| distinct roles of cellular lck and p80 proteins in herpesvirus saimiri tip function on lipid rafts. | lipid rafts are proposed to function as platforms for both receptor signaling and trafficking. following interaction with antigenic peptides, the t-cell receptor (tcr) rapidly translocates to lipid rafts, where it transmits signals and subsequently undergoes endocytosis. the tip protein of herpesvirus saimiri (hvs), which is a t-lymphotropic tumor virus, interacts with cellular lck tyrosine kinase and p80, a wd domain-containing endosomal protein. interaction of tip with p80 induces enlarged ves ... | 2003 | 12885920 |
| activation of mitogen-activated protein kinase and nf-kappab pathways by a kaposi's sarcoma-associated herpesvirus k15 membrane protein. | the k15 gene of kaposi's sarcoma-associated herpesvirus (also known as human herpesvirus 8) consists of eight alternatively spliced exons and has been predicted to encode membrane proteins with a variable number of transmembrane regions and a common c-terminal cytoplasmic domain with putative binding sites for sh2 and sh3 domains, as well as for tumor necrosis factor receptor-associated factors. these features are reminiscent of the latent membrane proteins lmp-1 and lmp2a of epstein-barr virus ... | 2003 | 12915550 |
| the gammaherpesvirus 68 latency-associated nuclear antigen homolog is critical for the establishment of splenic latency. | open reading frame 73 (orf 73) is conserved among the gamma-2-herpesviruses (rhadinoviruses) and, in kaposi's sarcoma-associated herpesvirus (kshv) and herpesvirus saimiri (hvs), has been shown to encode a latency-associated nuclear antigen (lana). the kshv and hvs lanas have also been shown to be required for maintenance of the viral genome as an episome during latency. lana binds both the viral latency-associated origin of replication and the host cell chromosome, thereby ensuring efficient pa ... | 2003 | 12970414 |
| the genome of herpesvirus saimiri c488 which is capable of transforming human t cells. | herpesvirus saimiri (hvs), the rhadinovirus prototype, is apathogenic in the persistently infected natural host, the squirrel monkey, but causes acute t cell leukemia in other new world primate species. in contrast to subgroups a and b, only strains of hvs subgroup c such as c488 are capable of transforming primary human t cells to stable antigen-independent growth in culture. here, we report the complete 155-kb genome sequence of the transformation-competent hvs strain c488. the a+t-rich unique ... | 2003 | 14554077 |
| orf73 of herpesvirus saimiri strain c488 tethers the viral genome to metaphase chromosomes and binds to cis-acting dna sequences in the terminal repeats. | kaposi's sarcoma (ks)-associated herpesvirus (kshv), a human oncogenic gamma-2-herpesvirus, transforms human endothelial cells and establishes latent infection at a low efficiency in vitro. during latent infection, only a limited number of genes are expressed, and the circularized viral genome is maintained as a multicopy episome. latency-associated nuclear antigen (lana), exclusively expressed during latency, has been shown to have a multifunctional role in ks pathogenesis. lana tethers the vir ... | 2003 | 14610173 |
| generation and precise modification of a herpesvirus saimiri bacterial artificial chromosome demonstrates that the terminal repeats are required for both virus production and episomal persistence. | herpesvirus saimiri (hvs) is the prototype gamma-2 herpesvirus, and shares considerable homology with the human gammaherpesviruses kaposi's sarcoma-associated herpesvirus and epstein-barr virus. the generation of herpesvirus mutants is a key facet in the study of virus biology. the use of f-factor-based bacterial artificial chromosomes (bacs) to clone and modify the genomes of herpesviruses has enhanced the variety, precision and simplicity of mutant production. here we describe the cloning of t ... | 2003 | 14645920 |
| orf73 of murine herpesvirus-68 is critical for the establishment and maintenance of latency. | in vitro studies have established that the latency-associated nuclear antigen encoded by human kaposi's sarcoma-associated herpesvirus and the related orf73 gene product of herpesvirus saimiri interact with virus origins of replication to facilitate maintenance of episomal dna. such a function implies a critical role for orf73 in the establishment and maintenance of latency in vivo. to determine the role of orf73 in virus pathogenesis, the orf73 gene product encoded by murine herpesvirus-68 (mhv ... | 2003 | 14645921 |
| the herpesvirus saimiri orf73 gene product interacts with host-cell mitotic chromosomes and self-associates via its c terminus. | the herpesvirus saimiri (hvs) orf73 gene product shares limited homology with the orf73 protein of kaposi's sarcoma-associated herpesvirus (kshv). orf73 is expressed in an in vitro model of hvs latency, where the genome persists as a non-integrated circular episome. this suggests it may have a similar role to kshv orf73 in episomal maintenance, by tethering viral genomes to host-cell chromosomes. here, the association of orf73 with host mitotic chromosomes is described. deletion analysis demonst ... | 2004 | 14718629 |
| molecular mechanisms of the effect of herpesvirus saimiri protein stpc on the signaling pathway leading to nf-kappab activation. | herpesvirus saimiri (saimiriine herpesvirus-2) causes lethal t lymphoproliferative diseases in the susceptible species and transforms t lymphocytes to continuous growth in vitro. h. saimiri-induced transformation of t cells is becoming an important experimental tool of biomedical research. two proteins of h. saimiri subgroup c, tip and stpc, are essential for t cell transformation by this virus. it has been shown previously that stpc transforms fibroblasts, activates nf-kappab, and binds to tumo ... | 2004 | 14724292 |
| activation of bovine herpesvirus 4 lytic replication in a non-permissive cell line by overexpression of bohv-4 immediate early (ie) 2 gene. | bovine herpesvirus 4 (bohv-4) is a gammaherpesvirus with no clear disease association, it establishes persistent infections in its natural host, the bovine, and in an experimental host, the rabbit. bohv-4 immediate early 2 (ie2) rna is the less abundant, spliced, 1.8 kb rna. the predicted amino acid sequence, of the ie2 protein, reveals that it could encode a 61 kda protein with amino acid sequence homology to the epstein-barr virus (ebv) transactivator r protein and its homologues including, he ... | 2004 | 14738989 |
| tip, an lck-interacting protein of herpesvirus saimiri, causes fas- and lck-dependent apoptosis of t lymphocytes. | saimiriine herpesvirus-2 (herpesvirus saimiri) transforms t lymphocytes, including human, to continuous growth in vitro. h. saimiri-induced transformation is becoming an important tool of t-cell biology, including studies of hiv replication. two proteins of h. saimiri subgroup c, tip and stpc, are essential for t-cell transformation. in spite of the important role of these proteins, their biological functions and the molecular mechanisms of their action remain insufficiently understood. to furth ... | 2004 | 15016553 |
| activation of stat transcription factors by herpesvirus saimiri tip-484 requires p56lck. | signal transducers and activators of transcription (stats) relay signals from activated cell surface receptors directly to the nucleus. previously, a protein required for t-cell transformation by the dna tumor virus herpesvirus saimiri (hvs) and designated tyrosine kinase interacting protein (tip-484) was shown to interact with and dramatically upregulate the activity of p56lck. p56lck is a nonreceptor tyrosine kinase that is essential for signaling by the t-cell receptor and also interacts with ... | 1997 | 9261390 |
