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.
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 (DeltaN-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 DeltaN-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.
Shinohara
Hirohiko
H
Divisions of Virology. Thoracic and Cardiovascular Surgery, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-Dori, Niigata 951-8510, Japan.
Fukushi
Masaya
M
Higuchi
Masaya
M
Oie
Masayasu
M
Hoshi
Osamu
O
Ushiki
Tatsuo
T
Hayashi
Jun-Ichi
J
Fujii
Masahiro
M
D000956:Antigens, Viral; D001665:Binding Sites; D002352:Carrier Proteins / Q000502:physiology; D002877:Chromosomes, Human / Q000378:metabolism*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000502:physiology; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006657:Histones / Q000502:physiology*; D006801:Humans; D008938:Mitosis; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D010957:Plasmids; D016601:RNA-Binding Proteins; D014407:Tumor Cells, Cultured
D000956:Antigens, Viral; D002352:Carrier Proteins; C432687:EBNA1BP2 protein, human; D019309:Epstein-Barr Virus Nuclear Antigens; D006657:Histones; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C109540:latency-associated nuclear antigen; C417029:EBV-encoded nuclear antigen 1