title: A short sequence immediately upstream of the internal repeat elements is critical for KSHV LANA mediated DNA replication and impacts episome persistence.
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).
authors: Departments of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, United States.
authors: Erika
authors: E
authors: De León Vázquez
authors: Franceline
authors: F
authors: Juillard
authors: Bernard
authors: B
authors: Rosner
authors: Kenneth M
authors: KM
authors: Kaye
mesh_terms: D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D004261:DNA Replication; D006566:Herpesviridae Infections / Q000378:metabolism / Q000821:virology*; D019288:Herpesvirus 8, Human / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics*; D020079:Terminal Repeat Sequences; D014779:Virus Replication
chemical_list: D000956:Antigens, Viral; D002843:Chromatin; D009687:Nuclear Proteins; C109540:latency-associated nuclear antigen
keywords: DNA replication; Episome persistence; KSHV; LANA