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.
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.
Cotter
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Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Subramanian
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C
Robertson
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D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus; D016384:Consensus Sequence; D004279:DNA, Viral; D015870:Gene Expression; D016679:Genome, Viral; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011233:Precipitin Tests; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D012514:Sarcoma, Kaposi / Q000821:virology; D016415:Sequence Alignment; D014407:Tumor Cells, Cultured
D000956:Antigens, Viral; D004279:DNA, Viral; D009687:Nuclear Proteins; C109540:latency-associated nuclear antigen