Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
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| disruption of the gene encoding the gammahv68 v-gpcr leads to decreased efficiency of reactivation from latency. | murine gammaherpesvirus 68 (gammahv68; mhv68) infection of mice has been a useful model for characterizing the role of conserved herpesvirus genes in pathogenesis. one of the well conserved genes among gamma2-herpesvirus, gene 74, encodes a viral g-protein coupled receptor (v-gpcr). to examine the role of the gammahv68 v-gpcr in pathogenesis we have generated a mutant virus in which 440 base pairs of the gene 74 open reading frame have been deleted (gammahv68v-gpcrdelta440). this deletion did no ... | 2003 | 12667789 |
| disruption of gammaherpesvirus 68 gene 50 demonstrates that rta is essential for virus replication. | gammaherpesvirus pathogenesis is dependent on the ability of these viruses to establish a lifelong latent infection and the ability to reactivate from latency. immediate-early genes of theses viruses are thought to be critical regulators of lytic replication and reactivation from latency. the gene 50-encoded rta is the only immediate-early gene product that appears to be conserved among all characterized gammaherpesviruses. previous studies have demonstrated that, in epstein-barr virus (ebv), ka ... | 2003 | 12719566 |
| selective gene expression of latent murine gammaherpesvirus 68 in b lymphocytes. | intranasal infection of mice with murine gammaherpesvirus 68 (mhv-68), a virus genetically related to the human pathogen kaposi's sarcoma-associated herpesvirus, results in a persistent, latent infection in the spleen and other lymphoid organs. here, we have determined the frequency of virus infection in splenic dendritic cells, macrophages, and several b-cell subpopulations, and we quantified cell type-dependent virus transcription patterns. the frequencies of virus genome positive cells were m ... | 2003 | 12805429 |
| establishment and maintenance of gammaherpesvirus latency are independent of infective dose and route of infection. | gammaherpesviruses such as epstein-barr virus and kaposi's sarcoma-associated herpesvirus are important human pathogens that establish long-term latent infections. understanding of the initiation and maintenance of latent infections has important implications for the prevention and treatment of gammaherpesvirus-related diseases. although much is known about gammaherpesvirus pathogenesis, it is unclear how the infectious dose of a virus influences its ability to establish latent infection. to exa ... | 2003 | 12805472 |
| exacerbation of experimental autoimmune encephalomyelitis in rodents infected with murine gammaherpesvirus-68. | viral infections have long been suspected to play a role in the pathogenesis of multiple sclerosis. in the present study, two different rodent models of experimental autoimmune encephalomyelitis (eae) were used to demonstrate the ability of murine gammaherpesvirus-68 (gammahv-68) to exacerbate development of neurological symptoms. sjl mice received uv-inactivated gammahv-68 or intranasalgammahv-68, followed by immunization against proteolipid-protein peptide 139-151. infected mice became moribun ... | 2003 | 12811845 |
| long-term latent murine gammaherpesvirus 68 infection is preferentially found within the surface immunoglobulin d-negative subset of splenic b cells in vivo. | murine gammaherpesvirus 68 (gammahv68; also known as mhv-68) can establish a latent infection in both inbred and outbred strains of mice and, as such, provides a tractable small-animal model to address mechanisms and cell types involved in the establishment and maintenance of chronic gammaherpesvirus infection. latency can be established at multiple anatomic sites, including the spleen and peritoneum; however, the contribution of distinct cell types to the maintenance of latency within these res ... | 2003 | 12857900 |
| nf-kappab inhibits gammaherpesvirus lytic replication. | nasopharyngeal carcinoma, kaposi's sarcoma, and b-cell lymphomas are human malignancies associated with gammaherpesvirus infections. members of this virus family are characterized by their ability to establish latent infections in lymphocytes. the latent viral genome expresses very few gene products. the infected cells are therefore poorly recognized by the host immune system, allowing the virus to persist for long periods of time. we sought to identify the cell-specific factors that allow these ... | 2003 | 12857922 |
| the gammaherpesvirus chemokine binding protein binds to the n terminus of cxcl8. | viruses encode proteins that disrupt chemokine responses. the murine gammaherpesvirus 68 gene m3 encodes a chemokine binding protein (vckbp-3) which has no sequence similarity to chemokine receptors but inhibits chemokine receptor binding and activity. we have used a panel of cxcl8 analogs to identify the structural requirements for cxcl8 to bind to vckbp-3 in a scintillation proximity assay. our data suggest that vckbp-3 acts by mimicking the binding of chemokine receptors to cxcl8. | 2003 | 12857930 |
| murid herpesvirus 4 strain 68 m2 protein is a b-cell-associated antigen important for latency but not lymphocytosis. | this work describes analyses of the function of the murid herpesvirus 4 strain 68 (mhv-68) m2 gene. a frameshift mutation was made in the m2 open reading frame that caused premature termination of translation of m2 after amino acid residue 90. the m2 mutant showed no defect in productive replication in vitro or in lungs after infection of mice. likewise, the characteristic transient increase in spleen cell number, vbeta4 t-cell-receptor-positive cd8(+) t-cell mononucleosis, and establishment of ... | 2003 | 12915582 |
| mice deficient in the x-linked lymphoproliferative disease gene sap exhibit increased susceptibility to murine gammaherpesvirus-68 and hypo-gammaglobulinemia. | x-linked lymphoproliferative disease is characterized by immune dysregulation and uncontrolled lymphoproliferation on exposure to epstein-barr virus (ebv). this disease has been attributed to mutations in the sap gene (also denominated as sh2d1a or dshp). to delineate the role of sap in the pathophysiology of x-linked lymphoproliferative disease, a strain of sap-deficient mice has been generated by deleting exon 2 of the gene. after infection with murine gammaherpesvirus-68, which is homologous ... | 2003 | 12966553 |
| transcription program of murine gammaherpesvirus 68. | murine gammaherpesvirus 68 (mhv-68 [also referred to as gammahv68]) is phylogenetically related to kaposi's sarcoma-associated herpesvirus (kshv [also referred to as hhv-8]) and epstein-barr virus (ebv). however, unlike kshv or ebv, mhv-68 readily infects fibroblast and epithelial cell lines derived from several mammalian species, providing a system to study productive and latent infections as well as reactivation of gammaherpesviruses in vivo and in vitro. to carry out rapid genome-wide analysi ... | 2003 | 12970434 |
| cox-2 induction during murine gammaherpesvirus 68 infection leads to enhancement of viral gene expression. | the murine gammaherpesvirus 68 (mhv-68 or gammahv-68) model provides many advantages for studying virus-host interactions involved in gammaherpesvirus replication, including the role of cellular responses to infection. we examined the effects of cellular cyclooxygenase-2 (cox-2) and its by-product prostaglandin e(2) (pge(2)) on mhv-68 gene expression and protein production following de novo infection of cultured cells. western blot analyses revealed an induction of cox-2 protein in mhv-68-infect ... | 2003 | 14610197 |
