Previous Article | Next Article 
Journal of Virology, May 1999, p. 4404-4412, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Long-Term Episomal Maintenance of Bovine
Papillomavirus Type 1 Plasmids Is Determined by Attachment to Host
Chromosomes, Which Is Mediated by the Viral E2 Protein and Its
Binding Sites
Ivar
Ilves,1
Sirje
Kivi,2 and
Mart
Ustav1,*
Department of Microbiology and
Virology1 and Department of Cell
Biology,2 Institute of Molecular and Cell
Biology, Estonian Biocentre, Tartu University, 51010 Tartu, Estonia
Received 21 October 1998/Accepted 19 January 1999
Papillomavirus genomes are stably maintained as extrachromosomal
nuclear plasmids in dividing host cells. To address the mechanisms responsible for stable maintenance of virus, we examined nuclear compartmentalization of plasmids containing the full-length upstream regulatory region (URR) from the bovine papillomavirus type 1 (BPV1)
genome. We found that these plasmids are tightly associated with the
nuclear chromatin both in the stable cell lines that maintain episomal
copies of the plasmids and in transiently transfected cells expressing
the viral E1 and E2 proteins. Further analysis of viral factors
revealed that the E2 protein in trans and its multiple
binding sites in cis are both necessary and sufficient for
the chromatin attachment of the plasmids. On the other hand, the BPV1
URR-dependent plasmid replication and chromatin attachment processes
are clearly independent of each other. The ability of the plasmids to
stably maintain episomes correlates clearly with their chromatin
association function. These data suggest that viral E2 protein-mediated
attachment of BPV1 genomes to the host cell chromatin could provide a
mechanism for the coupling of viral genome multiplication and
partitioning to the host cell cycle during viral latent infection.
*
Corresponding author. Mailing address: Department of
Microbiology and Virology, Institute of Molecular and Cell Biology,
Tartu University, 23 Riia St., Tartu 51010, Estonia. Phone:
372-7-375047. Fax: 372-7-420286. E-mail: ustav{at}ebc.ee.
Journal of Virology, May 1999, p. 4404-4412, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Feeney, K. M, Parish, J. L
(2009). Targeting mitotic chromosomes: a conserved mechanism to ensure viral genome persistence. Proc R Soc B
276: 1535-1544
[Abstract]
[Full Text]
-
Jang, M. K., Kwon, D., McBride, A. A.
(2009). Papillomavirus E2 Proteins and the Host Brd4 Protein Associate with Transcriptionally Active Cellular Chromatin. J. Virol.
83: 2592-2600
[Abstract]
[Full Text]
-
Poddar, A., Reed, S. C., McPhillips, M. G., Spindler, J. E., McBride, A. A.
(2009). The Human Papillomavirus Type 8 E2 Tethering Protein Targets the Ribosomal DNA Loci of Host Mitotic Chromosomes. J. Virol.
83: 640-650
[Abstract]
[Full Text]
-
Lin, A., Wang, S., Nguyen, T., Shire, K., Frappier, L.
(2008). The EBNA1 Protein of Epstein-Barr Virus Functionally Interacts with Brd4. J. Virol.
82: 12009-12019
[Abstract]
[Full Text]
-
Schweiger, M.-R., Ottinger, M., You, J., Howley, P. M.
(2007). Brd4-Independent Transcriptional Repression Function of the Papillomavirus E2 Proteins. J. Virol.
81: 9612-9622
[Abstract]
[Full Text]
-
Kelley-Clarke, B., Ballestas, M. E., Srinivasan, V., Barbera, A. J., Komatsu, T., Harris, T.-A., Kazanjian, M., Kaye, K. M.
(2007). Determination of Kaposi's Sarcoma-Associated Herpesvirus C-Terminal Latency-Associated Nuclear Antigen Residues Mediating Chromosome Association and DNA Binding. J. Virol.
81: 4348-4356
[Abstract]
[Full Text]
-
Ajay Kumar, R., Naidu, S. R., Wang, X., Imbalzano, A. N., Androphy, E. J.
(2007). Interaction of Papillomavirus E2 Protein with the Brm Chromatin Remodeling Complex Leads to Enhanced Transcriptional Activation. J. Virol.
81: 2213-2220
[Abstract]
[Full Text]
-
Yu, T., Peng, Y.-C., Androphy, E. J.
(2007). Mitotic Kinesin-Like Protein 2 Binds and Colocalizes with Papillomavirus E2 during Mitosis. J. Virol.
