NUCLEOTIDE-SEQUENCE OF THE KAPOSI SARCOMA-ASSOCIATED HERPESVIRUS (HHV8)

The genome of the Kaposi sarcoma-associated herpesvirus (KSHV or HHV8) was mapped with cosmid and phage genomic libraries from the BC-1 cell line, Its nucleotide sequence was determined except for a 3-kb region at the right end of the genome that was refractory to cloning, The BC -1 KSHV genome consists of a 140.5-kb-long unique coding region flanke d by multiple G+C-rich 801-bp terminal repeat sequences, A genomic dup lication that apparently arose in the parental tumor is present in thi s cell culture-derived strain. At least 81 ORFs, including 66 with hom ology to herpesvirus saimiri ORFs, and 5 internal repent regions are p resent in the long unique region, The virus encodes homologs to comple ment-binding proteins, threecytokines (two macrophage inflammatory pro teins and interleukin 6), dihydrofolate reductase, bcl-2, interferon r egulatory factors, interleukin 8 receptor, neural cell adhesion molecu lelike adhesin, and a D-type cyclin, as well as viral structural and m etabolic proteins, Terminal repeat analysis of virus DNA from a KS les ion suggests a monoclonal expansion of KSHV in the KS tumor.