| an internal ribosome entry site directs translation of the murine gammaherpesvirus 68 mk3 open reading frame. | the gammaherpesviruses characteristically drive the proliferation of latently infected lymphocytes. the murine gammaherpesvirus 68 (mhv-68) mk3 protein contributes to this process in vivo by evading cd8(+)-t-cell recognition during latency, as well as during lytic infection. we analyzed some of the molecular mechanisms that control mk3 expression. no dedicated mk3 mrna was detected. instead, the mk3 open reading frame (orf) was transcribed as part of a bicistronic mrna, downstream of a previousl ... | 2003 | 14645566 |
| identification of proteins associated with murine gammaherpesvirus 68 virions. | murine gammaherpesvirus 68 (mhv68 [also known as gammahv-68]) is distinguished by its ability to replicate to high titers in cultured cells, making it an excellent candidate for studying gammaherpesvirus virion composition. extracellular mhv68 virions were isolated, and abundant virion-associated proteins were identified by mass spectrometry. five nucleocapsid protein homologues, the tegument protein homologue encoded by open reading frame (orf) 75c, and envelope glycoproteins b and h were detec ... | 2003 | 14645600 |
| 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 |
| disruption of ccl21-induced chemotaxis in vitro and in vivo by m3, a chemokine-binding protein encoded by murine gammaherpesvirus 68. | chemokine-binding proteins represent a novel class of antichemokine agents encoded by poxviruses and herpesviruses. one such protein is encoded by the m3 gene present in the murine gammaherpesvirus 68 (mhv-68) genome. the m3 gene encodes a secreted 44-kda protein that binds with high affinity to certain murine and human chemokines and has been shown to block chemokine signaling in vitro. however, there has been no direct evidence that m3 blocks chemokine activity in vivo, nor has the nature of m ... | 2003 | 12477865 |
| the phd/lap-domain protein m153r of myxomavirus is a ubiquitin ligase that induces the rapid internalization and lysosomal destruction of cd4. | the genomes of several poxviruses contain open reading frames with homology to the k3 and k5 genes of kaposi's sarcoma-associated herpesvirus (kshv) and the k3 gene of murine gammaherpesvirus 68, which target major histocompatibility complex class i (mhc-i) as well as costimulatory molecules for proteasomal or lysosomal degradation. the homologous gene product of myxomavirus (mv), m153r, was recently shown to reduce the cell surface expression of mhc-i. in addition, normal mhc-i surface expressi ... | 2003 | 12502858 |
| the m4 gene of murine gammaherpesvirus modulates productive and latent infection in vivo. | murine gammaherpesvirus 68 (mhv-68) infection of mice represents a viable small-animal model for the study of gammaherpesvirus pathogenesis. mhv-76 is a deletion mutant of mhv-68, which lacks four mhv-68-specific genes (m1 to m4) and eight viral trna-like sequences at the 5' end of the genome. these genes are implicated in latency and/or immune evasion. consequently, mhv-76 is attenuated in the acute phase of in vivo infection with respect to mhv-68. little is known about the role of m4 in viral ... | 2004 | 14694108 |
| different functional capacities of latent and lytic antigen-specific cd8 t cells in murine gammaherpesvirus infection. | gammaherpesviruses can persist in the host in the face of an aggressive immune response. t cells recognize ags expressed in both the productive and latent phases of the virus life cycle, however little is known about their relative roles in the long-term control of the infection. in this study we used the murine gammaherpesvirus 68 model system to investigate the relative properties of cd8 t cells recognizing lytic and latent viral ags. we report that the cd8 t cell response to lytic phase epito ... | 2004 | 14707099 |
| protection against wild-type murine gammaherpesvirus-68 latency by a latency-deficient mutant. | a murine gammaherpesvirus-68 (mhv-68) mutant with deregulated transcription of its orf50 transactivator was severely impaired in latency establishment. the deregulated virus showed reduced immunogenicity, probably reflecting a lower antigen load. however, it still elicited effective immunity to a subsequent wild-type (wt) virus challenge. infection was not completely prevented, but was very substantially reduced in extent and the long-term level of wt viral dna in lungs and spleens remained low. ... | 2004 | 14718627 |
| forced lytic replication impairs host colonization by a latency-deficient mutant of murine gammaherpesvirus-68. | a regulated switch between latent and lytic gene expression is common to all known herpesviruses. however, the effects on host colonization of altering this switch are largely unknown. we deregulated the transcription of the gene encoding the major lytic transactivator of murine gammaherpesvirus-68, orf50, by inserting a new and powerful promoter element in its 5' untranslated region. in vitro, the mutant virus (m50) transcribed orf50 at a high level and showed more rapid lytic spread in permiss ... | 2004 | 14718628 |
| the gammaherpesvirus chemokine binding protein can inhibit the interaction of chemokines with glycosaminoglycans. | chemokines are small glycosaminoglycan (gag) binding proteins that direct the migration of leukocytes by signaling through g protein coupled receptors (gpcr). many viruses encode proteins that disrupt chemokine responses. the murine gammaherpesvirus-68 gene m3 encodes a chemokine binding protein (vckbp-3), which has no sequence similarity to chemokine receptors. initial characterization of vckbp-3 showed that it inhibits receptor binding and chemokine-induced calcium influx. the structural requi ... | 2004 | 14734646 |
| 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 |
| t cell reactivity during infectious mononucleosis and persistent gammaherpesvirus infection in mice. | intranasal infection of mice with murine gammaherpesvirus 68 causes a dramatic increase in numbers of activated cd8(+) t cells in the blood, analogous in many respects to ebv-induced infectious mononucleosis in humans. in the mouse model, this lymphocytosis has two distinct components: an early, conventional virus-specific cd8(+) t cell response, and a later response characterized by a dramatic increase among cd8(+) t cells that bear vbeta4(+) tcrs. we previously demonstrated that vbeta4(+)cd8(+ ... | 2004 | 14978113 |
| vaccine potential of a murine gammaherpesvirus-68 mutant deficient for orf73. | a murine gammaherpesvirus (mhv-68) containing a deletion of the putative plasmid maintenance protein orf73 exhibits a severe latency deficit. in this study the ability of an orf73 deletion mutant (delta73) to confer in vivo protection against subsequent challenge with wild-type virus has been examined. vaccination studies have shown that delta73 vaccination reduced latent infection of wild-type challenge virus to a level below the limit of detection. these results indicate that a live-attenuated ... | 2004 | 14993644 |
| differential activation of murine herpesvirus 68- and kaposi's sarcoma-associated herpesvirus-encoded orf74 g protein-coupled receptors by human and murine chemokines. | infection of mice with murine gammaherpesvirus 68 (mhv-68) is a well-characterized small animal model for the study of gammaherpesvirus infection. mhv-68 belongs to the same herpesvirus family as herpesvirus saimiri (hvs) of new world squirrel monkeys and human herpesvirus 8 (hhv-8) (also referred to as kaposi's sarcoma-associated herpesvirus [kshv]). the open reading frame orf74 of hvs, kshv, and mhv-68 encodes a protein with homology to g protein-coupled receptors and chemokine receptors in pa ... | 2004 | 15016856 |
