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Philosophical Transactions of the Royal... Apr 2001Herpesvirus saimiri (saimiriine herpesvirus 2) is the classical prototype of the gamma(2)-herpesviruses or rhadinoviruses, which also contains a human member, the... (Review)
Review
Herpesvirus saimiri (saimiriine herpesvirus 2) is the classical prototype of the gamma(2)-herpesviruses or rhadinoviruses, which also contains a human member, the Kaposi's sarcoma-associated herpesvirus. The T-lymphotropic Herpesvirus saimiri establishes specific replicative and persistent conditions in different primate host species. Virtually all squirrel monkeys (Saimiri sciureus) are persistently infected with this virus. In its natural host, the virus does not cause disease, whereas it induces fatal acute T-cell lymphoma in other monkey species after experimental infection. The virus can be isolated by cocultivation of permissive epithelial cells with peripheral blood cells from naturally infected squirrel monkeys and from susceptible New World monkeys during the virus-induced disease. Tumour-derived and in vitro-transformed T-cell lines from New World monkeys release virus particles. Herpesvirus ateles is a closely related virus of spider monkeys (Ateles spp.) and has similar pathogenic properties to Herpesvirus saimiri in other New World primate species. Similar to other rhadinoviruses, the genome of Herpesvirus saimiri harbours a series of virus genes with pronounced homology to cellular counterparts including a D-type cyclin, a G-protein-coupled receptor, an interleukin-17, a superantigen homologue, and several inhibitors of the complement cascade and of different apoptosis pathways. Preserved function has been demonstrated for most of the homologues of cellular proteins. These viral functions are mostly dispensable for the transforming and pathogenic capability of the virus. However, they are considered relevant for the apathogenic persistence of Herpesvirus saimiri in its natural host. A terminal region of the non-repetitive coding part of the virus genome is essential for pathogenicity and T-cell transformation. Based on the pathogenic phenotypes and the different alleles of this variable region, the virus strains have been assigned to three subgroups, termed A, B and C. In the highly oncogenic subgroup C strains, the two virus genes stpC and tip are transcribed from one bicistronic mRNA and are essential for transformation and leukaemia induction. stpC fulfils the typical criteria of an oncogene; its product interacts with Ras and tumour necrosis factor-associated factors and induces mitogen-activated protein kinase and nuclear factor kappa B activation. Tip interacts with the RNA transport factor Tap, with signal transduction and activation of transcription factors, and with the T-cellular tyrosine kinase Lck, which is activated by this interaction and phosphorylates Tip as a substrate. It is of particular interest that certain subgroup C virus strains such as C488 are capable of transforming human T lymphocytes to stable growth in culture. The transformed human T cells harbour multiple copies of the viral genome in the form of stable, non-integrated episomes. The cells express only a few virus genes and do not produce virus particles. The transformed cells maintain the antigen specificity and many other essential functions of their parental T-cell clones. Based on the preserved functional phenotype of the transformed T cells, Herpesvirus saimiri provides useful tools for T-cell immunology, for gene transfer and possibly also for experimental adoptive immunotherapy.
Topics: Animals; Cell Transformation, Viral; Gene Transfer Techniques; Genes, Viral; Genetic Vectors; Genome, Viral; Herpesviridae Infections; Herpesvirus 2, Saimiriine; Humans; T-Lymphocytes; Tumor Virus Infections; Virus Replication
PubMed: 11313011
DOI: 10.1098/rstb.2000.0780 -
Molecular and Cellular Biology Nov 1994Herpesvirus saimiri contains an open reading frame called eclf2 with homology to the cellular type D cyclins. We now show that the eclf2 gene product is a novel...