| efficient lentiviral transduction of herpesvirus saimiri immortalized t cells as a model for gene therapy in primary immunodeficiencies. | infection of human t lymphocytes with the herpesvirus saimiri (hvs) yields immortalized t-cell lines (hvs-t) which retain all the phenotypical and functional characteristics of their parental cells. this represents a new experimental model for studying genetic disorders of t lymphocytes. in spite of the efforts of many laboratories, no satisfactory way has been found so far to modify hvs-t cells genetically. we have analyzed the capacity of oncoretroviral (mlv)- and lentiviral (hiv-1)-based vect ... | 2004 | 15029233 |
| transcriptional activation of gammaherpesviral oncogene promoters by the hepatitis b viral x protein (hbx). | the latent membrane protein-1 (lmp1) of epstein-barr virus (ebv), saimiri transformation protein (stp) of herpesvirus saimiri (hvs), and k1 protein of kaposi's sarcoma-associated herpesvirus (kshv) are potent gammaherpesvirus oncogenes. to study the possible effects of double viral infection, we investigated the effects of oncogenic early proteins of dna viruses e1a and e1b (adenovirus-5), e6 and e7 (human papillomavirus-16), hbx (hepatitis b virus), tag (sv40), and gammaherpesviral oncogene dur ... | 2004 | 15068583 |
| apoptosis of bystander t cells induced by human immunodeficiency virus type 1 with increased envelope/receptor affinity and coreceptor binding site exposure. | apoptosis of uninfected bystander cd4(+) t cells contributes to t-cell depletion during human immunodeficiency virus type 1 (hiv-1) pathogenesis. the viral and host mechanisms that lead to bystander apoptosis are not well understood. to investigate properties of the viral envelope glycoproteins (env proteins) that influence the ability of hiv-1 to induce bystander apoptosis, we used molecularly cloned viruses that differ only in specific amino acids in env. the ability of these strains to induce ... | 2004 | 15078935 |
| the herpesvirus saimiri open reading frame (orf) 50 (rta) protein contains an at hook required for binding to the orf 50 response element in delayed-early promoters. | the herpesvirus saimiri open reading frame (orf) 50 encodes two proteins, which activate transcription directly, following interactions with delayed-early (de) promoters containing a specific motif. in this report, we demonstrate that orf 50 contains a dna binding domain that has homology to an at hook dna binding motif. deletion analysis of this domain reduces orf 50-mediated transactivation of the de orf 6 and orf 57 promoters by 100 and 90%, respectively. furthermore, gel retardation experime ... | 2004 | 15078979 |
| development of herpesvirus-based episomally maintained gene delivery vectors. | successful gene therapy aims to deliver and express therapeutic genes to cure or slow the progression of disease. however, a major obstacle in the application of gene therapy has been the development of the vectors used to deliver heterologous dna to the cell or tissue of choice. a number of viral- and non-viral-based vector systems have undergone clinical trials with varying success. however, at present, no vector system possesses the full complement of properties that are generally believed ne ... | 2004 | 15102599 |
| the herpesvirus saimiri small nuclear rnas recruit au-rich element-binding proteins but do not alter host au-rich element-containing mrna levels in virally transformed t cells. | herpesvirus saimiri (hvs) encodes seven sm-class small nuclear rnas, called hsurs (for herpesvirus saimiri u rnas), that are abundantly expressed in hvs-transformed, latently infected marmoset t cells but are of unknown function. hsurs 1, 2, and 5 have highly conserved 5'-end sequences containing the auuua pentamer characteristic of au-rich elements (ares) that regulate the stability of many host mrnas, including those encoding most proto-oncogenes and cytokines. to test whether the are-containi ... | 2004 | 15121869 |
| the cxc chemokine receptor encoded by herpesvirus saimiri, ecrf3, shows ligand-regulated signaling through gi, gq, and g12/13 proteins but constitutive signaling only through gi and g12/13 proteins. | open reading frame 74 (orf74) of many gamma(2)-herpesviruses encodes a cxc chemokine receptor. the molecular pharmacological profile of orf74 from herpesvirus saimiri, ecrf3, is characterized here and compared with that of the well known orf74 from human herpesvirus 8 (hhv8). the ecrf3 receptor bound the so-called elr (glu-leu-arg) cxc chemokines (125)i-cxcl1/gro alpha, (125)i-cxcl6/gcp-2, and (125)i-cxcl8/interleukin-8 with high affinity; but in contrast to orf74 from hhv8, it did not bind the ... | 2004 | 15155729 |
| activation of stat3 transcription factor by herpesvirus saimiri stp-a oncoprotein. | the saimiri transforming protein (stp) oncogene of herpesvirus saimiri subgroup a strain 11 (stp-a11) is not required for viral replication but is required for lymphoid cell immortalization in culture and lymphoma induction in primates. we previously showed that stp-a11 interacts with cellular src kinase through its sh2 binding motif and that this interaction elicits src signal transduction. here we demonstrate that stp-a11 interacts with signal transducer and activator of transcription 3 (stat3 ... | 2004 | 15163742 |
| modulation of t-cell receptor signal transduction by herpesvirus signaling adaptor protein. | because of its central regulatory role, t-cell receptor (tcr) signal transduction is a common target of viruses. we report here the identification of a small signaling protein, orf5, of the t-lymphotropic tumor virus herpesvirus saimiri (hvs). orf5 is predicted to contain 89 to 91 amino acids with an amino-terminal myristoylation site and six sh2 binding motifs, showing structural similarity to cellular lat (linker for activation of t cells). sequence analysis showed that, despite extensive sequ ... | 2004 | 15169900 |
| the t-cell lymphokine interleukin-26 targets epithelial cells through the interleukin-20 receptor 1 and interleukin-10 receptor 2 chains. | the cellular members of the interleukin-10 (il-10) cytokine family share sequence homology with il-10, whereas their sites of expression and their functions are divergent. one of these factors, ak155 or il-26, was discovered because of its overexpression in human t lymphocytes after growth transformation by the simian rhadinovirus herpesvirus saimiri. in addition, the gene is transcribed in various types of primary and immortalized t-cells. here we describe epithelial cells, namely colon carcino ... | 2004 | 15178681 |
| herpesvirus saimiri-encoded proteins tip and stpc modulate human immunodeficiency virus type 1 replication in t-cell lines and lymphocytes independently of viral tropism. | herpesvirus saimiri (hvs)-transformed t-lymphocytes are permissive for both x4 and r5 strains of human immunodeficiency virus type 1 (hiv-1). hvs-encoded proteins tyrosine-kinase interacting protein (tip) and saimiri transformation-associated protein subgroup c (stpc) were previously implicated in altering hiv permissiveness. molt4 cells expressing stpc or stpc and tip are permissive for x4 strains of hiv-1. in contrast, hiv-1 was restricted in molt4 cells expressing tip alone. here we show that ... | 2004 | 15183053 |
| dominant clones in immortalized t-cell lines from rheumatoid arthritis synovial membranes. | transformation of human t cells by herpesvirus saimiri allows the production of an unlimited number of t cells which express a functional t-cell receptor. in this study we transformed four t-cell lines derived from rheumatoid arthritis synovial membranes. the transformed t cells were mainly cd4+ and expressed the phenotype of activated t cells. they were grown for more than 1 year in the absence of mitogen or feeder cells, and three of them could be maintained without exogenous il-2. the presenc ... | 1997 | 9174133 |
