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Journal of Virology, June 2003, p. 7093-7100, Vol. 77, No. 12
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.12.7093-7100.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

A Domain in the C-Terminal Region of Latency-Associated Nuclear Antigen 1 of Kaposi's Sarcoma-Associated Herpesvirus Affects Transcriptional Activation and Binding to Nuclear Heterochromatin

Abel Viejo-Borbolla,1 Emrah Kati,1 Julie A. Sheldon,1 Kavita Nathan,1 Karin Mattsson,2 Laszlo Szekely,2 and Thomas F. Schulz1*

Department of Virology, Hannover Medical School, Hannover, Germany,1 Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden2

Received 29 October 2002/ Accepted 21 February 2003

The latency-associated nuclear antigen 1 (LANA-1) of Kaposi's sarcoma-associated herpesvirus (KSHV) is required for the maintenance and replication of viral episomal DNA. The binding sites for nuclear heterochromatin and transcriptional repressor complexes are located in an amino-terminal region of LANA-1, whereas those for viral episomal DNA, p53, pRB, and members of the BRD/fsh family of nuclear proteins are located in its carboxy-terminal domain. LANA-1 activates or represses several cellular and viral promoters. In this report we show that a domain of 15 amino acids (amino acids 1129 to 1143), located close to the carboxy-terminal end of LANA-1, is required for the interaction of LANA-1 with nuclear heterochromatin or nuclear matrix, and for the ability of LANA-1 to activate the Epstein-Barr virus Cp promoter. LANA-1 proteins that are tightly associated with nuclear heterochromatin or matrix differ in molecular weight from LANA-1 proteins that can be dissociated from the nuclear matrix by high-salt buffers, suggesting that posttranslational modifications may determine the association of LANA-1 with nuclear heterochromatin or matrix.

* Corresponding author. Mailing address: Department of Virology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Phone: 49-511-532-6736. Fax: 49-511-532-8736. E-mail: tschulz{at}virologie.mh-hannover.de.

Journal of Virology, June 2003, p. 7093-7100, Vol. 77, No. 12
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.12.7093-7100.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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