1. A short sequence immediately upstream of the internal repeat elements is critical for KSHV LANA mediated DNA replication and impacts episome persistence
- Author
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Erika De León Vázquez, Franceline Juillard, Kenneth M. Kaye, and Bernard Rosner
- Subjects
DNA Replication ,Heterochromatin ,LANA ,viruses ,Molecular Sequence Data ,KSHV ,Biology ,Virus Replication ,Article ,Cell Line ,03 medical and health sciences ,Plasmid ,Virology ,Humans ,Amino Acid Sequence ,Nuclear protein ,Peptide sequence ,Antigens, Viral ,030304 developmental biology ,Genetics ,0303 health sciences ,030302 biochemistry & molecular biology ,DNA replication ,Terminal Repeat Sequences ,virus diseases ,Nuclear Proteins ,Herpesviridae Infections ,biochemical phenomena, metabolism, and nutrition ,Chromatin ,Viral replication ,Cell culture ,Herpesvirus 8, Human ,Episome persistence ,Plasmids - Abstract
Kaposi's sarcoma-associated herpesvirus LANA (1162 residues) mediates episomal persistence of viral genomes during latency. LANA mediates viral DNA replication and segregates episomes to daughter nuclei. A 59 residue deletion immediately upstream of the internal repeat elements rendered LANA highly deficient for DNA replication and modestly deficient for the ability to segregate episomes, while smaller deletions did not. The 59 amino acid deletion reduced LANA episome persistence by ~14-fold, while sequentially smaller deletions resulted in ~3-fold, or no deficiency. Three distinct LANA regions reorganized heterochromatin, one of which contains the deleted sequence, but the deletion did not abolish LANA's ability to alter chromatin. Therefore, this work identifies a short internal LANA sequence that is critical for DNA replication, has modest effects on episome segregation, and substantially impacts episome persistence; this region may exert its effects through an interacting host cell protein(s).
- Published
- 2013