| functional expression of thymidine kinase in human leukaemic and colorectal cells, delivered as egfp fusion protein by herpesvirus saimiri-based vector. | herpesvirus saimiri (hvs) has the capacity to incorporate large amounts of heterologous dna and can infect many different human cell types. to develop its potential as a gene therapy vector, we cloned herpes simplex virus thymidine kinase (tk) gene into the hvs genome in the form of an enhanced green fluorescent protein (egfp) fusion protein, using a cosmid-based approach. at multiplicity of infection = 100 over 90% of human leukemic k562 and jurkat cells were transduced with hvs/egfp-tk. condit ... | 2004 | 15243631 |
| characterization of the herpesvirus saimiri orf51 protein. | herpesvirus saimiri (hvs) is a gamma(2)-herpesvirus sharing genomic colinearity and a high degree of functional homology with hhv-8. to begin exploring the correlates of hvs infectivity and neutralization, we designed and implemented a new reporter assay. using this assay, we could demonstrate that hvs neutralizing antibodies are present at high levels in naturally infected squirrel monkeys and are strongly induced after pathogenic, experimental infection of common marmosets. further, we demonst ... | 2004 | 15262496 |
| herpesvirus ateles tio can replace herpesvirus saimiri stpc and tip oncoproteins in growth transformation of monkey and human t cells. | herpesvirus saimiri group c strains are capable of transforming human and simian t-lymphocyte populations to permanent antigen-independent growth. two viral oncoproteins, stpc and tip, that are encoded by a single bicistronic mrna, act in concert to mediate this phenotype. a closely related new world monkey herpesvirus, herpesvirus ateles, transcribes a single spliced mrna at an equivalent genome locus. the encoded protein, tio, has sequence homologies to both stpc and tip. we inserted the tio s ... | 2004 | 15331715 |
| inhibition of t cell receptor signal transduction by tyrosine kinase-interacting protein of herpesvirus saimiri. | t cells play a central role in orchestrating immunity against pathogens, particularly viruses. thus, impairing t cell activation is an important strategy employed by viruses to escape host immune control. the tyrosine kinase-interacting protein (tip) of the t lymphotropic herpesvirus saimiri (hvs) is constitutively present in lipid rafts and interacts with cellular lck tyrosine kinase and p80 endosomal protein. here we demonstrate that, due to the sequestration of lck by hvs tip, t cell receptor ... | 2004 | 15337788 |
| derivation of herpesvirus saimiri-transformed cd8+ t cell lines with noncytotoxic anti-hiv activity. | herpesvirus saimiri (hvs), strain 488-77, was used to derive continuously growing transformed human cd8+ t cell lines that can suppress hiv replication in cd4+ cells via the production of an antiviral factor(s). transformed cd8+ cell lines were obtained by hvs infection of peripheral blood mononuclear cells or purified cd8- t cells from hiv-infected or uninfected individuals. suppression of primary or laboratory isolates of hiv was mediated by factor permeation of a transwell membrane or by cell ... | 1997 | 9073551 |
| delta-9 tetrahydrocannabinol (thc) inhibits lytic replication of gamma oncogenic herpesviruses in vitro. | the major psychoactive cannabinoid compound of marijuana, delta-9 tetrahydrocannabinol (thc), has been shown to modulate immune responses and lymphocyte function. after primary infection the viral dna genome of gamma herpesviruses persists in lymphoid cell nuclei in a latent episomal circular form. in response to extracellular signals, the latent virus can be activated, which leads to production of infectious virus progeny. therefore, we evaluated the potential effects of thc on gamma herpesviru ... | 2004 | 15369590 |
| autocrine stimulation of rhadinovirus-transformed t cells by the chemokine ccl1/i-309. | the rhadinovirus herpesvirus saimiri transforms human t lymphocytes to stable growth in culture. besides the viral oncogenes stpc and tip, little is understood about the transformation process at the cellular level. to identify cellular factors that might contribute to growth transformation, we compared cellular gene expression in pairs of herpesvirus saimiri-transformed and nontransformed human t-cell clones. using cdna arrays and suppressive subtractive hybridization, we were able to identify ... | 2004 | 15378023 |
| cell transformation by herpesvirus saimiri. | herpesvirus saimiri (saimiriine herpesvirus-2), a gamma2-herpesvirus (rhadinovirus) of non-human primates, causes t-lymphoproliferative diseases in susceptible organisms and transforms human and non-human t lymphocytes to continuous growth in vitro in the absence of stimulation. t cells transformed by h. saimiri retain many characteristics of intact t lymphocytes, such as the sensitivity to interleukin-2 and the ability to recognize the corresponding antigens. as a result, h. saimiri is widely u ... | 2005 | 15389624 |
| functional phenotype of transformed human alphabeta and gammadelta t cells determined by different subgroup c strains of herpesvirus saimiri. | based on sequence divergence in the transformation-relevant region, herpesvirus saimiri strains are classified into three subgroups. only members of subgroup c transform human t lymphocytes to continuous interleukin-2-dependent growth in culture. in this study, human cord blood t cells were immortalized by using different subgroup c strains (c488, c484, and c139). the resulting t-cell lines represented different types of t-cell clones. they were either cd4+ or cd8+ and expressed either the alpha ... | 1997 | 9032360 |
| the prototype gamma-2 herpesvirus nucleocytoplasmic shuttling protein, orf 57, transports viral rna through the cellular mrna export pathway. | hvs (herpesvirus saimiri) is the prototype gamma-2 herpesvirus. this is a subfamily of herpesviruses gaining importance since the identification of the first human gamma-2 herpesvirus, kaposi's sarcoma-associated herpesvirus. the hvs orf 57 (open reading frame 57) protein is a multifunctional transregulatory protein homologous with genes identified in all classes of herpesviruses. recent work has demonstrated that orf 57 has the ability to bind viral rna, shuttles between the nucleus and cytopla ... | 2005 | 15537388 |
| efficient infection and persistence of a herpesvirus saimiri-based gene delivery vector into human tumor xenografts and multicellular spheroid cultures. | herpesvirus saimiri (hvs) has the ability to infect a variety of human cell lines and establish a persistent infection by virtue of episomal maintenance. moreover, the viral episome provides sustained expression of a heterologous transgene. hvs-based vectors can also persist for a long term in tumor xenografts generated from hvs-infected human carcinoma cell lines. the viral episome remains latent within the xenograft allowing long-term transgene expression. these properties, in addition to its ... | 2005 | 15540115 |
| characterization of lck-binding elements in the herpesviral regulatory tip protein. | herpesvirus saimiri encodes a tyrosine kinase interacting protein (tip) that binds to t-cell-specific tyrosine kinase lck via multiple sequence motifs and controls its activity. the regulation of lck by tip represents a key mechanism in the transformation of human t-lymphocytes during herpesviral infection. in this study, the interaction of tip with the regulatory sh3 and sh2 domains of lck was investigated by biophysical and computational techniques. nmr spectroscopy of isotopically labeled tip ... | 2004 | 15554700 |
