Latent nuclear antigen of Kaposi's sarcoma herpesvirus/human herpesvirus-8 induces and relocates RING3 to nuclear heterochromatin regions.
LANA, the major latency-associated nuclear antigen of Kaposi's sarcoma herpesvirus/human herpesvirus-8 (KSHV/HHV-8), binds RING3 protein, one of five human homologues of the fsh (female sterile homeotic) gene product of Drosophila. In KSHV/HHV-8-infected cells LANA and the viral episomes accumulate in heterochromatin-associated nuclear bodies. Here we show that in several KSHV/HHV-8-negative cell lines derived from carcinomas, sarcomas and lymphomas, RING3 was expressed at low levels, primarily localized to the euchromatin, and dissociated from the chromosomes during mitosis. In contrast, in KSHV/HHV-8-infected body cavity lymphoma cells the bulk of RING3 localizes to the LANA nuclear bodies and remains associated with the chromosomes during cell division. KSHV/HHV-8-infected body cavity lymphoma cells expressed RING3 at much higher levels than cells without the virus. Transfection of full-length LANA, but not the C terminus alone, greatly induced RING3 gene expression, and LANA and RING3 co-localized even in the transfected cells, in the absence of KSHV/HHV-8 viral DNA. High levels of LANA expression led to the disappearance of heterochromatin in both human and mouse cells. We suggest that LANA and RING3 may create a local euchromatic microenvironment around the viral episomes that are anchored to the heterochromatin.
Mattsson
Karin
K
Microbiology and Tumor Biology Center, Karolinska Institute, PO Box 280, S-171 77, Stockholm, Sweden1.
Kiss
Csaba
C
Microbiology and Tumor Biology Center, Karolinska Institute, PO Box 280, S-171 77, Stockholm, Sweden1.
Platt
Georgina M
GM
Molecular Virology Group, Department of Medical Microbiology, The University of Liverpool, UK3.
Simpson
Guy R
GR
Molecular Virology Group, Department of Medical Microbiology, The University of Liverpool, UK3.
Kashuba
Elena
E
Microbiology and Tumor Biology Center, Karolinska Institute, PO Box 280, S-171 77, Stockholm, Sweden1.
Klein
George
G
Microbiology and Tumor Biology Center, Karolinska Institute, PO Box 280, S-171 77, Stockholm, Sweden1.
Schulz
Thomas F
TF
Molecular Virology Group, Department of Medical Microbiology, The University of Liverpool, UK3.|Department of Virology, Hannover Medical School, D-30623 Hannover, Germany2.
Szekely
Laszlo
L
Microbiology and Tumor Biology Center, Karolinska Institute, PO Box 280, S-171 77, Stockholm, Sweden1.
D021581:Active Transport, Cell Nucleus; D002868:Chromosomal Proteins, Non-Histone; D015870:Gene Expression; D016679:Genome, Viral; D006367:HeLa Cells; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000378:metabolism*; D006570:Heterochromatin / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D009687:Nuclear Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012514:Sarcoma, Kaposi / Q000821:virology; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D000092468:Bromodomain Containing Proteins
D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D009687:Nuclear Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; C098415:BRD2 protein, human; D000092468:Bromodomain Containing Proteins; C490844:Brd2 protein, mouse; C118485:latent nuclear antigen (LNA)