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Journal of Virology, November 2002, p. 11596-11604, Vol. 76, No. 22
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.22.11596-11604.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Protein Interactions Targeting the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus to Cell Chromosomes

Anita Krithivas,1 Masahiro Fujimuro,2 Magdalena Weidner,1 David B. Young,1 and S. Diane Hayward1,2*

Department of Pharmacology and Molecular Sciences,1 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland 212312

Received 13 May 2002/ Accepted 13 August 2002

Maintenance of Kaposi's sarcoma-associated herpesvirus (KSHV) latent infection depends on the viral episomes in the nucleus being distributed to daughter cells following cell division. The latency-associated nuclear antigen (LANA) is constitutively expressed in all KSHV-infected cells. LANA binds sequences in the terminal repeat regions of the KSHV genome and tethers the viral episomes to chromosomes. To better understand the mechanism of chromosomal tethering, we performed glutathione S-transferase (GST) affinity and yeast two-hybrid assays to identify LANA-interacting proteins with known chromosomal association. Two of the interactors were the methyl CpG binding protein MeCP2 and the 43-kDa protein DEK. The interactions of MeCP2 and DEK with LANA were confirmed by coimmunoprecipitation. The MeCP2-interacting domain was mapped to the previously described chromatin binding site in the N terminus of LANA, while the DEK-interacting domain mapped to LANA amino acids 986 to 1043 in the C terminus. LANA was unable to associate with mouse chromosomes in chromosome spreads of transfected NIH 3T3 cells. However, LANA was capable of targeting to mouse chromosomes in the presence of human MeCP2 or DEK. The data indicate that LANA is tethered to chromosomes through two independent chromatin binding domains that interact with different protein partners.

* Corresponding author. Mailing address: Sidney Kimmel Comprehensive Cancer Center, Bunting-Blaustein Building CRB308, Johns Hopkins School of Medicine, 1650 Orleans St., Baltimore, MD 21231. Phone: (410) 955-2548. Fax: (410) 502-6802. E-mail: dhayward{at}jhmi.edu.

Journal of Virology, November 2002, p. 11596-11604, Vol. 76, No. 22
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.22.11596-11604.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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