| herpesvirus saimiri tip-484 membrane protein markedly increases p56lck activity in t cells. | herpesvirus saimiri (hvs) is a t-cell-specific transforming and oncogenic virus. a protein encoded by hvs known as tip-484 (for tyrosine kinase interacting protein from hvs strain 484) is required for this transformation. tip-484 binds specifically to the nonreceptor protein tyrosine kinase p56lck. by transfecting tip-484 into t cells, we now show that this interaction leads to a several hundred-fold increase in the kinase activity of p56lck. tip-484 is part of a protein complex which is depende ... | 1997 | 8985360 |
| lymphotropic herpesvirus saimiri uses the smn complex to assemble sm cores on its small rnas. | the lymphotropic herpesvirus saimiri (hvs) causes acute leukemia, t-cell lymphoma, and death in new world monkeys. hvs encodes seven small rnas (hsurs) of unknown function. the hsurs acquire host sm proteins and assemble sm cores similar to those found on the spliceosomal small nuclear rnps (snrnps). here we show that, like host snrnps, hsurs use the smn (survival of motor neurons) complex to assemble sm cores. the hsurs bind the smn complex directly and with very high affinity, similar to or hi ... | 2005 | 15632062 |
| regulated and constitutive expression of anti-inflammatory cytokines by nontransforming herpesvirus saimiri vectors. | herpesviral saimiri-(hvs) mediated expression of bovine growth hormone was one of the first applications of an episomal viral vector for gene therapy. meanwhile, the long-term persistence of hvs vectors has been confirmed in a broad spectrum of infectable target cells in vitro and in vivo. regulated gene expression is useful for many applications of gene therapy. therefore, we inserted the mifepristone-antiprogestin-inducible expression system (geneswitchtrade mark) into hvs viral vectors to reg ... | 2005 | 15647772 |
| herpesvirus saimiri immortalization of aotus t lymphocytes specific for an immunogenically modified peptide of plasmodium falciparum merozoite surface antigen 2. | the plasmodium merozoite surface antigen 2 (msa2) is one of several candidates for a protective vaccine against malaria. previous studies have shown that antibodies directed against the msa2 variable region are not protective and that constant regions are non-immunogenic. however, modified peptides derived from constant regions can be rendered immunogenic and partially protective in aotus monkeys. in this study, we reveal the establishment, using in vitro herpesvirus samiri (hvs) infection, of a ... | 2005 | 15661043 |
| the herpesvirus saimiri rta gene autostimulates via binding to a non-consensus response element. | herpesvirus saimiri orf 50a protein expression is sufficient to reactivate the entire lytic-replication cycle. orf 50a functions as a sequence-specific transactivator that is capable of activating delayed-early gene expression via direct binding to an orf 50 response element (re) within the respective promoter. here, it is shown that orf 50a is capable of transactivating its own promoter. deletion analysis of the orf 50a promoter showed that the orf 50-responsive element is contained within an 8 ... | 2005 | 15722517 |
| herpesvirus saimiri-transformed cd8+ t cells as a tool to study chediak-higashi syndrome cytolytic lymphocytes. | cytolytic cd8+ t lymphocytes are the main cell type involved in the fatal lymphoproliferative-accelerated phase of the chediak-higashi syndrome (chs). to generate a cellular tool to study the defects of this t cell subset in vitro, we have used herpesvirus saimiri, a lymphotropic virus that transforms human t lymphocytes into extended growth and in addition, endows them with natural killer (nk) features. transformed chs cd8+ t cells were generated and characterized in comparison with healthy con ... | 2005 | 15728247 |
| higher proliferative capacity of t lymphocytes from patients with crohn disease than from ulcerative colitis is disclosed by use of herpesvirus saimiri-transformed t-cell lines. | t lymphocytes play a crucial role in the pathogenesis of inflammatory bowel disease. achieving stable t-cell lines, rather than continuous bleeding of patients, is desirable in order to dissect their implication in the disease. | 2004 | 15743001 |
| lentiviral vectors transcriptionally targeted to hematopoietic cells by wasp gene proximal promoter sequences. | the development of vectors that express a therapeutic transgene efficiently and specifically in hematopoietic cells (hcs) is an important goal for gene therapy of hematological disorders. in order to achieve this, we used a 500 bp fragment from the proximal wasp gene promoter to drive the expression of the wasp cdna in the context of a self-inactivating lentiviral vector. single-round transduction of wasp-deficient herpesvirus saimiri (hvs)-immortalized cells as well as primary allospecific t ce ... | 2005 | 15750617 |
| t-cell transformation and oncogenesis by gamma2-herpesviruses. | gamma2-herpesviruses, also termed rhadinoviruses, have long been known as animal pathogens causing lymphoproliferative diseases such as malignant catarrhal fever in cattle or t-cell lymphoma in certain neotropical primates. the rhadinovirus prototype is herpesvirus saimiri (hvs), a t-lymphotropic agent of squirrel monkeys (saimiri sciureus); herpesvirus ateles (hva) is closely related to hvs. the first human rhadinovirus, human herpesvirus type 8 (hhv-8), was discovered a decade ago in kaposi's ... | 2005 | 15797445 |
| inactivation of herpes simplex virus by thiosemicarbazones and certain cations. | we demonstrated that herpes simplex virus types 1 and 2, including a type 2 strain which transforms hamster cells in vitro, and herpesvirus saimiri are inactivated by exposure to thiosemicarbazones. because thiosemicarbazones are thought to interact with heavy metals in this inactivation process (9), we tested and found some of these herpesviruses to be susceptible to exposure to certain heavy metals. a virion polymerase was sought because the ribonucleic acid (rna)-dependent deoxyribonucleic ac ... | 1974 | 15825395 |
| t-cell growth transformation by herpesvirus saimiri is independent of stat3 activation. | herpesvirus saimiri (saimirine herpesvirus 2) (hvs), a t-lymphotropic tumor virus, induces lymphoproliferative disease in several species of new world primates. in addition, strains of hvs subgroup c are able to transform t cells of old world primates, including humans, to permanently growing t-cell lines. in concert with the stp oncoprotein, the tyrosine kinase-interacting protein (tip) of hvs c488 is required for t-cell transformation in vitro and lymphoma induction in vivo. tip was previously ... | 2005 | 15827186 |
| comparison of susceptibility to sivmac239 infection between cd4(+) and cd4(+)8(+) t cells. | cd4-bearing t cells are the primary targets for human immunodeficiency virus type 1(hiv-1)/simian immunodeficiency virus (siv) infection. however, it is unclear whether the susceptibility of cd4-bearing t cells including cd4 single positive and cd4/8 double positive t cells to hiv/siv infection is the same or not. in this study, we compared the susceptibility to siv infection between cd4(+) and cd4(+)8(+) t cells, using herpesvirus saimiri (hvs)-transformed cd4(+) and cd4(+)8(+) t cells establis ... | 2005 | 15841338 |
| herpesvirus saimiri-based vector biodistribution using noninvasive optical imaging. | herpesvirus saimiri (hvs) is capable of infecting a range of human cell types with high efficiency and the viral genome persists as high copy number, circular, nonintegrated episomes which segregate to progeny upon cell division. this allows the hvs-based vector to stably transduce a dividing cell population and provide sustained transgene expression for an extended period of time both in vitro and in vivo. here we assess the dissemination of hvs-based vectors in vivo following intravenous and i ... | 2005 | 15889136 |