81: 1736-1745
[Abstract]
[Full Text]
-
McPhillips, M. G., Oliveira, J. G., Spindler, J. E., Mitra, R., McBride, A. A.
(2006). Brd4 Is Required for E2-Mediated Transcriptional Activation but Not Genome Partitioning of All Papillomaviruses. J. Virol.
80: 9530-9543
[Abstract]
[Full Text]
-
You, J., Srinivasan, V., Denis, G. V., Harrington, W. J. Jr., Ballestas, M. E., Kaye, K. M., Howley, P. M.
(2006). Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Interacts with Bromodomain Protein Brd4 on Host Mitotic Chromosomes.. J. Virol.
80: 8909-8919
[Abstract]
[Full Text]
-
Wu, S.-Y., Lee, A-Y., Hou, S. Y., Kemper, J. K., Erdjument-Bromage, H., Tempst, P., Chiang, C.-M.
(2006). Brd4 links chromatin targeting to HPV transcriptional silencing. Genes Dev.
20: 2383-2396
[Abstract]
[Full Text]
-
Schweiger, M.-R., You, J., Howley, P. M.
(2006). Bromodomain Protein 4 Mediates the Papillomavirus E2 Transcriptional Activation Function. J. Virol.
80: 4276-4285
[Abstract]
[Full Text]
-
Dao, L. D., Duffy, A., Van Tine, B. A., Wu, S.-Y., Chiang, C.-M., Broker, T. R., Chow, L. T.
(2006). Dynamic Localization of the Human Papillomavirus Type 11 Origin Binding Protein E2 through Mitosis While in Association with the Spindle Apparatus.. J. Virol.
80: 4792-4800
[Abstract]
[Full Text]
-
Ilves, I., Maemets, K., Silla, T., Janikson, K., Ustav, M.
(2006). Brd4 is involved in multiple processes of the bovine papillomavirus type 1 life cycle.. J. Virol.
80: 3660-3665
[Abstract]
[Full Text]
-
Oliveira, J. G., Colf, L. A., McBride, A. A.
(2006). Variations in the association of papillomavirus E2 proteins with mitotic chromosomes. Proc. Natl. Acad. Sci. USA
103: 1047-1052
[Abstract]
[Full Text]
-
Silla, T., Haal, I., Geimanen, J., Janikson, K., Abroi, A., Ustav, E., Ustav, M.
(2005). Episomal Maintenance of Plasmids with Hybrid Origins in Mouse Cells. J. Virol.
79: 15277-15288
[Abstract]
[Full Text]
-
You, J., Schweiger, M.-R., Howley, P. M.
(2005). Inhibition of E2 Binding to Brd4 Enhances Viral Genome Loss and Phenotypic Reversion of Bovine Papillomavirus-Transformed Cells. J. Virol.
79: 14956-14961
[Abstract]
[Full Text]
-
Kurg, R., Sild, K., Ilves, A., Sepp, M., Ustav, M.
(2005). Association of Bovine Papillomavirus E2 Protein with Nuclear Structures In Vivo. J. Virol.
79: 10528-10539
[Abstract]
[Full Text]
-
McPhillips, M. G., Ozato, K., McBride, A. A.
(2005). Interaction of Bovine Papillomavirus E2 Protein with Brd4 Stabilizes Its Association with Chromatin. J. Virol.
79: 8920-8932
[Abstract]
[Full Text]
-
Baxter, M. K., McPhillips, M. G., Ozato, K., McBride, A. A.
(2005). The Mitotic Chromosome Binding Activity of the Papillomavirus E2 Protein Correlates with Interaction with the Cellular Chromosomal Protein, Brd4. J. Virol.
79: 4806-4818
[Abstract]
[Full Text]
-
Brannon, A. R., Maresca, J. A., Boeke, J. D., Basrai, M. A., McBride, A. A.
(2005). Reconstitution of papillomavirus E2-mediated plasmid maintenance in Saccharomyces cerevisiae by the Brd4 bromodomain protein. Proc. Natl. Acad. Sci. USA
102: 2998-3003
[Abstract]
[Full Text]
-
Zheng, P.-S., Brokaw, J., McBride, A. A.
(2005). Conditional Mutations in the Mitotic Chromosome Binding Function of the Bovine Papillomavirus Type 1 E2 Protein. J. Virol.
