infection. BBA. 1783;2008:2207–21. Tavalai N, Stamminger T. New insights into the role of the subnuclear structure ND10 for viral infection. BBA. 1783;2008:2207–21.
4.
go back to reference Swindle CS, Zou N, Van Tine BA, Shaw GM, Engler JA, Chow LT. Human papillomavirus DNA replication compartments in a transient DNA replication system. J Virol. 1999;73(2):1001–9.PubMedCentralPubMed Swindle CS, Zou N, Van Tine BA, Shaw GM, Engler JA, Chow LT. Human papillomavirus DNA replication compartments in a transient DNA replication system. J Virol. 1999;73(2):1001–9.PubMedCentralPubMed
5.
go back to reference Day PM, Baker CC, Lowy DR, Schiller JT. Establishment of papillomavirus infection is enhanced by promyelocytic leukemia protein (PML) expression. Proc Natl Acad Sci U S A. 2004;101(39):14252–7.PubMedCentralPubMedCrossRef Day PM, Baker CC, Lowy DR, Schiller JT. Establishment of papillomavirus infection is enhanced by promyelocytic leukemia protein (PML) expression. Proc Natl Acad Sci U S A. 2004;101(39):14252–7.PubMedCentralPubMedCrossRef
7.
go back to reference Stepp W, Meyers J, McBride A. Sp100 provides intrinsic immunity against human papillomavirus infection. mBio. 2013;4(6):e00845-00813.CrossRef Stepp W, Meyers J, McBride A. Sp100 provides intrinsic immunity against human papillomavirus infection. mBio. 2013;4(6):e00845-00813.CrossRef
8.
9.
go back to reference Ishov A, Sotnikov A, Negorev D, Vladimirova O, Neff N, Kamitani T, et al. PML is critical for ND10 formation and recruits the PML-interacting protein daxx to this nuclear structure when modified by SUMO-1. J Cell Biol. 1999;147(2):221–34.PubMedCentralPubMedCrossRef Ishov A, Sotnikov A, Negorev D, Vladimirova O, Neff N, Kamitani T, et al. PML is critical for ND10 formation and recruits the PML-interacting protein daxx to this nuclear structure when modified by SUMO-1. J Cell Biol. 1999;147(2):221–34.PubMedCentralPubMedCrossRef
10.
go back to reference Hollenbach A, McPherson C, Mientjes E, Iyengar R, Grosveld G. Daxx and histone deacetylase II associate with chromatin through an interaction with core histones and the chromatin-associated protein Dek. J Cell Sci. 2002;115:3319–30.PubMed Hollenbach A, McPherson C, Mientjes E, Iyengar R, Grosveld G. Daxx and histone deacetylase II associate with chromatin through an interaction with core histones and the chromatin-associated protein Dek. J Cell Sci. 2002;115:3319–30.PubMed
11.
go back to reference Li H, Leo C, Zhu J, Wu X, O'Neil J, Park E, et al. Sequestration and inhibition of Daxx-mediated transcriptional repression by PML. Mol Cell Biol. 2000;5:1784–96.CrossRef Li H, Leo C, Zhu J, Wu X, O'Neil J, Park E, et al. Sequestration and inhibition of Daxx-mediated transcriptional repression by PML. Mol Cell Biol. 2000;5:1784–96.CrossRef
12.
13.
go back to reference Poleshko A, Palagin I, Zhang R, Boimel P, Castagna C, Adams P, et al. Identification of cellular proteins that maintain retroviral epigenetic silencing: evidence for an antiviral response. J Virol. 2008;82(5):2313–23.PubMedCentralPubMedCrossRef Poleshko A, Palagin I, Zhang R, Boimel P, Castagna C, Adams P, et al. Identification of cellular proteins that maintain retroviral epigenetic silencing: evidence for an antiviral response. J Virol. 2008;82(5):2313–23.PubMedCentralPubMedCrossRef
14.
go back to reference Saffert R, Kalejta R. Human cytomegalovirus gene expression is silenced by Daxx-mediated intrinsic immune defense in model latent infections established in vitro. J Virol. 2007;81(17):9109–20.PubMedCentralPubMedCrossRef Saffert R, Kalejta R. Human cytomegalovirus gene expression is silenced by Daxx-mediated intrinsic immune defense in model latent infections established in vitro. J Virol. 2007;81(17):9109–20.PubMedCentralPubMedCrossRef
15.
