Identification of a virus trans-acting regulatory element on the latent DNA replication of Kaposi's sarcoma-associated herpesvirus.
Latency-associated nuclear antigen 1 (LANA1) of Kaposi's sarcoma-associated herpesvirus (KSHV) plays a pivotal role in the maintenance of the virus genome in latently infected cells. LANA1 links virus genomes to host chromosomes via a C-terminal DNA-binding domain which interacts with the sequences located in terminal repeats (TRs) of the virus genome and via an N-terminal chromosome-binding sequence which associates with the host chromosomes, respectively. Recent data suggest that LANA1 also actively participates in the replication of KSHV TR-containing plasmid in the transient DNA replication assay. In this report, it was found that C33A and COS-1, but not NIH/3T3, cell lines are permissive for the transient replication of KSHV TR-containing plasmid. Using several LANA1-deletion mutants, the minimum domain of LANA1 required for replication activity was also determined. In addition, the N terminus of LANA1 inhibited the transient replication systems of KSHV and Epstein-Barr virus (EBV) in transiently transfected 293 and 293T cells, but the C terminus of LANA1 specifically inhibited the transient replication system of KSHV in other cell lines. Consistent with previous reports, these data further emphasize the functional importance of the N terminus of LANA1 on replication from the KSHV latent origin of DNA replication.
Lim
Chunghun
C
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Seo
Taegun
T
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Jung
Jun
J
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Choe
Joonho
J
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral; D019556:COS Cells; D002460:Cell Line; D004261:DNA Replication / Q000235:genetics* / Q000502:physiology*; D005809:Genes, Regulator; D005814:Genes, Viral; D019288:Herpesvirus 8, Human / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D010957:Plasmids / Q000235:genetics; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D020079:Terminal Repeat Sequences; D014162:Transfection; D014779:Virus Replication / Q000235:genetics / Q000502:physiology
D000956:Antigens, Viral; D009687:Nuclear Proteins; C109540:latency-associated nuclear antigen