The structure and coding organization of the genomic termini of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8)

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is a novel human herpesvirus closely linked to two AIDS-related neoplasms. We have prepared DNA from KSHV virions produced in cell culture and have examined the structure of the viral genomic termini. As in the related simian herpesvirus H. saimiri (HVS), the central unique region of KSHV DNA is bounded by tandemly repeated units of noncoding, GC-rich DNA. The KSHV repeats are 803 bp in length and are 85% G+C. Each molecule harbors 35-45 such repeats, but the repeats are not arrayed uniformly and symmetrically at each end. Rather, different molecules appear to contain different numbers of repeats at each end, with the sum total of repeated DNA per genome being relatively fixed, since the full genome is uniformly 165-170 kb. Thus, molecules with many repeats at one end will have fewer at the other. Because the unique viral genes bordering the left-hand repeats of the HVS genome play key roles in oncogenesis, we also examined the coding organization of the corresponding region of KSHV. No homologs of the HVS transforming genes were identified in this region of KSHV; rather, this region bears a novel gene encoding a putative transmembrane protein that appears to be upregulated during the early phase of lytic viral replication.