Changes in viral and cellular gene expression mediated by KSHV PAN lncRNA

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PROJECT SUMMARY Kaposi's sarcoma associated herpesvirus or human herpesvirus 8 (KSHV/HHV8) is a gamma herpesvirus that is the cause of Kaposi's sarcoma and body cavity lymphomas. During lytic reactivation, KSHV produces a highly abundant nuclear localized transcript, polyadenylated nuclear RNA, PAN RNA. PAN RNA was shown to regulate viral and cellular gene expression. One mechanism used by PAN RNA involves the mediation of changes in epigenetic modifications. A recombinant BACmid defective for PAN RNA expression fails to reactivate and produce supernatant virus. This established PAN RNA as an essential long non-coding RNA (lncRNA) for virus replication and growth. lncRNAs are defined as non protein coding transcripts longer than 200 bases. In mammalian cells lncRNAs are very abundant with numbers estimated in the tens of thousands and many are associated with disease. Many lncRNAs have now been characterized and have a broad range of functions. Many act to regulate transcription through a variety of mechanisms. lncRNAs can act as regulators of transcription by directly interacting with transcription factors as well as recruiting transcription complexes to specific promoters. For herpesviruses, several lncRNAs have now been identified including KSHV PAN RNA, human cytomegalovirus (HCMV) lncRNA4.9 and herpes simplex virus (HSV-1) LATs. However the full understanding of the role of herpesvirus encoded lncRNAs in infection is in its infancy. There is a critical need to define the function of herpesvirus lncRNAs and their contribution to virus replication and affects on cell gene expression.