| cytokines and costimulatory molecules in the immune response to murine gammaherpesvirus-68. | murine gammaherpesvirus 68 (mhv-68) infection of mice provides a useful small animal model for studying gammaherpesvirus pathogenesis and immunity. recent work has elucidated the cytokine and chemokine profiles during mhv-68 infection and has identified some of the costimulatory interactions that are important for an effective immune response to this virus. several themes emerge from this work. there is a differential requirement for certain cytokines and costimulatory molecules in the acute and ... | 2004 | 15018658 |
| mouse strain differences in the chemokine response to acute lung infection with a murine gammaherpesvirus. | numerous mouse strain-based differences in the immune response and in susceptibility to numerous pathogens have been described, but it is not known if these differences extend to chemokine responses to viral infection of the lungs. to define mouse strain-based differences in the host chemokine response and susceptibility to infection with murine gammaherpesvirus-68 (mhv-68), we compared the induced chemokine response to mhv-68 infection in the lungs of balb/c and c57bl/6 mice at 1-15 days post-i ... | 2004 | 15018663 |
| vaccination with inactivated murine gammaherpesvirus 68 strongly limits viral replication and latency and protects type i ifn receptor knockout mice from a lethal infection. | human gammaherpesviruses such as epstein-barr virus (ebv) cause lifelong infections and associated diseases, including malignancies, and the development of an effective vaccine against this class of viral infections is of considerable interest. the murine herpesvirus 68 (mhv-68) model provides a useful experimental setting to investigate the immune response to gammaherpesvirus infections and to evaluate the efficacy of vaccination strategies. in this study, we tested a heat-inactivated mhv-68 va ... | 2004 | 15063566 |
| murine gammaherpesvirus 68 lacking gp150 shows defective virion release but establishes normal latency in vivo. | all gammaherpesviruses encode a virion glycoprotein positionally homologous to epstein-barr virus gp350. these glycoproteins are thought to be involved in cell binding, but little is known of the roles they might play in the whole viral replication cycle. we have analyzed the contribution of murine gammaherpesvirus 68 (mhv-68) gp150 to viral propagation in vitro and host colonization in vivo. mhv-68 lacking gp150 was viable and showed normal binding to fibroblasts and normal single-cycle lytic r ... | 2004 | 15113892 |
| murine gammaherpesvirus 68 open reading frame 31 is required for viral replication. | murine gammaherpesvirus 68 (mhv-68) is genetically related to the human gammaherpesviruses, kaposi's sarcoma-associated herpesvirus (kshv/hhv-8) and epstein-barr virus (ebv). it has been proposed as a model for gammaherpesvirus infection and pathogenesis. open reading frame 31 (orf31) is conserved among the beta- and gammaherpesvirinae subfamily, and there is no known mammalian homologue of this protein. the function of mhv-68 orf31 and its viral homologues has not yet been determined. we descri ... | 2004 | 15163752 |
| identification of a region of the virus genome involved in murine gammaherpesvirus 68-induced splenic pathology. | infection with the murine gammaherpesvirus mhv-68 has profound effects on splenic and mediastinal lymph node pathology in mice which lack the interferon-gamma receptor (ifn-gamma r(-/-)). in these mice mhv-68 infection causes fibrosis and loss of lymphocytes in the spleen and the mediastinal lymph node as well as interstitial pulmonary fibrosis and fibrotic changes in the liver. the changes are associated with transient elevated latent virus loads in the spleen. four independent virus mutants wi ... | 2004 | 15166421 |
| an optimized cd4 t-cell response can control productive and latent gammaherpesvirus infection. | cd4 t cells are important for control of infection with murine gammaherpesvirus 68 (gamma hv68), but it is not known whether cd4 t cells function via provision of help to other lymphocyte subsets, such as b cells and cd8 t cells, or have an independent antiviral function. moreover, under conditions of natural infection, the cd4 t-cell response is not sufficient to eliminate infection. to determine the functional capacities of cd4 t cells under optimal or near-optimal conditions and to determine ... | 2004 | 15194758 |
| critical role of cd4 t cells in an antibody-independent mechanism of vaccination against gammaherpesvirus latency. | we have previously demonstrated that it is possible to effectively vaccinate against long-term murine gammaherpesvirus 68 (gamma hv68) latency by using a reactivation-deficient virus as a vaccine (s. a. tibbetts, j. s. mcclellan, s. gangappa, s. h. speck, and h. w. virgin iv, j. virol. 77:2522-2529, 2003). immune antibody was capable of recapitulating aspects of this vaccination. this led us to determine whether antibody is required for vaccination against latency. using mice lacking antigen-spe ... | 2004 | 15194759 |
| murine gammaherpesvirus-68 elicits robust levels of interleukin-12 p40, but not interleukin-12 p70 production, by murine microglia and astrocytes. | murine gammaherpesvirus-68 (gamma hv-68) is a tractable model to investigate the pathophysiology of human gammaherpesvirus infections, including epstein-barr virus (ebv). herpesvirus infections are thought to play a role in the pathology of damaging, inflammatory diseases states of the central nervous system (cns), such as multiple sclerosis. the ability of the host to mount a strong cell-mediated immune response is critical in determining the outcome of viral infections. interleukin (il)-12 is ... | 2004 | 15204922 |
| expression in a recombinant murid herpesvirus 4 reveals the in vivo transforming potential of the k1 open reading frame of kaposi's sarcoma-associated herpesvirus. | murid herpesvirus 4 (commonly called mhv-68) is closely related to kaposi's sarcoma-associated herpesvirus (kshv) and provides an excellent model system for investigating gammaherpesvirus-associated pathogenesis. mhv-76 is a naturally occurring deletion mutant of mhv-68 that lacks 9,538 bp of the left end of the unique portion of the genome encoding nonessential pathogenesis-related genes. the kshv k1 protein has been shown to transform rodent fibroblasts in vitro and common marmoset t lymphocyt ... | 2004 | 15280496 |
| il-15-independent proliferative renewal of memory cd8+ t cells in latent gammaherpesvirus infection. | il-15 is known to be critical in the homeostasis of ag-specific memory cd8(+) t cells following acute viral infection. however, little is known about the homeostatic requirements of memory cd8(+) t cells during a latent viral infection. we have used the murine gammaherpesvirus-68 (mhv-68) model system to investigate whether il-15 is necessary for the maintenance of memory cd8(+) t cells during a latent viral infection. il-15 is not essential either for the initial control of mhv-68 infection or ... | 2004 | 15294989 |
| identification of cis sequences required for lytic dna replication and packaging of murine gammaherpesvirus 68. | human gammaherpesviruses are associated with lymphomas and other malignancies. murine gammaherpesvirus 68 (mhv-68) infection of mice has emerged as a model for understanding gammaherpesvirus pathogenesis in vivo. in contrast to human gammaherpesviruses, mhv-68 replicates in permissive cell lines in a robust manner, presenting an efficient model to study the basic mechanisms for dna replication and recombination processes. in addition, mhv-68 also infects a broad range of cells of different tissu ... | 2004 | 15308708 |