Herpesvirus saimiri contains an open reading frame called eclf2 with homology to the cellular type D cyclins. We now show that the eclf2 gene product is a novel virus-encoded cyclin (v-cyclin). The protein encoded by the v-cyclin gene of this oncogenic herpesvirus was found to have an apparent molecular size of 29 kDa in transformed cells. v-Cyclin protein was found to be associated with cdk6, a cellular cyclin-dependent kinase known to interact with cellular type D cyclins. cdk6/v-cyclin complexes strongly phosphorylated Rb fusion protein and histone H1 as substrates in vitro. Mutational analyses showed that highly conserved amino acids in the cyclin box of v-cyclin were important for association with cdk6 and for activation of cdk6 kinase activity. Thus, v-cyclin resembles cellular type D cyclins in primary sequence, in its association with cdk6, by its ability to activate protein kinase activity, and by the presence of functional cyclin box sequences. v-Cyclin exhibited a selective preference for association with cdk6 over other cyclin-dependent kinases and a high level of kinase activation. The properties of v-cyclin suggest a likely role in oncogenic transformation by this T-lymphotropic herpesvirus.
Topics: Amino Acid Sequence; Animals; Base Sequence; Cell Cycle; Cell Line; Conserved Sequence; Cyclin-Dependent Kinase 6; Cyclin-Dependent Kinases; Cyclins; DNA Primers; DNA, Viral; Genes, Viral; Herpesvirus 2, Saimiriine; Molecular Sequence Data; Molecular Weight; Moths; Mutation; Open Reading Frames; Phosphorylation; Protein Kinases; Protein Serine-Threonine Kinases
PubMed: 7935438
DOI: 10.1128/mcb.14.11.7235-7244.1994 -
Viruses Jul 2022Herpesvirus saimiri (HVS) is discussed as a possible vector in gene therapy. In order to create a self-repairing HVS vector, the F plasmid vector moiety of the bacterial...
Herpesvirus saimiri (HVS) is discussed as a possible vector in gene therapy. In order to create a self-repairing HVS vector, the F plasmid vector moiety of the bacterial artificial chromosome (BAC) was transposed via Red recombination into the virus genes or , both important for virus replication. Repetitive sequences were additionally inserted, allowing the removal of the F-derived sequences from the viral DNA genome upon reconstitution in permissive epithelial cells. Moreover, these self-repair-enabled BACs were used to generate deletion variants of the transforming strain C488 in order to minimalize the virus genome. Using the mutagenesis with two subsequent homologous recombination steps, the BAC was seamlessly manipulated. To ensure the replication capacity in permissive monkey cells, replication kinetics for all generated virus variants were documented. HVS variants with increased insert capacity reached the self-repair within two to three passages in permissive epithelial cells. The seamless deletion of , , did not abolish replication competence. Apoptosis induction did not seem to be altered in human T cells transformed with deletion variants lacking or . These virus variants form an important step towards creating a potential minimal virus vector for gene therapy, for example, in human T cells.
Topics: Chromosomes, Artificial, Bacterial; Genes, Viral; Genetic Vectors; Genome, Viral; Herpesvirus 2, Saimiriine; Humans
PubMed: 35891505
DOI: 10.3390/v14071525 -
Veterinary Microbiology Jan 2010Herpesviruses are highly host specific and share a long synchronous evolution with their hosts. Only in rare cases, species barriers fall and allow animal to human or... (Review)
Review
Herpesviruses are highly host specific and share a long synchronous evolution with their hosts. Only in rare cases, species barriers fall and allow animal to human or human to animal transmission. Among the zoonotic herpesviruses, Cercopithecine herpesvirus 1 is the most significant and can be transmitted from macaques to human. Conversely, Human herpesvirus 1 is capable of causing severe disease in primates. Besides those two examples, there are several herpesviruses with a certainly limited or only suspected ability to cross species barriers. Those include Saimiriine herpesvirus 2, Phocid herpesvirus 2, Equid herpesvirus 1, Epstein-Barr Virus, Marek's disease virus, and Pseudorabies virus. Concerning xenotransplantations, porcine gammaherpesviruses must be considered as a zoonotic threat.
