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Journal of Virology, December 2002, p. 12917-12924, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12917-12924.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Chromosome Binding Site of Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus Is Essential for Persistent Episome Maintenance and Is Functionally Replaced by Histone H1

Hirohiko Shinohara,1,2 Masaya Fukushi,1 Masaya Higuchi,1 Masayasu Oie,1 Osamu Hoshi,3 Tatsuo Ushiki,3 Jun-Ichi Hayashi,2 and Masahiro Fujii1*

Divisions of Virology,1 Thoracic and Cardiovascular Surgery,2 Anatomy and Histology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan3

Received 21 March 2002/ Accepted 11 September 2002

Latency-associated nuclear antigen 1 (LANA1) of Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus 8) persistently maintains a plasmid containing the KSHV latent origin of replication (oriP) as a closed circular episome in dividing cells. In this study, we investigated the involvement of chromosome binding activity of LANA1 in persistent episome maintenance. Deletion of the N-terminal 22 amino acids of LANA1 ({Delta}N-LANA) inhibited the interaction with mitotic chromosomes in a human cell line, and the mutant concomitantly lost activity for the long-term episome maintenance of a plasmid containing viral oriP in a human B-cell line. However, a chimera of {Delta}N-LANA with histone H1, a cellular chromosome component protein, rescued the association with mitotic chromosomes as well as the long-term episome maintenance of the oriP-containing plasmid. Our results suggest that tethering of KSHV episomes to mitotic chromosomes by LANA1 is crucial in mediating the long-term maintenance of viral episomes in dividing cells.

* Corresponding author. Mailing address: Division of Virology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-Dori, Niigata 951-8510, Japan. Phone: 81 (25) 227-2115. Fax: 81 (25) 227-0763. E-mail: fujiimas{at}med.niigata-u.ac.jp.

Journal of Virology, December 2002, p. 12917-12924, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12917-12924.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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