| generation of a latency-deficient gammaherpesvirus that is protective against secondary infection. | kaposi's sarcoma-associated herpesvirus and murine gammaherpesvirus-68 (mhv-68) establish latent infections and are associated with various types of malignancies. they are members of the gamma-2 herpesvirus subfamily and encode a replication and transcriptional activator, rta, which is necessary and sufficient to disrupt latency and initiate the viral lytic cycle in vitro. we have constructed a recombinant mhv-68 virus that overexpresses rta. this virus has faster replication kinetics in vitro a ... | 2004 | 15308716 |
| in vivo function of a gammaherpesvirus virion glycoprotein: influence on b-cell infection and mononucleosis. | the human gammaherpesviruses epstein-barr virus and kaposi sarcoma-associated herpesvirus both contain a glycoprotein (gp350/220 and k8.1, respectively) that mediates binding to target cells and has been studied in great detail in vitro. however, there is no direct information on the role that these glycoproteins play in pathogenesis in vivo. infection of mice by murid herpesvirus 4 strain 68 (mhv-68) is an established animal model for gammaherpesvirus pathogenesis and expresses an analogous gly ... | 2004 | 15367611 |
| the m2 gene product of murine gammaherpesvirus 68 is required for efficient colonization of splenic follicles but is not necessary for expansion of latently infected germinal centre b cells. | infection of mice with murine gammaherpesvirus 68 is characterized by a marked transient expansion of latently infected splenic germinal centre (gc) b cells, which is followed by lower levels of persistent infection in gc and memory b cells. virus transcription within gc b cells is restricted to a number of latency-associated open reading frames, including m2. this gene encodes a structurally unique protein of unknown function, which has been shown to be essential for the transient peak of virus ... | 2004 | 15448339 |
| pathogenetical characterization of isolate mhv-60 of mouse herpesvirus strain 68. | infection of mice with mouse herpesvirus strain 68 (mhv-68) is an excellent small animal model of gammaherpesvirus pathogenesis in a natural host. we carried out comparative studies on mhv-60, another isolate of mhv-68. the acute infection of balb/c mice inoculated intranasally (i.n.) with mhv-60 as well as its impact on tumor development were investigated. during the acute phase of infection the lungs were the main tissues infected. our results show that mhv-60 has similar pathological features ... | 2004 | 15462284 |
| inhibition of interferon-mediated antiviral activity by murine gammaherpesvirus 68 latency-associated m2 protein. | upon viral infection, the major defense mounted by the host immune system is the activation of the interferon (ifn)-mediated antiviral pathway. in order to complete their life cycle, viruses that are obligatory intracellular parasites must modulate the host ifn-mediated immune response. murine gammaherpesvirus 68 (gammahv68) infects a wide range of cell types and establishes latent infections in mice. here we demonstrate that the gammahv68 latency-associated m2 protein has a cell-type-dependent ... | 2004 | 15507628 |
| granzymes and caspase 3 play important roles in control of gammaherpesvirus latency. | gammaherpesviruses can establish lifelong latent infections in lymphoid cells of their hosts despite active antiviral immunity. identification of the immune mechanisms which regulate gammaherpesvirus latent infection is therefore essential for understanding how gammaherpesviruses persist for the lifetime of their host. recently, an individual with chronic active epstein-barr virus infection was found to have mutations in perforin, and studies using murine gammaherpesvirus 68 (gammahv68) as a sma ... | 2004 | 15507639 |
| characterization of murine gammaherpesvirus 68 glycoprotein b. | murine gammaherpesvirus 68 (mhv-68) glycoprotein b (gb) was identified in purified virions by immunoblotting, immunoprecipitation, and immunoelectron microscopy. it was synthesized as a 120-kda precursor in infected cells and cleaved into 65-kda and 55-kda disulfide-linked subunits close to the time of virion release. the n-linked glycans on the cleaved, virion gb remained partially endoglycosidase h sensitive. the processing of mhv-68 gb therefore appears similar to that of kaposi's sarcoma-ass ... | 2004 | 15542690 |
| initiation of the host response against murine gammaherpesvirus infection in immunocompetent mice. | murine gammaherpesvirus 68 (gammahv-68) provides a useful model for understanding the initiation of the host response against the gammaherpesviruses. its value as a model for such studies lies in large part with the inherent difficulties in investigating human responses against ebv and hhv-8 during the first few days following infection. while studies aimed at defining the initiation of gammahv-68 infection are far from complete, an unexpected trend in this early host response has already emerge ... | 2004 | 15671745 |
| the murine gammaherpesvirus 68 m2 gene is required for efficient reactivation from latently infected b cells. | murine gammaherpesvirus 68 (gammahv68) infection of mice provides a tractable small-animal model system for assessing the requirements for the establishment and maintenance of gammaherpesvirus latency within the lymphoid compartment. the m2 gene product of gammahv68 is a latency-associated antigen with no discernible homology to any known proteins. here we focus on the requirement for the m2 gene in splenic b-cell latency. our analyses showed the following. (i) low-dose (100 pfu) inoculation adm ... | 2005 | 15681428 |
| an optimized cd8+ t-cell response controls productive and latent gammaherpesvirus infection. | strategies to prime cd8(+) t cells against murine gammaherpesvirus 68 (gammahv68; mhv68) latency have, to date, resulted in only limited effects. while early forms of latency (<21 days) were significantly reduced, effects were not seen at later times, indicating loss of control by the primed cd8(+) t cells. in the present study, we evaluated cd8(+) t cells in an optimized system, consisting of oti t-cell-receptor (tcr) transgenic mice, which generate clonal cd8(+) t cells specific for k(b)-siinf ... | 2005 | 15681457 |
| murine gammaherpesvirus 68 rta-dependent activation of the gene 57 promoter. | the rta homolog encoded by murine gammaherpesvirus 68 (gammahv68) gene 50 is essential for virus replication and is capable of driving virus reactivation from the s11 latently infected b lymphoma cell line. here we characterize rta activation of gammahv68 gene 57, which is abundantly transcribed during the early phase of virus replication. infection of murine fibroblasts with an rta null virus demonstrated that transcription of gene 57 is dependent on rta expression. analysis of the gene 57 prom ... | 2005 | 15708602 |
| establishment and maintenance of long-term murine gammaherpesvirus 68 latency in b cells in the absence of cd40. | murine gammaherpesvirus 68 (gammahv68), like epstein-barr virus (ebv), establishes a chronic infection in its host by gaining access to the memory b-cell reservoir, where it persists undetected by the host's immune system. ebv encodes a membrane protein, lmp1, that appears to function as a constitutively active cd40 receptor, and is hypothesized to play a central role in ebv-driven differentiation of infected naive b cells to a memory b-cell phenotype. however, it has recently been shown that th ... | 2005 | 15709008 |
