This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Daikoku, T. Articles by Tsurumi, T. Search for Related Content PubMed PubMed Citation Articles by Daikoku, T. Articles by Tsurumi, T.

 Previous Article  |  Next Article 

Journal of Virology, March 2005, p. 3409-3418, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3409-3418.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Architecture of Replication Compartments Formed during Epstein-Barr Virus Lytic Replication

Tohru Daikoku,^1, Ayumi Kudoh,^1, Masatoshi Fujita,² Yutaka Sugaya,¹ Hiroki Isomura,¹ Noriko Shirata,¹ and Tatsuya Tsurumi^1*

Division of Virology, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya,¹ Virology Division, National Cancer Center Research Institute, Chuohku, Tokyo, Japan²

Received 26 July 2004/ Accepted 28 October 2004

Epstein-Barr virus (EBV) productive DNA replication occurs at discrete sites, called replication compartments, in nuclei. In this study we performed comprehensive analyses of the architecture of the replication compartments. The BZLF1 oriLyt binding proteins showed a fine, diffuse pattern of distribution throughout the nuclei at immediate-early stages of induction and then became associated with the replicating EBV genome in the replication compartments during lytic infection. The BMRF1 polymerase (Pol) processivity factor showed a homogenous, not dot-like, distribution in the replication compartments, which completely coincided with the newly synthesized viral DNA. Inhibition of viral DNA replication with phosphonoacetic acid, a viral DNA Pol inhibitor, eliminated the DNA-bound form of the BMRF1 protein, although the protein was sufficiently expressed in the cells. These observations together with the findings that almost all abundantly expressed BMRF1 proteins existed in the DNA-bound form suggest that the BMRF1 proteins not only act at viral replication forks as Pol processive factors but also widely distribute on newly replicated EBV genomic DNA. In contrast, the BALF5 Pol catalytic protein, the BALF2 single-stranded-DNA binding protein, and the BBLF2/3 protein, a component of the helicase-primase complex, were colocalized as distinct dots distributed within replication compartments, representing viral replication factories. Whereas cellular replication factories are constructed based on nonchromatin nuclear structures and nuclear matrix, viral replication factories were easily solubilized by DNase I treatment. Thus, compared with cellular DNA replication, EBV lytic DNA replication factories would be simpler so that construction of the replication domain would be more relaxed.

T.D. and A.K. contributed equally to this work.

This article has been cited by other articles:

• Qian, Z., Xuan, B., Hong, T. T., Yu, D. (2008). The Full-Length Protein Encoded by Human Cytomegalovirus Gene UL117 Is Required for the Proper Maturation of Viral Replication Compartments. J. Virol. 82: 3452-3465 [Abstract] [Full Text]  
• Gill, M. B., Kutok, J. L., Fingeroth, J. D. (2007). Epstein-Barr Virus Thymidine Kinase Is a Centrosomal Resident Precisely Localized to the Periphery of Centrioles. J. Virol. 81: 6523-6535 [Abstract] [Full Text]  
• Kudoh, A., Daikoku, T., Ishimi, Y., Kawaguchi, Y., Shirata, N., Iwahori, S., Isomura, H., Tsurumi, T. (2006). Phosphorylation of MCM4 at Sites Inactivating DNA Helicase Activity of the MCM4-MCM6-MCM7 Complex during Epstein-Barr Virus Productive Replication.. J. Virol. 80: 10064-10072 [Abstract] [Full Text]  
• Amon, W., White, R. E., Farrell, P. J. (2006). Epstein-Barr virus origin of lytic replication mediates association of replicating episomes with promyelocytic leukaemia protein nuclear bodies and replication compartments.. J. Gen. Virol. 87: 1133-1137 [Abstract] [Full Text]  
• Neuhierl, B., Delecluse, H.-J. (2006). The Epstein-Barr Virus BMRF1 Gene Is Essential for Lytic Virus Replication.. J. Virol. 80: 5078-5081 [Abstract] [Full Text]  
• Daikoku, T., Kudoh, A., Sugaya, Y., Iwahori, S., Shirata, N., Isomura, H., Tsurumi, T. (2006). Postreplicative Mismatch Repair Factors Are Recruited to Epstein-Barr Virus Replication Compartments. J. Biol. Chem. 281: 11422-11430 [Abstract] [Full Text]  
• Wang, J.-T., Yang, P.-W., Lee, C.-P., Han, C.-H., Tsai, C.-H., Chen, M.-R. (2005). Detection of Epstein-Barr virus BGLF4 protein kinase in virus replication compartments and virus particles. J. Gen. Virol. 86: 3215-3225 [Abstract] [Full Text]  
• Shirata, N., Kudoh, A., Daikoku, T., Tatsumi, Y., Fujita, M., Kiyono, T., Sugaya, Y., Isomura, H., Ishizaki, K., Tsurumi, T. (2005). Activation of Ataxia Telangiectasia-mutated DNA Damage Checkpoint Signal Transduction Elicited by Herpes Simplex Virus Infection. J. Biol. Chem. 280: 30336-30341 [Abstract] [Full Text]