Kaposi's sarcoma-associated herpesvirus (KSHV) also called human herpesvirus type 8 (HHV-8), is the likely etiological agent of Kaposi's sarcoma (KS) and two lymphoproliferative diseases: primary effusion lymphomas and multicentric Castleman's disease. Common to these malignancies is that tumor cells are latently infected with KSHV. Viral gene expression is limited to only a few genes one of which is the latency-associated nuclear antigen (LANA) a polypeptide of 1162 aa encoded by ORF73. Examination of the primary sequence of LANA reveals structural features reminiscent of transcription factors. We therefore tested whether LANA augments transcription by transient transfection assays and found that ORF73 can function as activator and repressor of transcription. Furthermore, preliminary data obtained by cDNA array-based expression profiling demonstrate changes of cellular gene expression in the presence of LANA. We hypothesize that LANA regulates cellular and viral transcription in latently infected cells and that these changes in host cellular gene expression are important for viral latency, persistence and possibly for viral transformation. We propose to study the effects of LANA in inducible cell lines by using oligonucleotide microarrays. This approach, together with experiments designed to elucidate the mechanism by which LANA functions, will add to a better understanding of KSHV pathogenesis.
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