| small nuclear rnas encoded by herpesvirus saimiri upregulate the expression of genes linked to t cell activation in virally transformed t cells. | seven small nuclear rnas of the sm class are encoded by herpesvirus saimiri (hvs), a gamma herpesvirus that causes aggressive t cell leukemias and lymphomas in new world primates and efficiently transforms t cells in vitro. the herpesvirus saimiri u rnas (hsurs) are the most abundant viral transcripts in hvs-transformed, latently infected t cells but are not required for viral replication or transformation in vitro. we have compared marmoset t cells transformed with wild-type or a mutant hvs lac ... | 2005 | 15916956 |
| tyrosine phosphorylation of the tio oncoprotein is essential for transformation of primary human t cells. | human t cells are transformed to antigen-independent permanent growth in vitro upon infection with herpesvirus saimiri subgroup c strains. the viral oncoproteins required for this process, stpc and tip, could be replaced by tio, the oncoprotein of herpesvirus ateles. here we demonstrate that proliferation of lymphocytes transformed with tio-recombinant herpesvirus saimiri required the activity of src family kinases. src kinases had previously been identified as interaction partners of tio. this ... | 2005 | 16051843 |
| open reading frame 73 is required for herpesvirus saimiri a11-s4 episomal persistence. | herpesvirus saimiri (hvs) establishes a latent infection in which the viral genome persists as a non-integrated episome. analysis has shown that only open reading frames (orfs) 71-73 are transcribed in an in vitro model of hvs latency. orf73 also colocalizes with hvs genomic dna on host mitotic chromosomes and maintains the stability of hvs terminal-repeat-containing plasmids. however, it is not known whether orf73 is the only hvs-encoded protein required for episomal maintenance. in this study, ... | 2005 | 16186223 |
| the herpesvirus saimiri replication and transcription activator acts synergistically with ccaat enhancer binding protein alpha to activate the dna polymerase promoter. | the open reading frame (orf) 50 gene product, also known as the replication and transcription activator (rta), is an immediate-early gene which is well conserved among all gamma-2 herpesviruses and plays a pivotal role in regulating the latent-lytic switch. herpesvirus saimiri (hvs) orf 50a functions as a sequence-specific transactivator capable of activating delayed-early (de) gene expression via binding directly to an orf 50 response element (re) within the respective promoter. analysis of the ... | 2005 | 16227275 |
| herpesvirus saimiri immortalization of alpha beta and gamma delta human t-lineage cells derived from cd34+ intrathymic precursors in vitro. | herpesvirus saimiri (hvs), an agent that can infect many human cell types, has been shown to immortalize selectively tcr alpha beta + cd3+ t lymphocytes. human t cell precursors defined as cd34+cd3-cd4-cd8- were isolated from thymic samples and exposed to hvs in the presence of either il-2 or il-7. cultures lacking the virus were non-viable by day 15. test cultures, in contrast, showed a sustained proliferative activity lasting > 5 months, allowing the phenotypical and molecular analysis of the ... | 1996 | 8943575 |
| murine gammaherpesvirus 68 infection is associated with lymphoproliferative disease and lymphoma in balb beta2 microglobulin-deficient mice. | human gammaherpesvirus infections are associated with development of lymphoproliferative disease. understanding of the mechanisms of gammaherpesvirus lymphomagenesis during chronic infection in a natural host has been limited by the exquisite species specificity of human gammaherpesviruses and the expense of primates. murine gammaherpesvirus gammahv68 is genetically and biologically related to human gammaherpesviruses and herpesvirus saimiri and has been reported to be associated with lymphoprol ... | 2005 | 16282467 |
| specific sequence features, recognized by the smn complex, identify snrnas and determine their fate as snrnps. | the survival of motor neurons (smn) complex is essential for the biogenesis of spliceosomal small nuclear ribonucleoproteins (snrnps) as it binds to and delivers sm proteins for assembly of sm cores on the abundant small nuclear rnas (snrnas). using the conserved snrnas encoded by the lymphotropic herpesvirus saimiri (hvs), we determined the specific sequence and structural features of rnas for binding to the smn complex and for sm core assembly. we show that the minimal smn complex-binding doma ... | 2005 | 16314521 |
| association of herpesvirus saimiri tip with lipid raft is essential for downregulation of t-cell receptor and cd4 coreceptor. | lipid rafts are membrane microdomains that are proposed to function as platforms for both receptor signaling and trafficking. our previous studies have demonstrated that tip of herpesvirus saimiri (hvs), which is a t-lymphotropic tumor virus, is constitutively targeted to lipid rafts and interacts with cellular lck tyrosine kinase and p80 wd repeat-containing endosomal protein. through the interactions with lck and p80, hvs tip modulates diverse t-cell functions, which leads to the downregulatio ... | 2006 | 16352535 |
| herpesvirus saimiri-based gene delivery vectors. | herpesviruses possess a number of characteristics which make them promising gene delivery vectors. these include their capacity to package large amounts of heterologous dna and an ability to establish persistent, lifelong infections, where the viral genome remains as a circular non-integrated episome. herpesvirus saimiri (hvs) is the prototype gamma-2 herpesvirus and is currently being developed as a potential gene delivery vector. in addition to the above properties, hvs-based vectors have the ... | 2006 | 16475942 |
| regulation of intracellular signalling by the terminal membrane proteins of members of the gammaherpesvirinae. | the human gamma(1)-herpesvirus epstein-barr virus (ebv) and the gamma(2)-herpesviruses kaposi's sarcoma-associated herpesvirus (kshv), rhesus rhadinovirus (rrv), herpesvirus saimiri (hvs) and herpesvirus ateles (hva) all contain genes located adjacent to the terminal-repeat region of their genomes, encoding membrane proteins involved in signal transduction. designated 'terminal membrane proteins' (tmps) because of their localization in the viral genome, they interact with a variety of cellular s ... | 2006 | 16603506 |
| defective cd3zeta chain expression in herpesvirus saimiri (hvs)-derived t-cell lines in gastric adenocarcinoma. | low expression of the cd3zeta chain has been reported in patients with cancer and it has been suggested that tumor-derived factors are involved in its downregulation. the expression of cd3zeta chain was measured in t-cell lines from patients with gastric adenocarcinoma and healthy volunteers and grown in vitro for several months and, hence, in the absence of any tumor-derived factors. t-cell lines of mucosal origin were obtained by herpesvirus saimiri transformation from gastric cancer patients. ... | 2006 | 16616055 |
| platelets enhance cd4+ lymphocyte adhesion to extracellular matrix under flow conditions: role of platelet aggregation, integrins, and non-integrin receptors. | the purpose of this study was to examine the role of platelets in cd4+ t lymphocyte adhesion to subendothelial extracellular matrix (ecm). herpesvirus saimiri (hvs)-infected cd4+ t cells were incubated on ecm. an image analysis was used to evaluate t cell adhesion. under static condition, t cell activation with 4-alpha-phorbol 12-myristate 13-acetate (pma) resulted in a 2.6-fold increase in cell adhesion. however, adhesion was not affected by platelets. in contrast, under flow (200s(-1)), platel ... | 2006 | 16676073 |