go back to reference Woodhall D, Groves I, Reeves M, Wilkinson G, Sinclair J. Human Daxx-mediated repression of human cytomegalovirus gene expression correlates with a repressive chromatin structure around the major immediate early promoter. J Biol Chem. 2006;281(49):37652–60.PubMedCrossRef Woodhall D, Groves I, Reeves M, Wilkinson G, Sinclair J. Human Daxx-mediated repression of human cytomegalovirus gene expression correlates with a repressive chromatin structure around the major immediate early promoter. J Biol Chem. 2006;281(49):37652–60.PubMedCrossRef
16.
go back to reference Schreiner S, Wimmer P, Sirma H, Everett R, Blanchette P, Groitl P, et al. Proteasome-dependent degradation of Daxx by the viral E1B-55 K protein in human adenovirus-infected cells. J Virol. 2010;84(14):7029–38.PubMedCentralPubMedCrossRef Schreiner S, Wimmer P, Sirma H, Everett R, Blanchette P, Groitl P, et al. Proteasome-dependent degradation of Daxx by the viral E1B-55 K protein in human adenovirus-infected cells. J Virol. 2010;84(14):7029–38.PubMedCentralPubMedCrossRef
17.
go back to reference Shalginskikh N, Poleshko A, Skalka A, Katz R. Retroviral DNA methylation and epigenetic repression are mediated by the antiviral host protein Daxx. J Virol. 2013;87(4):2137–50.PubMedCentralPubMedCrossRef Shalginskikh N, Poleshko A, Skalka A, Katz R. Retroviral DNA methylation and epigenetic repression are mediated by the antiviral host protein Daxx. J Virol. 2013;87(4):2137–50.PubMedCentralPubMedCrossRef
18.
go back to reference Greger J, Katz R, Ishov A, Maul G, Skalka A. The cellular protein daxx interacts with avian sarcoma virus integrase and viral DNA to repress viral transcription. J Virol. 2005;79(8):4610–8.PubMedCentralPubMedCrossRef Greger J, Katz R, Ishov A, Maul G, Skalka A. The cellular protein daxx interacts with avian sarcoma virus integrase and viral DNA to repress viral transcription. J Virol. 2005;79(8):4610–8.PubMedCentralPubMedCrossRef
19.
go back to reference Geimanen J, Isok-Paas H, Pipitch R, Salk K, Laos T, Orav M, et al. Development of a cellular assay system to study the genome replication of high- and low-risk mucosal and cutaneous human papillomaviruses. J Virol. 2011;85(7):3315–29.PubMedCentralPubMedCrossRef Geimanen J, Isok-Paas H, Pipitch R, Salk K, Laos T, Orav M, et al. Development of a cellular assay system to study the genome replication of high- and low-risk mucosal and cutaneous human papillomaviruses. J Virol. 2011;85(7):3315–29.PubMedCentralPubMedCrossRef
20.
go back to reference Ustav M, Stenlund A. Transient replication of BPV-1 requires two viral polypeptides encoded by the E1 and E2 open reading frames. EMBO J. 1991;10(2):449–57.PubMedCentralPubMed Ustav M, Stenlund A. Transient replication of BPV-1 requires two viral polypeptides encoded by the E1 and E2 open reading frames. EMBO J. 1991;10(2):449–57.PubMedCentralPubMed
21.
go back to reference Sakakibara N, Chen D, Jang M, Kang D, Luecke H, Wu S, et al. Brd4 is displaced from HPV replication factories as they expand and amplify viral DNA. PLoS Pathog. 2013;9(11), e1003777.PubMedCentralPubMedCrossRef Sakakibara N, Chen D, Jang M, Kang D, Luecke H, Wu S, et al. Brd4 is displaced from HPV replication factories as they expand and amplify viral DNA. PLoS Pathog. 2013;9(11), e1003777.PubMedCentralPubMedCrossRef
22.
go back to reference Day P, Roden R, Lowy D, Schiller J. The papillomavirus minor capsid protein, L2, induces localization of the major capsid protein, L1, and the viral transcription/replication protein, E2, to PML oncogenic domains. J Virol. 1998;72(1):142–50.PubMedCentralPubMed Day P, Roden R, Lowy D, Schiller J. The papillomavirus minor capsid protein, L2, induces localization of the major capsid protein, L1, and the viral transcription/replication protein, E2, to PML oncogenic domains. J Virol. 1998;72(1):142–50.PubMedCentralPubMed
23.
