Identification and functional characterization of a spliced rhesus rhadinovirus gene with homology to the K15 gene of Kaposi's sarcoma-associated herpesvirus.
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-kappaB 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.
Wang
Linding
L
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Science, Wuhan 430071, PR China.|Institute of Virology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
Pietrek
Marcel
M
Institute of Virology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
Brinkmann
Melanie M
MM
Institute of Virology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
Hävemeier
Anika
A
Institute of Virology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
Fischer
Irina
I
Institute of Virology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
Hillenbrand
Bernd
B
Institute of Virology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
Dittrich-Breiholz
Oliver
O
Institute of Biochemistry, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
Kracht
Michael
M
Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
Chanas
Simon
S
CRUK Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TT, UK.
Blackbourn
David J
DJ
CRUK Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TT, UK.
Schulz
Thomas F
TF
Institute of Virology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D005814:Genes, Viral; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008253:Macaca mulatta; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D018144:Rhadinovirus / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D017385:Sequence Homology; D014158:Transcription, Genetic; D014764:Viral Proteins
D016328:NF-kappa B; D014764:Viral Proteins; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases