Mattsson K, Kiss C, Platt GM, Simpson GR, Kashuba E, Klein G, Schulz TF, and Szekely L.
Microbiology and Tumor Biology Center, Karolinska Institute, PO Box
280, S-171 77, Stockholm, Sweden Department of Virology, Hannover Medical
School, D-30623 Hannover, Germany
Molecular Virology Group, Department of Medical Microbiology, The
University of Liverpool, Liverpool, UK.
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.
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