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Species specificity of macaque rhadinovirus glycoprotein B sequences.

ABSTRACT: All members of the Herpesviridae family contain sequences for a highly conserved glycoprotein B (gB) gene. We investigated the phylogenetic relationships of gB sequences from eight independent rhadinovirus isolates obtained from three species: rhesus (Macaca mulatta), cynomologus (Macaca fasicularis), and pig-tailed (Macaca nemestrina) macaques. Samples were derived from monkeys housed at four separate facilities. Analysis of these eight independent gB sequences revealed five regions of heterogeneity within the 823- to 829-amino-acid polypeptides: residues 1 to 65, 120 to 185, 255 to 300, 352 to 393, and 412 to 457. The remaining regions of gB were highly conserved among the different macaque isolates. Overall divergence among these gene sequences ranged from 0.1 to 7.2% at the amino acid level. Phylogenetic trees constructed with our macaque rhadinovirus gB sequences and those derived from additional subfamilies or genera (alpha, beta, gamma-1, and gamma-2) revealed that the macaque gB sequences branched with other gamma-2 herpesvirus gB sequences and that within the gamma-2 genera, the macaque gB sequences clustered as a distinct branch. The eight macaque rhadinovirus gB sequences were all approximately equidistant from Kaposi sarcoma-associated herpesvirus (KSHV) gB sequences and had a shorter evolutionary distance to KSHV gB sequences than to any other herpesvirus, including the gamma-2 herpesvirus saimiri (HVS) of New World squirrel monkeys. The macaque gB sequences did not cluster according to the facility of origin, but did cluster according to the species of origin, displaying less intraspecies divergence (0.1 to 2.9%) than interspecies divergence (3.3 to 7.2%). These results demonstrate a close relatedness of rhadinovirus isolates from different macaque species.

SUBMITTER: Auerbach MR

PROVIDER: S-EPMC111576 | biostudies-literature | 2000 Jan

REPOSITORIES: biostudies-literature

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Species specificity of macaque rhadinovirus glycoprotein B sequences.

Auerbach M R MR Czajak S C SC Johnson W E WE Desrosiers R C RC Alexander L L

Journal of virology 20000101 1

All members of the Herpesviridae family contain sequences for a highly conserved glycoprotein B (gB) gene. We investigated the phylogenetic relationships of gB sequences from eight independent rhadinovirus isolates obtained from three species: rhesus (Macaca mulatta), cynomologus (Macaca fasicularis), and pig-tailed (Macaca nemestrina) macaques. Samples were derived from monkeys housed at four separate facilities. Analysis of these eight independent gB sequences revealed five regions of heteroge ...[more]

PMID: 10590154

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Project description:UnlabelledTwo 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.ImportanceThis 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.

Project description:UnlabelledJapanese macaque (JM) rhadinovirus (JMRV) is a novel, gamma-2 herpesvirus that was recently isolated from JM with inflammatory demyelinating encephalomyelitis (JME). JME is a spontaneous and chronic disease with clinical characteristics and immunohistopathology comparable to those of multiple sclerosis in humans. Little is known about the molecular biology of JMRV. Here, we sought to identify and characterize the small RNAs expressed during lytic JMRV infection using deep sequencing. Fifteen novel viral microRNAs (miRNAs) were identified in JMRV-infected fibroblasts, all of which were readily detectable by 24 h postinfection and accumulated to high levels by 72 h. Sequence comparisons to human Kaposi's sarcoma-associated herpesvirus (KSHV) miRNAs revealed several viral miRNA homologs. To functionally characterize JMRV miRNAs, we screened for their effects on nuclear factor kappa B (NF-κB) signaling in the presence of two proinflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β). Multiple JMRV miRNAs suppressed cytokine-induced NF-κB activation. One of these miRNAs, miR-J8, has seed sequence homology to members of the cellular miR-17/20/106 and miR-373 families, which are key players in cell cycle regulation as well as inflammation. Using reporters, we show that miR-J8 can target 3' untranslated regions (UTRs) with miR-17-5p or miR-20a cognate sites. Our studies implicate JMRV miRNAs in the suppression of innate antiviral immune responses, which is an emerging feature of many viral miRNAs.ImportanceGammaherpesviruses are associated with multiple diseases linked to immunosuppression and inflammation, including AIDS-related cancers and autoimmune diseases. JMRV is a recently identified herpesvirus that has been linked to JME, an inflammatory demyelinating disease in Japanese macaques that mimics multiple sclerosis. There are few large-animal models for gammaherpesvirus-associated pathogenesis. Here, we provide the first experimental evidence of JMRV miRNAs in vitro and demonstrate that one of these viral miRNAs can mimic the activity of the cellular miR-17/20/106 family. Our work provides unique insight into the roles of viral miRNAs during rhadinovirus infection and provides an important step toward understanding viral miRNA function in a nonhuman primate model system.

Dataset Information

Species specificity of macaque rhadinovirus glycoprotein B sequences.

Publications

Species specificity of macaque rhadinovirus glycoprotein B sequences.

Similar Datasets

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