| murine gammaherpesvirus 68 open reading frame 11 encodes a nonessential virion component. | open reading frame 11 (orf11) is a conserved gammaherpesvirus gene that remains undefined. we identified the product of murine gammaherpesvirus 68 (mhv-68) orf11, p43, as a virion component with a predominantly perinuclear distribution in infected cells. mhv-68 lacking p43 grew normally in vitro but showed reduced lytic replication in vivo and a delay in seeding to the spleen. subsequent latency amplification was normal. thus, mhv-68 orf11 encoded a virion component that was important for in viv ... | 2005 | 15709035 |
| kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 rta reactivates murine gammaherpesvirus 68 from latency. | murine gammaherpesvirus 68 (mhv-68), kaposi's sarcoma-associated herpesvirus (hhv-8), and epstein-barr virus (ebv) are all members of the gammaherpesvirus family, characterized by their ability to establish latency in lymphocytes. the rta protein, conserved in all gammaherpesviruses, is known to play a critical role in reactivation from latency. here we report that hhv-8 rta, not ebv rta, was able to induce mhv-68 lytic viral proteins and dna replication and processing and produce viable mhv-68 ... | 2005 | 15709045 |
| transcription of the murine gammaherpesvirus 68 orf73 from promoters in the viral terminal repeats. | gammaherpesviruses persist as latent episomes in a dynamic lymphocyte pool. the regulated production of an episome maintenance protein is therefore crucial to their survival. the transcription initiation site of the murine gammaherpesvirus 68 episome maintenance protein, orf73, was mapped to the viral terminal repeats, more than 10 kb distant from the open reading frame (orf) itself. a 5' non-coding exon in the terminal repeats was spliced to the right end of the viral unique sequence, and then ... | 2005 | 15722515 |
| glycoprotein m is an essential lytic replication protein of the murine gammaherpesvirus 68. | all herpesviruses encode a homolog of glycoprotein m (gm), which appears to function in virion morphogenesis. despite its conservation, gm is inessential for the lytic replication of alphaherpesviruses. in order to address the importance of gm in gammaherpesviruses, we disrupted it in the murine gammaherpesvirus 68 (mhv-68). the mutant virus completely failed to propagate in normally permissive fibroblasts. the defective genome was rescued by either homologous recombination to restore the wild-t ... | 2005 | 15731240 |
| murine gammaherpesvirus-68 orf28 encodes a non-essential virion glycoprotein. | murine gammaherpesvirus-68 (mhv-68) orf28 is a gammaherpesvirus-specific gene of unknown function. analysis of epitope-tagged orf28 protein indicated that it was membrane-associated and incorporated into virions in n-glycosylated, o-glycosylated and unglycosylated forms. the extensive glycosylation of the small orf28 extracellular domain--most forms of the protein appeared to be mainly carbohydrate by weight--suggested that a major function of orf28 is to attach a variety of glycans to the virio ... | 2005 | 15784886 |
| murine gammaherpesvirus-68 infection of mice: a new model for human cerebral epstein-barr virus infection. | epstein-barr virus infection may cause severe neurological complications that are not mirrored by animal models. here, we show that nasal inoculation of newborn balb/c wild-type mice with mhv-68, a murine gammaherpesvirus, causes cerebral infection with inflammation in 50% of the animals. the inflammatory patterns are strikingly similar to those known from epstein-barr virus, including hydrocephalus, meningitis, cerebellitis, focal or diffuse encephalitis, and temporal lobe encephalitis. this of ... | 2005 | 15786475 |
| the murine gammaherpesvirus 68 orf27 gene product contributes to intercellular viral spread. | herpesviruses remain predominantly cell associated within their hosts, implying that they spread between cells by a mechanism distinct from free virion release. we previously identified the efficient release of murine gammaherpesvirus 68 (mhv-68) virions as a function of the viral gp150 protein. here we show that the mhv-68 orf27 gene product, gp48, contributes to the direct spread of viruses from lytically infected to uninfected cells. monoclonal antibodies to gp48 identified it on infected cel ... | 2005 | 15795291 |
| murine gammaherpesvirus 68 open reading frame 45 plays an essential role during the immediate-early phase of viral replication. | murine gammaherpesvirus 68 (mhv-68) has been developed as a model for the human gammaherpesviruses epstein-barr virus and human herpesvirus 8/kaposi's sarcoma-associated herpesvirus (hhv-8/kshv), which are associated with several types of human diseases. open reading frame 45 (orf45) is conserved among the members of the gammaherpesvirinae subfamily and has been suggested to be a virion tegument protein. the repression of orf45 expression by small interfering rnas inhibits mhv-68 viral replicati ... | 2005 | 15795297 |
| ex vivo stimulation of b cells latently infected with gammaherpesvirus 68 triggers reactivation from latency. | murine gammaherpesvirus 68 (gammahv68) infection of mice results in the establishment of a chronic infection, which is largely maintained through latent infection of b lymphocytes. acute virus replication is almost entirely cleared by 2 weeks postinfection. spontaneous reactivation of gammahv68 from latently infected splenocytes upon ex vivo culture can readily be detected at the early stages of infection (e.g., day 16). however, by 6 weeks postinfection, very little spontaneous reactivation is ... | 2005 | 15795307 |
| protein kinase c theta is not essential for t-cell-mediated clearance of murine gammaherpesvirus 68. | murine gammaherpesvirus 68 (mhv-68) is a naturally occurring rodent pathogen with significant homology to human pathogens epstein-barr virus and kaposi's sarcoma-associated herpesvirus. t cells are essential for primary clearance of mhv-68 and survival of mice following intranasal infection. previous reports have suggested that protein kinase c theta (pkctheta) is essential for t-cell activation and cytokine production in vitro. to determine the role of this molecule in vivo during the immune re ... | 2005 | 15890920 |
| murine herpesvirus pathogenesis: a model for the analysis of molecular mechanisms of human gamma herpesvirus infections. | murine herpes virus (mhv), a natural pathogen originally isolated from free-living rodents, constitutes the most amenable animal model for human gamma herpesviruses. based on dna sequence homology, this virus was classified as murid herpesvirus 4 to subfamily gammaherpesvirinae. pilot studies in our laboratory, using mice inoculated by the intranasal route, showed that mhv infects macrophages, b lymphocytes, lung alveolar as well as endothelial cells. from the lungs the virus spreads via the blo ... | 2005 | 15957234 |
| cd4 t cell control of acute and latent murine gammaherpesvirus infection requires ifngamma. | murine gammaherpesvirus 68 (gammahv68, mhv-68)-specific cd4 t cells control gammahv68 infection by reducing the frequency of latently infected cells and by inhibiting viral replication. we have previously demonstrated that cd4 t cells do not require cd8 t or b cells to control gammahv68 replication, demonstrating a helper-independent activity of cd4 t cells during gammahv68 infection. the effector mechanism(s) required for this helper-independent function of cd4 t cells and for the inhibition of ... | 2005 | 15961135 |