79: 1500-1509
[Abstract]
[Full Text]
-
Srinivasan, V., Komatsu, T., Ballestas, M. E., Kaye, K. M.
(2004). Definition of Sequence Requirements for Latency-Associated Nuclear Antigen 1 Binding to Kaposi's Sarcoma-Associated Herpesvirus DNA. J. Virol.
78: 14033-14038
[Abstract]
[Full Text]
-
Lim, C., Choi, C., Choe, J.
(2004). Mitotic Chromosome-Binding Activity of Latency-Associated Nuclear Antigen 1 Is Required for DNA Replication from Terminal Repeat Sequence of Kaposi's Sarcoma-Associated Herpesvirus. J. Virol.
78: 7248-7256
[Abstract]
[Full Text]
-
Penrose, K. J., Garcia-Alai, M., de Prat-Gay, G., McBride, A. A.
(2004). Casein Kinase II Phosphorylation-induced Conformational Switch Triggers Degradation of the Papillomavirus E2 Protein. J. Biol. Chem.
279: 22430-22439
[Abstract]
[Full Text]
-
Van Tine, B. A., Dao, L. D., Wu, S.-Y., Sonbuchner, T. M., Lin, B. Y., Zou, N., Chiang, C.-M., Broker, T. R., Chow, L. T.
(2004). Human papillomavirus (HPV) origin-binding protein associates with mitotic spindles to enable viral DNA partitioning. Proc. Natl. Acad. Sci. USA
101: 4030-4035
[Abstract]
[Full Text]
-
Mechali, F., Hsu, C.-Y., Castro, A., Lorca, T., Bonne-Andrea, C.
(2004). Bovine Papillomavirus Replicative Helicase E1 Is a Target of the Ubiquitin Ligase APC. J. Virol.
78: 2615-2619
[Abstract]
[Full Text]
-
Abroi, A., Ilves, I., Kivi, S., Ustav, M.
(2004). Analysis of Chromatin Attachment and Partitioning Functions of Bovine Papillomavirus Type 1 E2 Protein. J. Virol.
78: 2100-2113
[Abstract]
[Full Text]
-
Barbera, A. J., Ballestas, M. E., Kaye, K. M.
(2004). The Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 N Terminus Is Essential for Chromosome Association, DNA Replication, and Episome Persistence. J. Virol.
78: 294-301
[Abstract]
[Full Text]
-
Deng, W., Jin, G., Lin, B.-Y., Van Tine, B. A., Broker, T. R., Chow, L. T.
(2003). mRNA Splicing Regulates Human Papillomavirus Type 11 E1 Protein Production and DNA Replication. J. Virol.
77: 10213-10226
[Abstract]
[Full Text]
-
Kapoor, P., Frappier, L.
(2003). EBNA1 Partitions Epstein-Barr Virus Plasmids in Yeast Cells by Attaching to Human EBNA1-Binding Protein 2 on Mitotic Chromosomes. J. Virol.
77: 6946-6956
[Abstract]
[Full Text]
-
Hou, S. Y., Wu, S.-Y., Chiang, C.-M.
(2002). Transcriptional Activity among High and Low Risk Human Papillomavirus E2 Proteins Correlates with E2 DNA Binding. J. Biol. Chem.
277: 45619-45629
[Abstract]
[Full Text]
-
Jeckel, S., Huber, E., Stubenrauch, F., Iftner, T.
(2002). A Transactivator Function of Cottontail Rabbit Papillomavirus E2 Is Essential for Tumor Induction in Rabbits. J. Virol.
76: 11209-11215
[Abstract]
[Full Text]
-
Malcles, M.-H., Cueille, N., Mechali, F., Coux, O., Bonne-Andrea, C.
(2002). Regulation of Bovine Papillomavirus Replicative Helicase E1 by the Ubiquitin-Proteasome Pathway. J. Virol.
76: 11350-11358
[Abstract]
[Full Text]
-
Mehta, S., Yang, X. M., Chan, C. S., Dobson, M. J., Jayaram, M., Velmurugan, S.
(2002). The 2 micron plasmid purloins the yeast cohesin complex: a mechanism for coupling plasmid partitioning and chromosome segregation?. JCB
158: 625-637
[Abstract]
[Full Text]
-
Boner, W., Taylor, E. R., Tsirimonaki, E., Yamane, K., Campo, M. S., Morgan, I. M.
(2002). A Functional Interaction between the Human Papillomavirus 16 Transcription/Replication Factor E2 and the DNA Damage Response Protein TopBP1. J. Biol. Chem.