Topics: Animals; Herpesviridae; Herpesviridae Infections; Humans; Primates; Zoonoses
PubMed: 19616388
DOI: 10.1016/j.vetmic.2009.06.020 -
RNA Biology 2018Viruses masterfully regulate host gene expression during infection. Many do so, in part, by expressing non-coding RNAs. Recent work has shown that HSUR 2, a viral... (Review)
Review
Viruses masterfully regulate host gene expression during infection. Many do so, in part, by expressing non-coding RNAs. Recent work has shown that HSUR 2, a viral non-coding RNA expressed by the oncogenic Herpesvirus saimiri, regulates mRNA expression through a novel mechanism. HSUR 2 base pairs with both target mRNAs and host miRNAs in infected cells. This results in HSUR 2-dependent recruitment of host miRNAs and associated Ago proteins to target mRNAs, and the subsequent destabilization of target mRNAs. Using this mechanism, this virus regulates key cellular pathways during viral infection. Here I discuss the evolution of our thinking about HSUR function and explore the implications of recent findings in relation to the current views on the functions of interactions between miRNAs and other classes of non-coding RNAs, the potential advantages of this mechanism of regulation of gene expression, and the evolutionary origin of HSUR 2.
Topics: Argonaute Proteins; Base Sequence; Gene Expression Regulation, Viral; Herpesviridae Infections; Herpesvirus 2, Saimiriine; Host-Pathogen Interactions; Humans; RNA, Messenger; RNA, Untranslated; RNA, Viral
PubMed: 29895222
DOI: 10.1080/15476286.2018.1467176 -
Comparative Medicine Feb 2008With the emergence of the AIDS epidemic over the last 2 decades and the more recent identification of Kaposi sarcoma-associated herpesvirus (KSHV, Human herpesvirus 8),... (Review)
Review
With the emergence of the AIDS epidemic over the last 2 decades and the more recent identification of Kaposi sarcoma-associated herpesvirus (KSHV, Human herpesvirus 8), the genera of rhadinoviruses have gained importance as a family of viruses with oncogenic potential. First recognized in New World primates more than 30 y ago, the rhadinoviruses Saimiriine herpesvirus 2 and Ateline herpesvirus 2 have well-described transforming capabilities. Recently several new species-specific rhadinoviruses of Old World primates have been described, including retroperitoneal fibromatosis herpesvirus and rhesus rhadinovirus (Cercopithecine herpesvirus 17). Molecular analysis of these viruses has elucidated several functionally conserved genes and properties shared with KSHV involved in cellular proliferation, transformation, and immune evasion that facilitate the oncogenic potential of these viruses. This review examines the comparative pathobiology of KSHV, discusses the role of macaque rhadinoviruses as models of human disease, and outlines the derivation of specific pathogen-free animals.
Topics: Animals; Female; Herpes Simplex; Herpesvirus 1, Cercopithecine; Herpesvirus 2, Human; Herpesvirus 8, Human; Humans; Infectious Disease Transmission, Vertical; Interferon Regulatory Factor-1; Interferon Regulatory Factors; MicroRNAs; Open Reading Frames; Platyrrhini; Pregnancy; Primate Diseases; RNA, Viral; Sarcoma, Kaposi; Simplexvirus; Viral Proteins
PubMed: 19793454
DOI: No ID Found -
Molecules and Cells Aug 1999Gammaherpesviruses are the most rapidly growing members of the herpesviridae family. Gamma herpesviruses share similarity in their genome organizations and in early and... (Review)
Review
Gammaherpesviruses are the most rapidly growing members of the herpesviridae family. Gamma herpesviruses share similarity in their genome organizations and in early and late lytic genes that are required for viral replication. A distinct characteristic of gamma herpesviruses is their ability to establish latent infection in lymphoid cells, and some of these viruses are closely associated with abnormal proliferation and cancer in primates. The first open reading frame of the primate gamma herpesviruses has been shown to directly contribute to virus-associated pathogenesis. This open reading frame encodes latent membrane protein-1 (LMP1) in Epstein-Barr virus, Saimiri transformation protein (STP) in Herpesvirus Saimiri, K1 in Kaposi's sarcoma-associated herpesvirus, and R1 in Rhesus monkey Rhadinovirus. All of these gene products are capable of eliciting cellular signal transduction events, resulting in cell growth transformation. This review briefly summarizes the current view on the transforming mechanisms utilized by primate herpesviral oncogenes.
