A diagram of the genomes of EBV and KSHV/HHV8 and their expression pattern in EBV- and KSHV-associated AIDS lymphoma. (A) The EBV genome is shown in the same orientation as the KSHV genome. The terminal repeats of the 2 viral genomes are indicated by a pair of taller boxes at the end of the long unique coding region. EBV adopts its most restricted pattern of gene expression (latency pattern I) in BL and PEL cells; this involves expression of EBNA-1 from the Qp promoter, of the untranslated EBERs, and probably of a group of transcripts from the Bam A region. In some BL tumors, the use of an alternative latent EBV promoter, Wp, leads to the expression of EBNA-3A,B,C in the absence of EBNA-2 and LMP-1, resulting a significant protection against apoptosis of c-myc–expressing cells.79 In HL, EBV adopts latency pattern II, which involves expression of EBNA-1, the EBERs, and the 2 latent membrane proteins, LMP-1 and LMP-2A. LMP-2A is translated from a transcript that spans the terminal repeats in the circular viral episome found during latency. In DLBCL, EBV latency pattern III includes the expression of EBNA-2, EBNA-LP, EBNA-3A,B,C from the latent Wp promoter, as shown. Details on the function of EBNA-2, EBNA-LP, and EBNA-3A,B,C can be found in a recent review.61 (B) KSHV/HHV8 genome and viral genes expressed in PEL or MCD. The latent KSHV genes LANA, v-cyc, vFLIP, K12/kaposin, and vIRF-3/K10.5/LANA-2 are shown as black stippled boxes; the position of the KSHV miRNAs is indicated by vertical lines. These genes are expressed in the majority of tumor cells in vivo and in PEL cell lines. Viral genes expressed in only a subpopulation of PEL or MCD cells (eg, vIL6) are cross-hatched, and those expressed only during the later stages of the productive (lytic) viral replication cycle are stippled. The viral gene expression pattern in PEL is more restricted than in MCD. Whereas LANA, vcyc/vFLIP, the miRNAs, and vIRF-3/K10.5/LANA-2 are expressed in most, vIL6 is expressed only in a small proportion of lymphoma cells. Other lytic genes are only rarely expressed and are therefore not shown in this diagram for PEL. In MCD, several lytic KSHV genes are expressed in a few cells, suggesting noticeable productive viral replication in this condition.