| role of cxcr3 in the immune response to murine gammaherpesvirus 68. | the chemokine ip-10 (cxcl10) and its cellular receptor cxcr3 are upregulated in the lung during murine gammaherpesvirus 68 (mhv-68) infection. in order to determine the role of the cxcr3 chemokine receptor in the immune response to mhv-68, cxcr3-/- mice were infected with the virus. cxcr3-/- mice showed delayed clearance of replicating mhv-68 from the lungs. this correlated with delayed t-cell recruitment to the lungs and reduced cytolytic activity prior to viral clearance. splenomegaly and the ... | 2005 | 15994833 |
| role of b-cell proliferation in the establishment of gammaherpesvirus latency. | murine gammaherpesvirus 68 (gammahv68) provides a tractable small animal model with which to study the mechanisms involved in the establishment and maintenance of latency by gammaherpesviruses. similar to the human gammaherpesvirus epstein-barr virus (ebv), gammahv68 establishes and maintains latency in the memory b-cell compartment following intranasal infection. here we have sought to determine whether, like ebv infection, gammahv68 infection in vivo is associated with b-cell proliferation dur ... | 2005 | 16014911 |
| characterization of murine gammaherpesvirus 68 v-cyclin interactions with cellular cdks. | all known gamma2-herpesviruses encode a cyclin homolog with significant homology to mammalian d-type cyclins. the murine gammaherpesvirus 68 (gammahv68) viral cyclin (v-cyclin) has been shown to be oncogenic when expression is targeted to thymocytes in transgenic mice and to be critical for virus reactivation from latency. here, we investigate the interaction of the gammahv68 v-cyclin with cellular cyclin-dependent kinases (cdks). we show that, in contrast to the kaposi's sarcoma-associated herp ... | 2005 | 16102793 |
| immune mechanisms in murine gammaherpesvirus-68 infection. | the murine gamma-herpesvirus-68 (mhv-68) is a relative of the kaposi's sarcoma-associated herpesvirus (kshv) and epstein-barr virus (ebv) that infects mice. all these gamma-herpesviruses are subject to immune control, but limit the impact of this control through immune evasion. molecular evasion mechanisms have been described in abundance. however, we can only speculate what ebv and kshv immune evasion contributes to the viral lifecycle. with mhv-68, we can analyze in vivo the contribution of im ... | 2005 | 16212523 |
| alpha/beta interferons regulate murine gammaherpesvirus latent gene expression and reactivation from latency. | alpha/beta interferon (ifn-alpha/beta) protects the host from virus infection by inhibition of lytic virus replication in infected cells and modulation of the antiviral cell-mediated immune response. to determine whether ifn-alpha/beta also modulates the virus-host interaction during latent virus infection, we infected mice lacking the ifn-alpha/beta receptor (ifn-alpha/betar(-/-)) and wild-type (wt; 129s2/svpas) mice with murine gammaherpesvirus 68 (gammahv68), a lymphotropic gamma-2-herpesviru ... | 2005 | 16254350 |
| 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 |
| murine gammaherpesvirus 68 bcl-2 homologue contributes to latency establishment in vivo. | the gammaherpesviruses are characteristically latent in lymphocytes and exploit lymphocyte proliferation to establish a large, persistent pool of latent genomes. murine gammaherpesvirus 68 (mhv-68) allows the in vivo analysis of viral genes that contribute to this and other aspects of host colonization. in this study, the mhv-68 bcl-2 homologue, m11, was disrupted either in its bh1 homology domain or upstream of its membrane-localizing c-terminal domain. each m11 mutant showed normal lytic repli ... | 2005 | 15604429 |
| on phylogenetic relationships among major lineages of the gammaherpesvirinae. | phylogenetic relationships within the subfamily gammaherpesvirinae of the family herpesviridae were investigated for three species in the genus lymphocryptovirus (or gamma1 group) and nine in the genus rhadinovirus (or gamma2 group). alignments of amino acid sequences from up to 28 genes were used to derive trees by maximum-likelihood and bayesian monte carlo markov chain methods. two problem areas were identified involving an unresolvable multifurcation for a clade within the gamma2 group, and ... | 2005 | 15659749 |
| pathogenesis of gammaherpesvirus infections. | gammaherpesviruses are members of an emerging subfamily among the herpesviridae. two genera are discriminated: (i) lymphocryptovirus, including its type species epstein-barr virus (ebv), and (ii) rhadinovirus, including viruses of interest for medicine, veterinary medicine, and biomedical research, i.e. alcelaphine herpesvirus 1, bovine herpesvirus 4, equine herpesvirus 2, human herpesvirus 8, mouse herpesvirus 68, and ovine herpesvirus 2 (ovhv-2). the perception that these viruses have a narrow ... | 2006 | 16332416 |
| gamma interferon blocks gammaherpesvirus reactivation from latency. | establishment of latent infection and reactivation from latency are critical aspects of herpesvirus infection and pathogenesis. interfering with either of these steps in the herpesvirus life cycle may offer a novel strategy for controlling herpesvirus infection and associated disease pathogenesis. prior studies show that mice deficient in gamma interferon (ifn-gamma) or the ifn-gamma receptor have elevated numbers of cells reactivating from murine gammaherpesvirus 68 (gammahv68) latency, produce ... | 2006 | 16352543 |
| a gammaherpesvirus 68 gene 50 null mutant establishes long-term latency in the lung but fails to vaccinate against a wild-type virus challenge. | the gammaherpesvirus immediate-early genes are critical regulators of virus replication and reactivation from latency. rta, encoded by gene 50, serves as the major transactivator of the lytic program and is highly conserved among all the gammaherpesviruses, including epstein-barr virus, kaposi's sarcoma-associated herpesvirus, and murine gammaherpesvirus 68 (gammahv68). introduction of a translation stop codon in gammahv68 gene 50 (gene 50.stop gammahv68) demonstrated that rta is essential for v ... | 2006 | 16415035 |
| identification of spliced gammaherpesvirus 68 lana and v-cyclin transcripts and analysis of their expression in vivo during latent infection. | regulation of orf73 (lana) gene expression is critical to the establishment and maintenance of latency following infection by members of the gamma-2 herpesvirus (rhadinovirus) family. previous studies of murine gammaherpesvirus 68 (gammahv68) have demonstrated that loss of lana function results in a complete failure to establish virus latency in the spleens of laboratory mice. here we report the characterization of alternatively spliced lana and v-cyclin (orf72) transcripts encoded by gammahv68. ... | 2006 | 16439562 |
| limited il-6 production following infection with murine gammaherpesvirus 68. | murine gammaherpesvirus 68 (gammahv-68) was found to induce il-6 secretion following in vitro infection of macrophages, but not cultured dendritic or epithelial cells. a detectable, but very limited il-6 response was observed in the lungs and mediastinal lymph nodes following intranasal infection. surprisingly, no detectable in vivo il-6 production was observed in the spleen or sera of infected mice despite observable systemic leukocytosis. these studies demonstrate that endogenous il-6 producti ... | 2006 | 16489506 |
| the m4 gene of murine gammaherpesvirus 68 modulates latent infection. | murine gammaherpesvirus 68 (mhv-68) encodes a set of unique genes, m1, m2, m3 and m4, and eight non-translated trna-like molecules that are thought to be important in virus-host interactions and latent infection. the m4 gene is predicted to encode a novel secreted protein. to investigate the role of m4 in viral pathogenesis, a mutant mhv-68 that did not express m4 was constructed and its replication was characterized in vitro and in vivo. virus replication was identical to the wild type in vitro ... | 2006 | 16528028 |
