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Originally published as JGV in Press, 10.1099/vir.0.007971-0 on March 4, 2009 J Gen Virol 90 (2009), 1190-1201; DOI 10.1099/vir.0.007971-0

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Identification and functional characterization of a spliced rhesus rhadinovirus gene with homology to the K15 gene of Kaposi's sarcoma-associated herpesvirus

Linding Wang1,2,{dagger}, Marcel Pietrek1,{dagger}, Melanie M. Brinkmann1,{ddagger}, Anika Hävemeier1, Irina Fischer1, Bernd Hillenbrand1, Oliver Dittrich-Breiholz3, Michael Kracht4,§, Simon Chanas5, David J. Blackbourn5 and Thomas F. Schulz1

1 Institute of Virology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany
2 State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Science, Wuhan 430071, PR China
3 Institute of Biochemistry, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany
4 Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany
5 CRUK Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TT, UK

Correspondence
Thomas F. Schulz
Schulz.thomas{at}mh-hannover.de

Rhesus monkey rhadinovirus (RRV) is a gamma-2 herpesvirus related to the human Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8). This study identified an alternatively spliced gene at the right side of the RRV genome (strain 17577) between open reading frame 75 and the terminal repeat region. Of its eight exons, the first seven encoded up to 12 transmembrane domains, whilst the eighth exon encoded a predicted C-terminal cytoplasmic domain. Structurally and positionally, this RRV gene therefore resembles the K15 gene of KSHV; it was provisionally named RK15 to avoid confusion with other RRV17577 genes. In ectopic expression studies, the 55 kDa RK15 protein isoform activated the JNK and NF-{kappa}B pathways, like the 45 kDa KSHV K15-encoded protein isoform. In contrast to K15, which activates angiogenic and inflammatory cytokines such as interleukin (IL)-8, IL-6 and CCL20, the range of cellular transcripts activated by the RRV K15 homologue was much more restricted, but included IL-6, IL-8 and FGF21. These data suggest functional differences between terminal membrane proteins at the right end of the genomes of Old World primate gamma-2 herpesviruses.

{dagger}These authors contributed equally to this work.

{ddagger}Present address: Whitehead Institute for Biomedical Research, Cambridge, MA, USA.

§Present address: Rudolf-Buchheim-Institute of Pharmacology, Justus-Liebig-University Giessen, Frankfurter Strasse 107, D-35392 Giessen, Germany.







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