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Journal of Virology, April 2001, p. 3948-3959, Vol. 75, No. 8
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.8.3948-3959.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Close but Distinct Regions of Human Herpesvirus 8 Latency-Associated Nuclear Antigen 1 Are Responsible for Nuclear Targeting and Binding to Human Mitotic Chromosomes

Tristan Piolot,1 Marc Tramier,2 Maité Coppey,2 Jean-Claude Nicolas,1 and Vincent Marechal1,*

Service de Microbiologie---EA 2391, Hôpital Rothschild, 75571 Paris Cedex 12,1 and Institut Jacques Monod, 75251 Paris Cedex 05,2 France

Received 3 October 2000/Accepted 15 January 2001

Human herpesvirus 8 is associated with all forms of Kaposi's sarcoma, AIDS-associated body cavity-based lymphomas, and some forms of multicentric Castleman's disease. Herpesvirus 8, like other gammaherpesviruses, can establish a latent infection in which viral genomes are stably maintained as multiple episomes. The latent nuclear antigen (LANA or LNAI) may play an essential role in the stable maintenance of latent episomes, notably by interacting concomitantly with the viral genomes and the metaphase chromosomes, thus ensuring an efficient transmission of the neoduplicated episomes to the daughter cells. To identify the regions responsible for its nuclear and subnuclear localization in interphase and mitotic cells, LNAI and various truncated forms were fused to a variant of green fluorescent protein. This enabled their localization and chromosome binding activity to be studied by low-light-level fluorescence microscopy in living HeLa cells. The results demonstrate that nuclear localization of LNAI is due to a unique signal, which maps between amino acids 24 and 30. Interestingly, this nuclear localization signal closely resembles those identified in EBNA1 from Epstein-Barr virus and herpesvirus papio. A region encompassing amino acids 5 to 22 was further proved to mediate the specific interaction of LNA1 with chromatin during interphase and the chromosomes during mitosis. The presence of putative phosphorylation sites in the chromosome binding sites of LNA1 and EBNA1 suggests that their activity may be regulated by specific cellular kinases.

* Corresponding author. Mailing address: Service de Microbiologie---EA 2391, Hôpital Rothschild, 33 Blvd. de Picpus, 75571 Paris Cedex 12, France. Phone: (33) 1 40 19 35 53. Fax: (33) 1 40 19 33 35. E-mail: vincent.marechal{at}rth.ap-hop-paris.fr.

Journal of Virology, April 2001, p. 3948-3959, Vol. 75, No. 8
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.8.3948-3959.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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