| functional characterization of the complement control protein homolog of herpesvirus saimiri: arg-118 is critical for factor i cofactor activities. | herpesvirus saimiri (hvs) is a lymphotropic virus that causes t-cell lymphomas in new world primates. it encodes a structural homolog of complement control proteins named complement control protein homolog (ccph). previously, ccph has been shown to inhibit c3d deposition on target cells exposed to complement. here we have studied the mechanism by which it inactivates complement. we have expressed the soluble form of ccph in escherichia coli, purified to homogeneity and compared its activity to v ... | 2006 | 16760474 |
| h. saimiri tyrosine-kinase interacting protein inhibits tat function: a prototypic strategy for restricting hiv-1-induced cytopathic effects in immune cells. | herpesvirus saimiri (hvs)-transformed human t cells become permissive for x4 and r5 strains of human immunodeficiency virus type 1 (hiv-1), evidence that hvs-encoded proteins associated with t cell transformation enhance hiv-1 replication. analyzing the contribution of transformation-associated bicistronic hvs open reading frames (orf) to hiv-1 replication revealed expression of the second orf saimiri transformation-associated protein type c (stpc) conferred the permissive phenotype to t cells. ... | 2006 | 16780912 |
| stpc-based gene therapy targeting latent reservoirs of hiv-1. | the ability of hiv-1 to form latent reservoirs presents a major obstacle to eradication. one approach to elimination of the latent reservoir is induction therapy, whereby cells harboring latent virus are activated and therefore initiate virus replication. we have constructed a lentiviral vector encoding herpesvirus saimiri subgroup c saimiri transformation-associated protein (stpc), which has been shown to modulate hiv-1 replication, under the control of a cytomegalovirus promoter in order to de ... | 2006 | 16891001 |
| novel function of prothymosin alpha as a potent inhibitor of human immunodeficiency virus type 1 gene expression in primary macrophages. | cd8(+) t lymphocytes control human immunodeficiency virus type 1 (hiv-1) infection by a cytotoxic major histocompatibility complex-restricted pathway as well as by secretion of noncytotoxic soluble inhibitory factors. several components of cd8(+) cell supernatants have been identified that contribute to the latter activity. in this study we report that prothymosin alpha (protalpha), a protein found in the cell culture medium of the herpesvirus saimiri-transformed cd8(+) t-cell line, k#1 50k, has ... | 2006 | 16940531 |
| growth transformation of human t cells by herpesvirus saimiri requires multiple tip-lck interaction motifs. | lymphoma induction and t-cell transformation by herpesvirus saimiri strain c488 depends on two viral oncoproteins, stpc and tip. the major interaction partner of tip is the protein tyrosine kinase lck, a key regulator of t-cell activation. the lck binding domain (lbd) of tip comprises two interaction motifs, a proline-rich sh3 domain-binding sequence (sh3b) and a region with homology to the c terminus of src family kinase domains (cskh). in addition, biophysical binding analyses with purified lc ... | 2006 | 17005671 |
| nucleolar trafficking is essential for nuclear export of intronless herpesvirus mrna. | the nucleolus is the largest subnuclear structure and is plurifunctional in nature. here, we demonstrate that nucleolar localization of a key herpesvirus regulatory protein is essential for its role in virus mrna nuclear export. the herpesvirus saimiri orf57 protein is a nucleocytoplasmic shuttle protein that is conserved in all herpesviruses and orchestrates the nuclear export of viral intronless mrnas. we demonstrate that expression of the orf57 protein induces nucleolar redistribution of huma ... | 2006 | 17005724 |
| altered dynamics in lck sh3 upon binding to the lbd1 domain of herpesvirus saimiri tip. | the tip protein from herpesvirus saimiri interacts with the sh3 domain from the src-family kinase lck via a proline-containing sequence termed lbd1. src-family kinase sh3 domains related to lck have been shown to be dynamic in solution and partially unfold under physiological conditions. the rate of such partial unfolding is reduced by viral protein binding. to determine if the lck sh3 domain displayed similar behavior, the domain was investigated with hydrogen exchange and mass spectrometry. lc ... | 2006 | 17008721 |
| gene structure and expression of kaposi's sarcoma-associated herpesvirus orf56, orf57, orf58, and orf59. | though similar to those of herpesvirus saimiri and epstein-barr virus (ebv), the kaposi's sarcoma-associated herpesvirus (kshv) genome features more splice genes and encodes many genes with bicistronic or polycistronic transcripts. in the present study, the gene structure and expression of kshv orf56 (primase), orf57 (mta), orf58 (ebv bmrf2 homologue), and orf59 (dna polymerase processivity factor) were analyzed in butyrate-activated kshv(+) jsc-1 cells. orf56 was expressed at low abundance as a ... | 2006 | 17020939 |
| activation of non-canonical nf-kappab pathway mediated by stp-a11, an oncoprotein of herpesvirus saimiri. | although saimiri transforming protein (stp)-a11, an oncoprotein of herpesvirus saimiri, has been known to activate nf-kappab signaling pathway, the detailed mechanism has not been reported yet. we herein report that stp-a11 activates non-canonical nf-kappab pathway, resulting in p100 processing to p52. in addition, translocation of p52 protein (nf-kappab2) into the nucleus is observed by the expression of stp-a11. stp-a11-mediated processing of p100 to p52 protein requires proteosome-mediated pr ... | 2007 | 17028057 |
| herpesvirus saimiri (hvs)-transformed t-cell lines: a method to study mucosal t cells in inflammatory bowel disease. | | 2006 | 17060131 |
| cd4+ lymphocytes require platelets for adhesion to immobilized fibronectin in flow: role of beta(1) (cd29)-, beta(2) (cd18)-related integrins and non-integrin receptors. | the role of platelets in t-lymphocytes adhesion is not clear yet. herpesvirus saimiri (hvs)-infected cd4(+) t-lymphocytes were placed into polystyrene plates pre-coated with fibronectin. the adherent t-cells were enumerated by image analysis. under static condition, 38+/-10cells/mm(2) adhered and addition of gel-filtered platelets (gfp) and pma enhanced cell adhesion 4.3- and 4.1-fold. using pma plus gfp 11.9-fold enhancement in cell adhesion was achieved. in contrast, under flow (200s(-1)), nei ... | 2006 | 17087927 |
| the rta/orf50 transactivator proteins of the gamma-herpesviridae. | the replication and transcription activator protein, rta, is encoded by orf50 in kaposi's sarcoma-associated herpesvirus (kshv) and other known gammaherpesviruses including epstein-barr virus (ebv), rhesus rhadinovirus (rrv), herpesvirus saimiri (hvs), and murine herpesvirus 68 (mhv-68). each rta/orf50 homologue of each gammaherpesvirus plays a pivotal role in the initiation of viral lytic gene expression and lytic reactivation from latency. here we discuss the rta/orf50 of kshv in comparison to ... | 2007 | 17089794 |
| human herpesvirus 8-encoded proteins with potential roles in virus-associated neoplasia. | human herpesvirus 8 (hhv-8) is a gamma-2 herpesvirus, related genetically to simian herpesvirus saimiri (hvs), the prototype virus of this subgroup of the gammaherpesvirus subfamily. hhv-8 dna is present in all forms of kaposi's sarcoma (ks) and primary effusion lymphoma (pel), and in most forms of multicentric castleman's disease (mcd), especially in hiv infected individuals. of relevance to attempts to explain the molecular basis of hhv-8 associated neoplasia, are the unique genes specified by ... | 2007 | 17127298 |
| fcrgamma chain does not replace cd3zeta chain in cd3zeta-deficient t lymphocytes of patients with gastric adenocarcinoma. | defective cd3zeta chain expression has been reported in t lymphocytes of patients with inflammatory diseases, such as systemic lupus erythematosus or osteoarthritis, and with cancer. in lupus, the absent cd3zeta chain is replaced by the fcrgamma chain, rendering the t cells hyper responsive. however, there are no data on t lymphocytes from patients with cancer. in this study, the presence of the fcrgamma chain and its associated kinase, syk, was analysed in patients with gastric adenocarcinoma a ... | 2007 | 17134755 |