go back to reference Heino P, Zhou J, Lambert P. Interaction of the papillomavirus transcription/replication factor, E2, and the viral capsid protein, L2. Virology. 2000;276(2):304–14.PubMedCrossRef Heino P, Zhou J, Lambert P. Interaction of the papillomavirus transcription/replication factor, E2, and the viral capsid protein, L2. Virology. 2000;276(2):304–14.PubMedCrossRef
24.
go back to reference Kurg R, Uusen P, Vosa L, Ustav M. Human papillomavirus E2 protein with single activation domain initiates HPV18 genome replication, but is not sufficient for long-term maintenance of virus genome. Virology. 2010;408(2):159–66.PubMedCrossRef Kurg R, Uusen P, Vosa L, Ustav M. Human papillomavirus E2 protein with single activation domain initiates HPV18 genome replication, but is not sufficient for long-term maintenance of virus genome. Virology. 2010;408(2):159–66.PubMedCrossRef
25.
go back to reference Reinson T, Toots M, Kadaja M, Pipitch R, Allik M, Ustav E, et al. Engagement of the ATR-dependent DNA damage response at the human papillomavirus 18 replication centers during the initial amplification. J Virol. 2013;87(2):951–64.PubMedCentralPubMedCrossRef Reinson T, Toots M, Kadaja M, Pipitch R, Allik M, Ustav E, et al. Engagement of the ATR-dependent DNA damage response at the human papillomavirus 18 replication centers during the initial amplification. J Virol. 2013;87(2):951–64.PubMedCentralPubMedCrossRef
26.
go back to reference Toots M, Männik A, Kivi G, Ustav MJ, Ustav E, Ustav M. The transcription map of human papillomavirus type 18 during genome replication in U2OS cells. PLoS One. 2014;9(12), e116151.PubMedCentralPubMedCrossRef Toots M, Männik A, Kivi G, Ustav MJ, Ustav E, Ustav M. The transcription map of human papillomavirus type 18 during genome replication in U2OS cells. PLoS One. 2014;9(12), e116151.PubMedCentralPubMedCrossRef
27.
go back to reference Rivera-Molina Y, Rojas B, Tang Q. Nuclear domain 10-associated proteins recognize and segregate intranuclear DNA/protein complexes to negate gene expression. Virol J. 2012;9:222.PubMedCentralPubMedCrossRef Rivera-Molina Y, Rojas B, Tang Q. Nuclear domain 10-associated proteins recognize and segregate intranuclear DNA/protein complexes to negate gene expression. Virol J. 2012;9:222.PubMedCentralPubMedCrossRef
28.
go back to reference Ishov A, Maul G. The periphery of nuclear domain 10 (ND10) as site of DNA virus deposition. J Cell Biol. 1996;134(4):815–26.PubMedCrossRef Ishov A, Maul G. The periphery of nuclear domain 10 (ND10) as site of DNA virus deposition. J Cell Biol. 1996;134(4):815–26.PubMedCrossRef
30.
go back to reference Kadaja M, Isok-Paas H, Laos T, Ustav E, Ustav M. Mechanism of genomic instability in cells infected with the high-risk human papillomaviruses. PLoS Pathog. 2009;5(4), e1000397.PubMedCentralPubMedCrossRef Kadaja M, Isok-Paas H, Laos T, Ustav E, Ustav M. Mechanism of genomic instability in cells infected with the high-risk human papillomaviruses. PLoS Pathog. 2009;5(4), e1000397.PubMedCentralPubMedCrossRef
31.
go back to reference Moody C, Laimins L. Human papillomaviruses activate the ATM DNA damage pathway for viral genome amplification upon differentiation. PLoS Pathog. 2009;5(10), e1000605.PubMedCentralPubMedCrossRef Moody C, Laimins L. Human papillomaviruses activate the ATM DNA damage pathway for viral genome amplification upon differentiation. PLoS Pathog. 2009;5(10), e1000605.PubMedCentralPubMedCrossRef
32.