Topics: Animals; Cell Transformation, Neoplastic; Gammaherpesvirinae; Herpesvirus 8, Human; Macaca mulatta; Models, Genetic; Oncogene Proteins, Viral; Rhadinovirus; Signal Transduction; Viral Matrix Proteins; Viral Proteins
PubMed: 10515596
DOI: No ID Found -
Frontiers in Immunology 2018Herpesviruses have developed a variety of sophisticated immune evasion strategies to establish lifelong latent infection, including the use of long non-coding RNAs... (Review)
Review
Herpesviruses have developed a variety of sophisticated immune evasion strategies to establish lifelong latent infection, including the use of long non-coding RNAs (lncRNAs). In this review, we summarize the lncRNA action modes, i.e., RNA-protein, RNA-RNA, and RNA-DNA interactions, involved in regulating important aspects of immunity by controlling gene expression at various stages. Upon herpesvirus infection, host lncRNAs, such as nuclear paraspeckle assembly transcript 1, negative regulator of antiviral, and B-cell integration cluster have been functionally characterized as negative or positive antiviral regulators in the immune response. Herpesviruses have also evolved multiple strategies to modulate the host immune response using lncRNAs, such as latency-associated transcript, β 2.7 RNA, 5 kb and 7.2 kb lncRNAs, Epstein-Barr virus-encoded non-coding RNA, H I-A rightward transcripts, polyadenylated nuclear, and herpesvirus saimiri U-rich RNAs. We discuss the various mechanisms of immune-related lncRNAs, and their diversified and important functions in the modulation of innate and adaptive immunity upon herpesvirus infection as well as in host-pathogen interactions, which will facilitate our understanding of rational design of novel strategies to combat herpesvirus infection.
Topics: Animals; Gene Expression Regulation; Herpesviridae Infections; Host-Pathogen Interactions; Humans; Immune Evasion; RNA, Long Noncoding
PubMed: 29706968
DOI: 10.3389/fimmu.2018.00761 -
ERJ Open Research Jul 2020https://bit.ly/2ZrKiDJ.
https://bit.ly/2ZrKiDJ.
PubMed: 32832526
DOI: 10.1183/23120541.00243-2020 -
Cold Spring Harbor Symposia on... 2010Primate herpesviruses express more noncoding RNAs (ncRNAs) than any other class of mammalian viruses during either latency or the lytic phase of the viral life cycle. T... (Review)
Review
Primate herpesviruses express more noncoding RNAs (ncRNAs) than any other class of mammalian viruses during either latency or the lytic phase of the viral life cycle. T cells transformed by the monkey virus Herpesvirus saimiri (HVS) express seven viral U-rich ncRNAs called HSURs. Conserved sequences in HSURs1 and 2 exhibit complementarity to three host-cell microRNAs (miRNAs). The predicted interactions of HSURs1 and 2 with these miRNAs were confirmed by coimmuno-precipitation experiments performed on extracts of marmoset T cells transformed by a wild-type or a mutant HVS lacking these two HSURs. Mutational analyses demonstrated that the binding of miR-27 to HSUR1 and that of miR-16 to HSUR2 involves base pairing. One of these miRNAs, miR-27, is dramatically lowered in abundance in HVS-transformed cells, with consequent effects on the expression of miR-27 target genes. Transient knockdown and ectopic expression of HSUR1 demonstrated that degradation of mature miR-27 occurs in a sequence-specific and binding-dependent manner but does not occur by AU-rich element (ARE)-mediated decay, which controls the intracellular level of HSUR1 itself. This viral strategy exemplifies the use of an ncRNA to control host-cell gene expression via the miRNA pathway and has potential applications both experimentally and therapeutically.
Topics: Animals; Base Sequence; Down-Regulation; Herpesvirus 2, Saimiriine; Host-Pathogen Interactions; MicroRNAs; Molecular Sequence Data; RNA, Untranslated; RNA, Viral
PubMed: 21139068
DOI: 10.1101/sqb.2010.75.009