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Journal of Virology, November 2005, p. 13618-13629, Vol. 79, No. 21
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.21.13618-13629.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Brd2/RING3 Interacts with a Chromatin-Binding Domain in the Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 (LANA-1) That Is Required for Multiple Functions of LANA-1

Abel Viejo-Borbolla,{dagger} Matthias Ottinger, Eva Brüning, Antje Bürger, Regina König, Emrah Kati, Julie A. Sheldon,{ddagger} and Thomas F. Schulz*

Department of Virology, Hannover Medical School, Hannover, Germany

Received 13 May 2005/ Accepted 5 August 2005

Latency-associated nuclear antigen 1 (LANA-1) of Kaposi's sarcoma-associated herpesvirus (KSHV) mediates the episomal replication of the KSHV genome, as well as transcriptional regulation, in latently infected cells. Interaction of LANA-1 with cellular chromatin is required for both these functions. An N-terminal heterochromatin-binding site in LANA-1 is essential for the replication and maintenance of latent episomes, as well as transcriptional regulation. We have recently described a C-terminal domain in LANA-1 that modulates the interaction with cellular interphase chromatin or elements of the nuclear matrix. Here, we used a series of LANA-1 deletion mutants to investigate the relationship between the different functions of LANA-1 and its interaction with the host chromatin-binding protein Brd2/RING3. Our findings suggest that the C-terminal chromatin-binding domain in LANA-1 is required for multiple LANA-1 functions, including the ability to bind to and replicate viral episomal DNA, to modulate transcription, and to interact with Brd2/RING3. Similar to the recently described tethering of bovine papillomavirus E2 protein to host chromatin via Brd4/MCAP, Brd2/RING3, another member of the Brd family of chromatin-binding proteins, therefore interacts with a chromatin-binding region of another viral latent nuclear protein and could play a role in its multiple functions.

* 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 6736. E-mail: schulz.thomas{at}mh-hannover.de.

{dagger} Present address: Department of Cell and Molecular Biology, Centro Nacional de Biotecnología, CSIC, Madrid, Spain.

{ddagger} Present address: Centro de Salud Carlos III, Madrid, Spain.

Journal of Virology, November 2005, p. 13618-13629, Vol. 79, No. 21
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.21.13618-13629.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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