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

Virology Journal

Reet Kurg¹  Mart Ustav¹  Liisi Võsa¹  Piia Kivipõld¹ 

[1] Institute of Technology, University of Tartu, Nooruse 1, Tartu, 50411, Estonia

关键词: DAXX;    Virus-host interaction;    Replication;    Transcription;    Papillomavirus;   

Others  :  1224905
DOI  :  10.1186/s12985-015-0335-z

 received in 2015-05-04, accepted in 2015-06-30,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Kivipõld et al.

【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Fig. 5.

【 参考文献 】

• [1]Zur Hausen H. Papillomavirus infections--a major cause of human cancers. Biochim Biophys Acta. 1996; 1288(2):F55-78.
• [2]Kadaja M, Silla T, Ustav E, Ustav M. Papillomavirus DNA replication - from initiation to genomic instability. Virology. 2009; 384(2):360-368.
• [3]Tavalai N, Stamminger T. New insights into the role of the subnuclear structure ND10 for viral infection. BBA. 1783; 2008:2207-2221.
• [4]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):1001-1009.
• [5]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):14252-14257.
• [6]Nakahara T, Lambert P. Induction of promyelocytic leukemia (PML) oncogenic domains (PODs) by papillomavirus. Virology. 2007; 366(2):316-329.
• [7]Stepp W, Meyers J, McBride A. Sp100 provides intrinsic immunity against human papillomavirus infection. mBio. 2013; 4(6):e00845-00813.
• [8]Salomoni P, Khelifi A. Daxx: death or survival protein? Trends Cell Biol. 2006; 16:97-104.
• [9]Ishov A, Sotnikov A, Negorev D, Vladimirova O, Neff N, Kamitani T, Yeh E, Strauss J, Maul G. 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):221-234.
• [10]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; 115:3319-3330.
• [11]Li H, Leo C, Zhu J, Wu X, O'Neil J, Park E, Chen J. Sequestration and inhibition of Daxx-mediated transcriptional repression by PML. Mol Cell Biol. 2000; 5:1784-1796.
• [12]Puto L, Reed J. Daxx represses RelB target promoters via DNA methyltransferase recruitment and DNA hypermethylation. Genes Dev. 2008; 22:998-1010.
• [13]Poleshko A, Palagin I, Zhang R, Boimel P, Castagna C, Adams P, Skalka A, Katz R. Identification of cellular proteins that maintain retroviral epigenetic silencing: evidence for an antiviral response. J Virol. 2008; 82(5):2313-2323.
• [14]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):9109-9120.
• [15]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):37652-37660.
• [16]Schreiner S, Wimmer P, Sirma H, Everett R, Blanchette P, Groitl P, Dobner T. Proteasome-dependent degradation of Daxx by the viral E1B-55 K protein in human adenovirus-infected cells. J Virol. 2010; 84(14):7029-7038.
• [17]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):2137-2150.
• [18]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):4610-4618.
• [19]Geimanen J, Isok-Paas H, Pipitch R, Salk K, Laos T, Orav M, Reinson T, Ustav MJ, Ustav M, Ustav E. 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):3315-3329.
• [20]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):449-457.
• [21]Sakakibara N, Chen D, Jang M, Kang D, Luecke H, Wu S, Chiang C, McBride A. Brd4 is displaced from HPV replication factories as they expand and amplify viral DNA. PLoS Pathog. 2013; 9(11): Article ID e1003777
• [22]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):142-150.
• [23]Heino P, Zhou J, Lambert P. Interaction of the papillomavirus transcription/replication factor, E2, and the viral capsid protein, L2. Virology. 2000; 276(2):304-314.
• [24]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):159-166.
• [25]Reinson T, Toots M, Kadaja M, Pipitch R, Allik M, Ustav E, Ustav M. Engagement of the ATR-dependent DNA damage response at the human papillomavirus 18 replication centers during the initial amplification. J Virol. 2013; 87(2):951-964.
• [26]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): Article ID e116151
• [27]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. BioMed Central Full Text
• [28]Ishov A, Maul G. The periphery of nuclear domain 10 (ND10) as site of DNA virus deposition. J Cell Biol. 1996; 134(4):815-826.
• [29]Schmid M, Speiseder T, Dobner T, Gonzalez R. DNA virus replication compartments. J Virol. 2014; 88(3):1404-1420.
• [30]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): Article ID e1000397
• [31]Moody C, Laimins L. Human papillomaviruses activate the ATM DNA damage pathway for viral genome amplification upon differentiation. PLoS Pathog. 2009; 5(10): Article ID e1000605
• [32]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):8981-8995.
• [33]Anacker D, Gautam D, Gillespie K, Chappell W, Moody C. Productive replication of human papillomavirus 31 requires DNA repair factor Nbs1. J Virol. 2014; 15:8528-8544.
• [34]Everett R. Interactions between DNA viruses, ND10 and the DNA damage response. Cell Microbiol. 2006; 8(3):365-374.
• [35]Dellaire G, Ching R, Ahmed K, Jalali F, Tse K, Bristow R, Bazett-Jones D. 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.
• [36]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):5799-5803.
• [37]Chen L, Chen J. Daxx silencing sensitizes cells to multiple apoptotic pathways. Mol Cell Biol. 2003; 23:7108-7121.
• [38]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):4321-4329.
• [39]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):12051-12068.
• [40]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):3660-3665.