| murine gammaherpesvirus-68 glycoprotein h-glycoprotein l complex is a major target for neutralizing monoclonal antibodies. | herpesviruses characteristically persist in immune hosts as latent genomes, but to transmit infection they must reactivate and replicate lytically. the interaction between newly formed virions and pre-existing antibody is therefore likely to be a crucial determinant of viral fitness. murine gammaherpesvirus-68 (mhv-68) behaves as a natural pathogen of conventional, inbred mice and consequently allows such interactions to be analysed experimentally in a relatively realistic setting. here, monoclo ... | 2006 | 16690911 |
| activation of vav by the gammaherpesvirus m2 protein contributes to the establishment of viral latency in b lymphocytes. | gammaherpesviruses subvert eukaryotic signaling pathways to favor latent infections in their cellular reservoirs. to this end, they express proteins that regulate or replace functionally specific signaling proteins of eukaryotic cells. here we describe a new type of such viral-host interaction that is established through m2, a protein encoded by murine gammaherpesvirus 68. m2 associates with vav proteins, a family of phosphorylation-dependent rho/rac exchange factors that play critical roles in ... | 2006 | 16731951 |
| murine gammaherpesvirus (mhv) mk3 gene sequence diversity among 72, 4556, and 68 strains. | murid herpesvirus 4 (muhv-4) currently serves as a model for study of human gamma-herpesvirus pathogenesis. it codes for mk3 protein that similarly as k5 protein of kaposi's sarcoma-associated herpesvirus are members of a family of structurally related viral immune evasion molecules possessing ring-ch finger domain with ubiquitin ligase activity. murine herpesvirus 72 (mhv-72) isolated from the same species of free-living small rodent is considered as closely related to murine herpesvirus 68 (mh ... | 2006 | 16791419 |
| differential requirement for cd28 and cd80/86 pathways of costimulation in the long-term control of murine gammaherpesvirus-68. | the costimulatory molecules cd80 and cd86 (b7-1 and b7-2) are upregulated on mature antigen-presenting cells and interact with positive and negative regulators of cd8 t cell function, cd28 and cd152 (ctla4) respectively. in this study, we examined the role of cd80 and cd86 in the immune response to murine gammaherpesvirus-68 (mhv-68) using cd80/86-/- mice. as we had previously shown that cd28 (the only known activating receptor for cd80 and 86) is not essential for long-term control of mhv-68, w ... | 2006 | 16934307 |
| cd80 and cd86 control antiviral cd8+ t-cell function and immune surveillance of murine gammaherpesvirus 68. | the interactions between cd80 and cd86 on antigen-presenting cells and cd28 on t cells serve as an important costimulatory signal in the activation of t cells. although the simplistic two-signal hypothesis has been challenged in recent years by the identification of different costimulators, this classical pathway has been shown to significantly impact antiviral humoral and cellular immune responses. how the cd80/cd86-cd28 pathway affects the control of chronic or latent infections has been less ... | 2006 | 16940527 |
| orf18 is a transfactor that is essential for late gene transcription of a gammaherpesvirus. | lytic replication of the tumor-associated human gammaherpesviruses epstein-barr virus and kaposi's sarcoma-associated herpesvirus has important implications in pathogenesis and tumorigenesis. herpesvirus lytic genes have been temporally classified as exhibiting immediate-early (ie), early, and late expression kinetics. though the regulation of ie and early gene expression has been studied extensively, very little is known regarding the regulation of late gene expression. late genes, which primar ... | 2006 | 16973577 |
| evidence for cdk-dependent and cdk-independent functions of the murine gammaherpesvirus 68 v-cyclin. | gamma-2 herpesviruses encode homologues of mammalian d-type cyclins (v-cyclins), which likely function to manipulate the cell cycle, thereby providing a cellular environment conducive to virus replication and/or reactivation from latency. we have previously shown that the v-cyclin of murine gammaherpesvirus 68 is an oncogene that binds and activates cellular cyclin-dependent kinases (cdks) and is required for efficient reactivation from latency. to determine the contribution of v-cyclin-mediated ... | 2006 | 17005668 |
| the chemokine decoy receptor m3 blocks cc chemokine ligand 2 and cxc chemokine ligand 13 function in vivo. | chemokines and their receptors play a key role in immune homeostasis regulating leukocyte migration, differentiation, and function. viruses have acquired and optimized molecules that interact with the chemokine system. these virus-encoded molecules promote cell entry, facilitate dissemination of infected cells, and enable the virus to evade the immune response. one such molecule in the murine gammaherpesvirus 68 genome is the m3 gene, which encodes a secreted 44-kda protein that binds with high ... | 2006 | 17082648 |
| murine gammaherpesvirus-68 glycoprotein b presents a difficult neutralization target to monoclonal antibodies derived from infected mice. | persistent viruses disseminate from immune hosts. they must therefore resist neutralization by antibody. murine gammaherpesvirus-68 (mhv-68) represents an accessible model with which to address how resistance to neutralization is achieved and how overcoming it might improve infection control. the mhv-68 glycoprotein b (gb), like that of other herpesviruses, is a virion protein that is essential for infectivity. as such, it presents a potential neutralization target. in order to test whether viru ... | 2006 | 17098966 |
| cd4+ t cells specific for a model latency-associated antigen fail to control a gammaherpesvirus in vivo. | cd4(+) t cells play a major role in containing herpesvirus infections. however, their cellular targets remain poorly defined. in vitro cd4(+) t cells have been reported to kill b cells that harbor a latent gammaherpesvirus. we used the b cell-tropic murine gammaherpesvirus-68 (mhv-68) to test whether this also occurred in vivo. mhv-68 that expressed cytoplasmic ovalbumin (ova) in tandem with its episome maintenance protein, orf73, stimulated cd8(+) t cells specific for the h2-k(b)-restricted ova ... | 2006 | 17109468 |
| ifn-stimulated gene 15 functions as a critical antiviral molecule against influenza, herpes, and sindbis viruses. | type i interferons (ifns) play an essential role in the host response to viral infection through the induction of numerous ifn-stimulated genes (isgs), including important antiviral molecules such as pkr, rnase l, mx, and inos. yet, additional antiviral isgs likely exist. ifn-stimulated gene 15 (isg15) is a ubiquitin homolog that is rapidly up-regulated after viral infection, and it conjugates to a wide array of host proteins. although it has been hypothesized that isg15 functions as an antivira ... | 2007 | 17227866 |
| inhibition of nf-kappab activation in vivo impairs establishment of gammaherpesvirus latency. | a critical determinant in chronic gammaherpesvirus infections is the ability of these viruses to establish latency in a lymphocyte reservoir. the nuclear factor (nf)-kappab family of transcription factors represent key players in b-cell biology and are targeted by gammaherpesviruses to promote host cell survival, proliferation, and transformation. however, the role of nf-kappab signaling in the establishment of latency in vivo has not been addressed. here we report the generation and in vivo cha ... | 2007 | 17257062 |
