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Virology. 2001 Dec 20;291(2):241-59.

The Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen binds to specific sequences at the left end of the viral genome through its carboxy-terminus.

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  • 1Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Abstract

Latent infection by members of the gammaherpesvirus family is typically characterized by stable episomal maintenance of genomic viral DNA. In the case of Epstein--Barr virus (EBV), this is dependent upon binding of the Epstein-Barr nuclear antigen 1 (EBNA1) to sites which lie within the origin of plasmid replication (OriP). The recently discovered Kaposi's sarcoma-associated herpesvirus (KSHV) encodes the latency-associated nuclear antigen (LANA), which appears to be important for supporting the latent infection of human cells by KSHV. The present work describes site-specific binding of the LANA protein to multiple different elements at the left end of the genome, a region which appears to be critical for maintenance of KSHV episomes. Of the three sites, terminal LANA-binding region 4 (TLBR4) binds LANA with the highest affinity when compared to the other sites. Further characterization of this cis-acting element by mutagenesis studies indicates that the minimal TLBR4-binding sequence is represented by a 13-bp sequence 5prime prime or minute CGCCCGGGCATGG 3prime prime or minute. Furthermore, this specific binding to TLBR4 was mediated by the distal 200 amino acid C-terminus of the LANA protein.

(C)2001 Elsevier Science.

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