title: Complete genome sequence of Pig-tailed macaque rhadinovirus 2 and its evolutionary relationship with rhesus macaque rhadinovirus and human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus.
abstract: Two rhadinovirus lineages have been identified in Old World primates. The rhadinovirus 1 (RV1) lineage consists of human herpesvirus 8, Kaposi's sarcoma-associated herpesvirus (KSHV), and closely related rhadinoviruses of chimpanzees, gorillas, macaques and other Old World primates. The RV2 rhadinovirus lineage is distinct and consists of closely related viruses from the same Old World primate species. Rhesus macaque rhadinovirus (RRV) is the RV2 prototype, and two RRV isolates, 26-95 and 17577, were sequenced. We determined that the pig-tailed macaque RV2 rhadinovirus, MneRV2, is highly associated with lymphomas in macaques with simian AIDS. To further study the role of rhadinoviruses in the development of lymphoma, we sequenced the complete genome of MneRV2 and identified 87 protein coding genes and 17 candidate microRNAs (miRNAs). A strong genome colinearity and sequence homology were observed between MneRV2 and RRV26-95, although the open reading frame (ORF) encoding the KSHV ORFK15 homolog was disrupted in RRV26-95. Comparison with MneRV2 revealed several genomic anomalies in RRV17577 that were not present in other rhadinovirus genomes, including an N-terminal duplication in ORF4 and a recombinative exchange of more distantly related homologs of the ORF22/ORF47 interacting glycoprotein genes. The comparison with MneRV2 has revealed novel genes and important conservation of protein coding domains and transcription initiation, termination, and splicing signals, which have added to our knowledge of RV2 rhadinovirus genetics. Further comparisons with KSHV and other RV1 rhadinoviruses will provide important avenues for dissecting the biology, evolution, and pathology of these closely related tumor-inducing viruses in humans and other Old World primates.
  
  
  OBJECTIVE
  This work provides the sequence characterization of MneRV2, the pig-tailed macaque homolog of rhesus rhadinovirus (RRV). MneRV2 and RRV belong to the rhadinovirus 2 (RV2) rhadinovirus lineage of Old World primates and are distinct but related to Kaposi's sarcoma-associated herpesvirus (KSHV), the etiologic agent of Kaposi's sarcoma. Pig-tailed macaques provide important models of human disease, and our previous studies have indicated that MneRV2 plays a causal role in AIDS-related lymphomas in macaques. Delineation of the MneRV2 sequence has allowed a detailed characterization of the genome structure, and evolutionary comparisons with RRV and KSHV have identified conserved promoters, splice junctions, and novel genes. This comparison provides insight into RV2 rhadinovirus biology and sets the groundwork for more intensive next-generation (Next-Gen) transcript and genetic analysis of this class of tumor-inducing herpesvirus. This study supports the use of MneRV2 in pig-tailed macaques as an important model for studying rhadinovirus biology, transmission and pathology.
authors.affiliation: Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA.
authors.forename: A Gregory
authors.initials: AG
authors.lastname: Bruce
authors.affiliation: University of Washington, Seattle, Washington, USA.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Thouless
authors.affiliation: University of Birmingham, Birmingham, United Kingdom.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Haines
authors.affiliation: University of Birmingham, Birmingham, United Kingdom.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Pallen
authors.affiliation: Leibniz Institute for Experimental Virology, Henrich-Pette-Institute, University of Hamburg, Hamburg, Germany.
authors.forename: Adam
authors.initials: A
authors.lastname: Grundhoff
authors.affiliation: Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA University of Washington, Seattle, Washington, USA timothy.rose@seattlechildrens.org.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Rose
mesh_terms: D000818:Animals; D004279:DNA, Viral / Q000737:chemistry* / Q000235:genetics*; D016679:Genome, Viral; D019288:Herpesvirus 8, Human / Q000235:genetics*; D008254:Macaca nemestrina / Q000821:virology; D035683:MicroRNAs / Q000235:genetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D018144:Rhadinovirus / Q000235:genetics* / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D026801:Synteny; D014764:Viral Proteins / Q000235:genetics
chemical_list: D004279:DNA, Viral; D035683:MicroRNAs; D014764:Viral Proteins