go back to reference Sakakibara N, Mitra R, McBride A. The papillomavirus E1 helicase activates a cellular DNA damage response in viral replication foci. J Virol. 2011;85(17):8981–95.PubMedCentralPubMedCrossRef Sakakibara N, Mitra R, McBride A. The papillomavirus E1 helicase activates a cellular DNA damage response in viral replication foci. J Virol. 2011;85(17):8981–95.PubMedCentralPubMedCrossRef
33.
go back to reference Anacker D, Gautam D, Gillespie K, Chappell W, Moody C. Productive replication of human papillomavirus 31 requires DNA repair factor Nbs1. J Virol. 2014;15:8528–44.CrossRef Anacker D, Gautam D, Gillespie K, Chappell W, Moody C. Productive replication of human papillomavirus 31 requires DNA repair factor Nbs1. J Virol. 2014;15:8528–44.CrossRef
34.
go back to reference Everett R. Interactions between DNA viruses, ND10 and the DNA damage response. Cell Microbiol. 2006;8(3):365–74.PubMedCrossRef Everett R. Interactions between DNA viruses, ND10 and the DNA damage response. Cell Microbiol. 2006;8(3):365–74.PubMedCrossRef
35.
go back to reference Dellaire G, Ching R, Ahmed K, Jalali F, Tse K, Bristow R, et al. Promyelocytic leukemia nuclear bodies behave as DNA damage sensors whose response to DNA double-strand breaks is regulated by NBS1 and the kinases ATM, Chk2, and ATR. J Cell Biol. 2006;175(1):55–66.PubMedCentralPubMedCrossRef Dellaire G, Ching R, Ahmed K, Jalali F, Tse K, Bristow R, et al. Promyelocytic leukemia nuclear bodies behave as DNA damage sensors whose response to DNA double-strand breaks is regulated by NBS1 and the kinases ATM, Chk2, and ATR. J Cell Biol. 2006;175(1):55–66.PubMedCentralPubMedCrossRef
36.
go back to reference Chiang C, Ustav M, Stenlund A, Ho T, Broker T, Chow L. Viral E1 and E2 proteins support replication of homologous and heterologous papillomaviral origins. Proc Natl Acad Sci U S A. 1992;89(13):5799–803.PubMedCentralPubMedCrossRef Chiang C, Ustav M, Stenlund A, Ho T, Broker T, Chow L. Viral E1 and E2 proteins support replication of homologous and heterologous papillomaviral origins. Proc Natl Acad Sci U S A. 1992;89(13):5799–803.PubMedCentralPubMedCrossRef
38.
go back to reference Ustav M, Ustav E, Szymanski P, Stenlund A. Identification of the origin of replication of bovine papillomavirus and characterization of the viral origin recognition factor E1. EMBO J. 1991;10(13):4321–9.PubMedCentralPubMed Ustav M, Ustav E, Szymanski P, Stenlund A. Identification of the origin of replication of bovine papillomavirus and characterization of the viral origin recognition factor E1. EMBO J. 1991;10(13):4321–9.PubMedCentralPubMed
39.
go back to reference Orav M, Henno L, Isok-Paas H, Geimanen J, Ustav M, Ustav E. Recombination-dependent oligomerization of human papillomavirus genomes upon transient DNA replication. J Virol. 2013;87(22):12051–68.PubMedCentralPubMedCrossRef Orav M, Henno L, Isok-Paas H, Geimanen J, Ustav M, Ustav E. Recombination-dependent oligomerization of human papillomavirus genomes upon transient DNA replication. J Virol. 2013;87(22):12051–68.PubMedCentralPubMedCrossRef
40.
go back to reference Ilves I, Maemets K, Silla T, Janikson K, Ustav M. Brd4 is involved in multiple processes of the bovine papillomavirus type 1 life cycle. J Virol. 2006;80(7):3660–5.PubMedCentralPubMedCrossRef Ilves I, Maemets K, Silla T, Janikson K, Ustav M. Brd4 is involved in multiple processes of the bovine papillomavirus type 1 life cycle. J Virol. 2006;80(7):3660–5.PubMedCentralPubMedCrossRef
Metadata
Title
DAXX modulates human papillomavirus early gene expression and genome replication in U2OS cells
Authors
Piia Kivipõld
Liisi Võsa
Mart Ustav
Reet Kurg
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2015
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-015-0335-z

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