| familial nk cell deficiency associated with impaired il-2- and il-15-dependent survival of lymphocytes. | we previously reported the clinical phenotype of two siblings with a novel inherited developmental and immunodeficiency syndrome consisting of severe intrauterine growth retardation and the impaired development of specific lymphoid lineages, including transient cd8 alphabeta t lymphopenia and a persistent lack of blood nk cells. we describe here the elucidation of a plausible underlying pathogenic mechanism, with a cellular phenotype of impaired survival of both fresh and herpesvirus saimiri-tra ... | 2006 | 17142786 |
| histone modification pattern of the t-cellular herpesvirus saimiri genome in latency. | herpesvirus saimiri (hvs) subgroup c strains are able to growth transform human t lymphocytes in vitro. the stably persisting and nonintegrating hvs episome represents an optimal prerequisite for the investigation of the epigenetic state of latent herpesvirus genomes in vitro. quantitative chromatin immunoprecipitation experiments using seven different histone acetylation- or methylation-specific antibodies revealed repressive marks at four lytic gene promoters and a variable pattern at the weak ... | 2007 | 17151105 |
| herpesvirus saimiri stp-a oncoprotein utilizes src family protein tyrosine kinase and tumor necrosis factor receptor-associated factors to elicit cellular signal transduction. | the saimiri transforming protein oncogene, called stp-a, of herpesvirus saimiri (hvs) subgroup a is not required for viral replication but is required for lymphoid cell immortalization in culture and lymphoma induction in primates. here we report that stp-a interacts with cellular tumor necrosis factor receptor-associated factors (traf2 and traf6) and src family protein tyrosine kinases (sf-ptks) in a genetically and functionally separable manner and that each interaction constitutively elicits ... | 2007 | 17182673 |
| generation of cd4+ and cd8+ t-cell clones from pbls of hiv-1 infected subjects using herpesvirus saimiri. | | 1996 | 8898759 |
| herpesvirus saimiri terminal membrane proteins modulate hiv-1 replication by altering nef and tat functions. | herpesvirus saimiri (hvs)-transformed human t cells expressing terminal membrane proteins (tmps) tyrosine kinase interacting protein (tip) and saimiri transformation associated protein strain c (stpc) are highly permissive for r5 and x4 strains of hiv-1. stpc expression enhances replication of r5 and x4 strains of hiv-1 and induces latent reservoirs of replication competent hiv-1 in cell lines derived from t cells or monocytes. paradoxically tip expression restricts replication and cytopathic ef ... | 2007 | 17266559 |
| herpesvirus saimiri episomal persistence is maintained via interaction between open reading frame 73 and the cellular chromosome-associated protein mecp2. | herpesvirus saimiri (hvs) is the prototype gamma-2 herpesvirus, which naturally infects the squirrel monkey saimiri sciureus, causing an asymptomatic but persistent infection. the latent phase of gamma-2 herpesviruses is characterized by their ability to persist in a dividing cell population while expressing a limited subset of latency-associated genes. in hvs only three genes, open reading frame 71 (orf71), orf72, and orf73, are expressed from a polycistronic mrna. orf73 has been shown to be th ... | 2007 | 17267510 |
| stp-a11, an oncoprotein of herpesvirus saimiri augments both nf-kappab and ap-1 transcription activity through traf6. | herpesvirus saimiri (hvs), a member of the gamma-herpesvirus family, encodes an oncoprotein called saimiri transforming protein (stp) which is required for lymphoma induction in non-human primates. however, a detailed mechanism of stp-a11-induced oncogenesis has not been revealed yet. we first report that stp-a11 oncoprotein interacts with tnf-alpha receptor-associated factor (traf) 6 in vivo and in vitro. mutagenesis analysis of the traf6-binding motif (10)pqende(15) in stp-a11 reveals that glu ... | 2007 | 17334229 |
| the challenge of viral snrnps. | some gammaherpesviruses encode nuclear noncoding rnas (ncrnas) that assemble with host proteins. their conservation and abundance implies that they serve important functions for the virus. this paper focuses on our studies of three classes of nuclear noncoding herpesvirus rnas. (1) ebers 1 and 2 are expressed by epstein-barr virus in latent infection of human b lymphocytes. recent studies revealed three sites on eber1 that associate with ribosomal protein l22. in addition, heterokaryon assays ha ... | 2006 | 17381320 |
| mutagenesis of the herpesvirus saimiri terminal repeat region reveals important elements for virus production. | deletion of the terminal repeats (tr) from herpesvirus saimiri (hvs) renders it unable to produce infectious virus or generate plaques. however, a tr-deleted hvs bacterial artificial chromosome can form replication compartments. complementation of this mutant shows that one copy of the tr, plus the right junction of the genome with the tr, is sufficient for efficient plaque formation and generation of infectious virus. within the tr unit, the region around the cleavage site of the genome appears ... | 2007 | 17428860 |
| stp-c, an oncoprotein of herpesvirus saimiri augments the activation of nf-kappab through ubiquitination of traf6. | herpesvirus saimiri (hvs), a member of the gamma-herpesvirus family, encodes an oncoprotein called saimiri transforming protein (stp) which is required for lymphoma induction in non-human primates. previous study has shown that stp-c, an oncoprotein of hvs, activates nf-kappab signaling pathway. however, the detailed mechanism of stp-c-mediated nf-kappab activation has not been reported yet. we first report that stp-c interacts with traf6 protein in vivo and in vitro and further investigation sh ... | 2007 | 17562285 |
| kaposi's sarcoma-associated herpesvirus orf57 protein enhances mrna accumulation independently of effects on nuclear rna export. | the orf57 protein expressed by kaposi's sarcoma-associated herpesvirus (kshv) during lytic replication is essential for kshv virion production. orf57 enhances gene expression by increasing accumulation of target gene mrnas. orf57 interacts with the cellular export factor ref and with rna, suggesting that it may provide target mrnas with access to ref, which mediates nuclear rna export by binding to tap/nxf1. a mutational analysis of orf57 was performed to study the role of ref binding, rna inter ... | 2007 | 17609285 |
| herpesvirus saimiri orf57: a post-transcriptional regulatory protein. | herpesvirus saimiri (hvs) is the prototype gamma-2 herpesvirus and is a useful model to study the basic mechanisms of lytic replication in this herpesvirus subfamily. this review focuses upon the role of an essential lytic protein, orf57, which is functionally conserved in all classes of herpesviruses. orf57 is a multidomain, multifunctional protein responsible for both activation and repression of viral gene expression at a post-transcriptional level. orf57-mediated repression of gene expressio ... | 2008 | 17981766 |
| herpesvirus saimiri-transformed human cd4+ t cells can provide polyclonal b cell help via the cd40 ligand as well as the tnf-alpha pathway and through release of lymphokines. | we have developed human cd4+ t cell lines from the pbl of normal donors by infection with herpesvirus saimiri (hvs), to evaluate functional properties of these immortalized lymphocytes. in this report, we characterize two such cd4+ t cell lines, chcd4 and mhcd4, which were derived from two different donors. these cells grew independent of exogenous il-2 stimulation for over 1 yr, and expressed surface markers (cd25+, cd69+, hla-dr+, and b7+) associated with an activated t cell phenotype. both li ... | 1996 | 8892618 |