277: 22297-22303
[Abstract]
[Full Text]
-
Mannik, A., Runkorg, K., Jaanson, N., Ustav, M., Ustav, E.
(2002). Induction of the Bovine Papillomavirus Origin "Onion Skin"-Type DNA Replication at High E1 Protein Concentrations In Vivo. J. Virol.
76: 5835-5845
[Abstract]
[Full Text]
-
Angeletti, P. C., Kim, K., Fernandes, F. J., Lambert, P. F.
(2002). Stable Replication of Papillomavirus Genomes in Saccharomyces cerevisiae. J. Virol.
76: 3350-3358
[Abstract]
[Full Text]
-
Voitenleitner, C., Botchan, M.
(2002). E1 Protein of Bovine Papillomavirus Type 1 Interferes with E2 Protein-Mediated Tethering of the Viral DNA to Mitotic Chromosomes. J. Virol.
76: 3440-3451
[Abstract]
[Full Text]
-
Kanda, T., Otter, M., Wahl, G. M.
(2001). Coupling of Mitotic Chromosome Tethering and Replication Competence in Epstein-Barr Virus-Based Plasmids. Mol. Cell. Biol.
21: 3576-3588
[Abstract]
[Full Text]
-
Ballestas, M. E., Kaye, K. M.
(2001). Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 Mediates Episome Persistence through cis-Acting Terminal Repeat (TR) Sequence and Specifically Binds TR DNA. J. Virol.
75: 3250-3258
[Abstract]
[Full Text]
-
Hung, S. C., Kang, M.-S., Kieff, E.
(2001). Maintenance of Epstein-Barr virus (EBV) oriP-based episomes requires EBV-encoded nuclear antigen-1 chromosome-binding domains, which can be replaced by high-mobility group-I or histone H1. Proc. Natl. Acad. Sci. USA
10.1073/pnas.031584698v1
[Abstract]
[Full Text]
-
Kanda, T, Otter, M, Wahl, G.
(2001). Mitotic segregation of viral and cellular acentric extrachromosomal molecules by chromosome tethering. J. Cell Sci.
114: 49-58
[Abstract]
-
Penrose, K. J., McBride, A. A.
(2000). Proteasome-Mediated Degradation of the Papillomavirus E2-TA Protein Is Regulated by Phosphorylation and Can Modulate Viral Genome Copy Number. J. Virol.
74: 6031-6038
[Abstract]
[Full Text]
-
Velmurugan, S., Yang, X.-M., Chan, C. S.-M., Dobson, M., Jayaram, M.
(2000). Partitioning of the 2-{micro}m Circle Plasmid of Saccharomyces cerevisiae: Functional Coordination with Chromosome Segregation and Plasmid-Encoded Rep Protein Distribution. JCB
149: 553-566
[Abstract]
[Full Text]
-
Zou, N., Lin, B. Y., Duan, F., Lee, K.-Y., Jin, G., Guan, R., Yao, G., Lefkowitz, E. J., Broker, T. R., Chow, L. T.
(2000). The Hinge of the Human Papillomavirus Type 11 E2 Protein Contains Major Determinants for Nuclear Localization and Nuclear Matrix Association. J. Virol.
74: 3761-3770
[Abstract]
[Full Text]
-
Kurg, R., Parik, J., Juronen, E., Sedman, T., Abroi, A., Liiv, I., Langel, U., Ustav, M.
(1999). Effect of Bovine Papillomavirus E2 Protein-Specific Monoclonal Antibodies on Papillomavirus DNA Replication. J. Virol.
73: 4670-4677
[Abstract]
[Full Text]
-
Fujii, T., Brandsma, J. L., Peng, X., Srimatkandada, S., Li, L., Canaan, A., Deisseroth, A. B.
(2001). High and Low Levels of Cottontail Rabbit Papillomavirus E2 Protein Generate Opposite Effects on Gene Expression. J. Biol. Chem.
276: 867-874
[Abstract]
[Full Text]
-
Hung, S. C., Kang, M.-S., Kieff, E.
(2001). Maintenance of Epstein-Barr virus (EBV) oriP-based episomes requires EBV-encoded nuclear antigen-1 chromosome-binding domains, which can be replaced by high-mobility group-I or histone H1. Proc. Natl. Acad. Sci. USA
98: 1865-1870
[Abstract]
[Full Text]