Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8)

Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8)

^*Columbia Genome Center, Columbia University College of Physicians and Surgeons, New York, NY 10032; ^§Department of Pathology, Columbia University College of Physicians and Surgeons, New York, NY 10032; and ^¶Division of Epidemiology, School of Public Health, Columbia University, New York, NY 10032

Abstract

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 flanked by multiple G+C-rich 801-bp terminal repeat sequences. A genomic duplication that apparently arose in the parental tumor is present in this cell culture-derived strain. At least 81 ORFs, including 66 with homology to herpesvirus saimiri ORFs, and 5 internal repeat regions are present in the long unique region. The virus encodes homologs to complement-binding proteins, three cytokines (two macrophage inflammatory proteins and interleukin 6), dihydrofolate reductase, bcl-2, interferon regulatory factors, interleukin 8 receptor, neural cell adhesion molecule-like adhesin, and a D-type cyclin, as well as viral structural and metabolic proteins. Terminal repeat analysis of virus DNA from a KS lesion suggests a monoclonal expansion of KSHV in the KS tumor.

Footnotes

↵ † J.J.R. and R.A.B. contributed equally to this work.
↵ ‡ To whom reprint requests should be addressed.
Isidore S. Edelman
Abbreviations: KS, Kaposi sarcoma; KSHV, KS-associated herpesvirus; HVS, herpesvirus saimiri; EBV, Epstein–Barr virus; LUR, long unique region; TR, terminal repeat; ORF, open reading frame; MIP, macrophage inflammatory peptide; IRF, interferon regulatory factor, IL, interleukin; IB, interblock region; R, receptor; V, viral.

Data deposition: The sequences reported in this paper have been deposited in the GenBank data base [accession nos. U75698U75698 (long unique unit) and U75699U75699 and U75700U75700 (terminal repeat unit)].