| the dynamics of murid gammaherpesvirus 4 within wild, sympatric populations of bank voles and wood mice. | murid gammaherpesvirus 4 (muhv-4) is widely used as a small animal model for understanding gammaherpesvirus infections in man. however, there have been no epidemiological studies of the virus in wild populations of small mammals. as muhv-4 both infects cells associated with the respiratory and immune systems and attempts to evade immune control via various molecular mechanisms, infection may reduce immunocompetence with potentially serious fitness consequences for individuals. here we report a l ... | 2007 | 17347391 |
| murine gammaherpesvirus 68: a model for the study of epstein-barr virus infections and related diseases. | epstein-barr virus (ebv) is a ubiquitous human gammaherpesvirus (ghv) that causes acute infection and establishes life-long latency. ebv is associated with the development of b-cell lymphoproliferative disorders, several malignant cancers, the syndrome of infectious mononucleosis, and chronic interstitial lung disease. although the molecular biology of ebv has been characterized extensively, the associated disease conditions and their pathogenesis are difficult to study in human populations beca ... | 2007 | 17348290 |
| gamma interferon blocks gammaherpesvirus reactivation from latency in a cell type-specific manner. | gammaherpesviruses are important pathogens whose lifelong survival in the host depends critically on their capacity to establish and reactivate from latency, processes regulated by both viral genes and the host immune response. previous work has demonstrated that gamma interferon (ifn-gamma) is a key regulator of chronic infection with murine gammaherpesvirus 68 (gammahv68), a virus that establishes latent infection in b lymphocytes, macrophages, and dendritic cells. in mice deficient in ifn-gam ... | 2007 | 17360749 |
| epstein-barr virus bglf4 kinase induces premature chromosome condensation through activation of condensin and topoisomerase ii. | previous studies of epstein-barr virus (ebv) replication focused mainly on the viral and cellular factors involved in replication compartment assembly and controlling the cell cycle. however, little is known about how ebv reorganizes nuclear architecture and the chromatin territories. in ebv-positive nasopharyngeal carcinoma na cells or akata cells, we noticed that cellular chromatin becomes highly condensed upon ebv reactivation. in searching for the possible mechanisms involved, we found that ... | 2007 | 17360754 |
| the chemokine binding protein m3 prevents diabetes induced by multiple low doses of streptozotocin. | multiple injections of low-dose streptozotocin (mlds) induce lymphocytic insulitis and diabetes in rodents. to test whether the influx of inflammatory cells was associated with changes in the expression of chemokines, we measured the expression of all known chemokine ligands by real-time quantitative pcr in isolated islets. with the exception of ccl20 and ccl19, chemokines were not significantly expressed in islets from wild-type mice before mlds treatment. ten days after treatment, the expressi ... | 2007 | 17372021 |
| murine gammaherpesvirus 68 open reading frame 24 is required for late gene expression after dna replication. | open reading frame 24 (orf24) of murine gammaherpesvirus 68 (mhv-68) is conserved among beta- and gammaherpesviruses; however, its function in viral replication has not been defined. using mhv-68 as a model, we have identified orf24 as being essential for viral replication. an orf24-null virus was generated and shown to be defective in late gene expression. expression of early genes, as well as viral genome replication, was not affected. furthermore, the defect in late gene expression was likely ... | 2007 | 17392360 |
| cd8+ t cell dysfunction and increase in murine gammaherpesvirus latent viral burden in the absence of 4-1bb ligand. | studies of costimulatory receptors belonging to the tnfr family have revealed their diverse roles in affecting different stages of the t cell response. the 4-1bb ligand (4-1bbl)/4-1bb pathway has emerged as a receptor-ligand pair that impacts not the initial priming, but later phases of the t cell response, such as sustaining clonal expansion and survival, maintaining memory cd8(+) t cells, and supporting secondary expansion upon ag challenge. although the role of this costimulatory pathway in c ... | 2007 | 17404306 |
| glycosaminoglycan interactions in murine gammaherpesvirus-68 infection. | glycosaminoglycans (gags) commonly participate in herpesvirus entry. they are thought to provide a reversible attachment to cells that promotes subsequent receptor binding. murine gamma-herpesvirus-68 (mhv-68) infection of fibroblasts and epithelial cells is highly gag-dependent. this is a function of the viral gp150, in that gp150-deficient mutants are much less gag-dependent than wild-type. here we show that the major mhv-68 gag-binding protein is not gp150 but gp70, a product of orf4. surpris ... | 2007 | 17406671 |
| murine gammaherpesvirus 68 orf20 induces cell-cycle arrest in g2 by inhibiting the cdc2-cyclin b complex. | the objective of this work was to identify novel viral 'evasion' genes without homology in the database through functional assays. using this approach, the 'unassigned', conserved murine gammaherpesvirus orf20 gene was shown to localize in the nucleus and to induce cell-cycle arrest followed by apoptosis in both mouse and human cells. such growth-arrested cells did not express phospho-histone h3, demonstrating that the virus protein caused arrest at the g2 stage of the cell cycle. to characteriz ... | 2007 | 17412972 |
| serological survey of virus infection among wild house mice (mus domesticus) in the uk. | the serological prevalence of 13 murine viruses was surveyed among 103 wild-caught and 51 captive-bred house mice (mus domesticus), originating from several trapping locations in northwest england, using blood samples obtained during routine health screening of an established wild mouse colony. a high proportion of recently caught wild mice were seropositive for mouse hepatitis virus (86%), mouse cytomegalovirus (79%), mouse thymic virus (78%), mouse adenovirus (68%), mouse parvovirus (59%) and ... | 2007 | 17430622 |
| recombinant murine gammaherpesvirus 68 (mhv-68) as challenge virus to test efficacy of vaccination against chronic virus infections in the mouse model. | efficient vaccines against aids, hepatitis c and other persistent virus infections are urgently needed. vaccine development has been especially hampered by the lack of suitable small animal models to reliably test the protective capacity of candidate vaccines against such chronic viral infections. a natural mouse pathogen such as mhv-68 that persists lifelong after infection, appears to be a particularly promising candidate for a more relevant model system. here, we investigated infections with ... | 2007 | 17433507 |
| murine gammaherpesvirus 68 contains two functional lytic origins of replication. | a 1.25-kbp dna fragment from the right side of the genome containing the lytic origin of replication (orilyt) of murine gammaherpesvirus 68 (mhv-68) has been identified by a plasmid replication assay. here we show that a mutant mhv-68 with a deletion of an essential part of this orilyt, generated by using an mhv-68 bacterial artificial chromosome, was only slightly attenuated and still able to replicate but that a mutant containing an additional deletion on the left side of the genome was replic ... | 2007 | 17442722 |