| herpesvirus saimiri transformation may help disclose inherent functional defects of mucosal t lymphocytes in patients with gastric adenocarcinoma. | to dissect the phenotypic and functional features of mucosal t lymphocytes in patients with gastric adenocarcinoma, we have used the herpesvirus saimiri transformation procedure to achieve t-cell lines from gastric origin. once achieved, cell function was assessed by in vitro stimulation with mitogens. cd2-specific monoclonal antibodies (alpha-cd2), alone or in combination with interleukin (il)-2, rendered fewer counts in patients (34 408+/-3965 and 52 157+/-6473 c.p.m., respectively) than in co ... | 2008 | 18283295 |
| production of an infectious herpesvirus saimiri-based episomally maintained amplicon system. | viral vectors have a number of obstacles to overcome for effective gene therapy, including immune stimulation, packaging potential and cell tropism. herpesvirus saimiri (hvs) has many favourable traits including, a large packaging capability, wide cell tropism, and the ability to episomally persist as an artificial chromosome. to further develop hvs as a gene therapy vector we aim to produce a safe disabled hvs-based recombinant viral system for gene therapy applications. an hvs recombinant vira ... | 2008 | 18328588 |
| herpesvirus saimiri transformation of human t lymphocytes. | viral transformation of t cells is an effective method for obtaining large numbers of t cells that are easily maintained in the laboratory. this unit describes a method for generating antigen-independent, virally-transformed t cells using a t-lymphotropic primate gamma-2 herpesvirus, herpesvirus saimiri (hvs; strain c488). support protocols for preparing and titrating hsv c488 stocks and testing the functional status of transformed t cells are also included. | 2004 | 18432932 |
| nf-kappab activation by the viral oncoprotein stpc enhances ifn-gamma production in t cells. | interferon-gamma (ifn-gamma) is an essential regulator of innate and adaptive immune responses and a hallmark of the th1 t-cell subset. it is produced at high levels by human t lymphocytes upon transformation with herpesvirus saimiri, which depends on the expression of the viral oncoproteins saimiri transformation-associated protein of subgroup c (stpc) and tyrosine kinase-interacting protein (tip). here, we show that ifn-gamma production was induced by tip in jurkat t cells. stpc by itself did ... | 2008 | 18560378 |
| human herpesvirus 8 infections in patients with immunodeficiencies. | in 1994, chang et al described a novel herpesvirus in tissues from patients with kaposi sarcoma, referred to as kaposi sarcoma herpesvirus or human herpesvirus 8. they used a very sophisticated technique of molecular biology to isolate unknown dna sequences from kaposi sarcoma lesions, which were not present in normal tissues. it turned out that these sequences corresponded to a previously unrecognized gamma herpesvirus highly homologous to human herpesvirus 4 (epstein-barr virus) and to herpesv ... | 2008 | 18570975 |
| viral nucleolar localisation signals determine dynamic trafficking within the nucleolus. | localisation of both viral and cellular proteins to the nucleolus is determined by a variety of factors including nucleolar localisation signals (nolss), but how these signals operate is not clearly understood. the nucleolar trafficking of wild type viral proteins and chimeric proteins, which contain altered nolss, were compared to investigate the role of nolss in dynamic nucleolar trafficking. three viral proteins from diverse viruses were selected which localised to the nucleolus; the coronavi ... | 2008 | 18775548 |
| mapping the minimal regions within the orf73 protein required for herpesvirus saimiri episomal persistence. | herpesvirus saimiri (hvs) establishes a persistent infection in which the viral genome persists as a circular non-integrated episome. orf73 tethers hvs episomes to host mitotic chromosomes, allowing episomal persistence via an interaction with the chromosome-associated protein, mecp2. here we demonstrate that orf73 also interacts with the linker histone h1 via its c terminus, suggesting it associates with multiple chromosome-associated proteins. in addition, we show that the c terminus is also r ... | 2008 | 18931082 |
| reduction in rna levels rather than retardation of translation is responsible for the inhibition of major histocompatibility complex class i antigen presentation by the glutamic acid-rich repeat of herpesvirus saimiri open reading frame 73. | herpesvirus saimiri (hvs) establishes a persistent infection in squirrel monkeys by maintaining its episome within t lymphocytes. the product of open reading frame 73 (orf73) plays a key role in episomal maintenance and is the functional homologue of epstein-barr virus ebna1 and kaposi's sarcoma-associated herpesvirus lana1 proteins. there is little sequence homology among these proteins, although all contain a central domain of repeating amino acids. the repeat domains of ebna1 and lana1 enhanc ... | 2009 | 18945762 |
| multi-transmembrane protein k15 of kaposi's sarcoma-associated herpesvirus targets lyn kinase in the membrane raft and induces nfat/ap1 activities. | viral proteins of gamma-2 herpesviruses, such as lmp2a of epstein barr virus (ebv) and tip of herpesvirus saimiri (hvs) dysregulate lymphocyte signaling by interacting with src family kinases. k15 open reading frame of kaposi's sarcoma associated herpesvirus (kshv), located at the right end of the viral genome, encodes several splicing variants differing in numbers of transmembrane domains. previously, we demonstrated that the cytoplasmic tail of the k15 protein interfered with b cell receptor s ... | 2008 | 18985015 |
| role of amphipathic helix of a herpesviral protein in membrane deformation and t cell receptor downregulation. | lipid rafts are membrane microdomains that function as platforms for signal transduction and membrane trafficking. tyrosine kinase interacting protein (tip) of t lymphotropic herpesvirus saimiri (hvs) is targeted to lipid rafts in t cells and downregulates tcr and cd4 surface expression. here, we report that the membrane-proximal amphipathic helix preceding tip's transmembrane (tm) domain mediates lipid raft localization and membrane deformation. in turn, this motif directs tip's lysosomal traff ... | 2008 | 19023411 |
| the alcelaphine herpesvirus-1 orf 57 encodes a nuclear shuttling protein. | alcelaphine herpesvirus-1 (alhv-1) is a gamma(2) rhadinovirus associated with malignant catarrhal fever (mcf) in cattle. orf 57 is well conserved among gammaherpesviruses and it has been shown that the orf 57 gene products of herpesvirus saimiri (hvs), kaposi's sarcoma-associated herpesvirus (kshv) and epstein-barr virus (ebv) play an important role in regulating viral gene expression. the alhv-1 orf 57 gene product has not been characterized. in the accompanying paper we have demonstrated that ... | 2009 | 19031003 |
| selective uptake of small rna molecules in the virion of murine gammaherpesvirus 68. | noncoding rnas are a feature of many herpesvirus genomes. they include micrornas, whose function is the subject of intense investigation, in addition to longer rna molecules such as the epstein-barr virus-encoded rnas and herpesvirus saimiri u rnas, which have been known for some time but whose function is still not well defined. murine gammaherpesvirus 68 (mhv-68) encodes eight viral trna-like molecules (vtrnas) of unknown function. investigating the kinetics of expression of the vtrnas, we obs ... | 2009 | 19109392 |