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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 ...200415194758
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 ...200415194759
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 ...200415204922
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 ...200415280496
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 ...200415294989
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 ...200415308708
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 ...200415308716
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 ...200415367611
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 ...200415448339
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 ...200415462284
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 ...200415507628
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 ...200415507639
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 ...200415542690
transcriptome profile of murine gammaherpesvirus-68 lytic infection.the murine gammaherpesvirus-68 genome encodes 73 protein-coding open reading frames with extensive similarities to human gamma(2) herpesviruses, as well as unique genes and cellular homologues. we performed transcriptome analysis of stage-specific viral rna during permissive infection using an oligonucleotide-based microarray. using this approach, m4, k3, orf38, orf50, orf57 and orf73 were designated as immediate-early genes based on cycloheximide treatment. the microarray analysis also identifi ...200312533705
the wood mouse is a natural host for murid herpesvirus 4.infection of laboratory mice by the murid herpesvirus 4 (mhv-4) is a much studied model system for gammaherpesvirus pathogenesis. little, however, is known about its natural host range, epidemiology and pathogenesis outside the laboratory. we have studied mhv-4 infection in free-living murids in the uk. using a combination of serology and pcr analysis, we found that mhv-4 was endemic in wood mice (apodemus sylvaticus) but not in two species of voles (clethrionomys glareolus, microtus agrestis). ...200312533706
murine gammaherpesvirus 68 lacking thymidine kinase shows severe attenuation of lytic cycle replication in vivo but still establishes latency.the lytic cycle functions of gammaherpesviruses have received relatively little attention to date, at least in part due to the lack of a convenient experimental model. the murine gammaherpesvirus 68 (mhv-68) now provides such a model and allows the roles of individual lytic cycle gammaherpesvirus proteins to be evaluated in vivo. we have used mhv-68 to determine the contribution of a gammaherpesvirus thymidine kinase (tk) to viral lytic replication and latency establishment. mhv-68 mutants with ...200312551978
effective vaccination against long-term gammaherpesvirus latency.the fundamental question of whether a primed immune system is capable of preventing latent gammaherpesvirus infection remains unanswered. recent studies showing that vaccination can reduce acute replication and short-term latency but cannot alter long-term latency further call into question the possibility of achieving sterilizing immunity against gammaherpesviruses. using the murine gammaherpesvirus 68 (gammahv68) system, we demonstrate that it is possible to effectively vaccinate against long- ...200312551990
absence of a functional defect in cd8+ t cells during primary murine gammaherpesvirus-68 infection of i-a(b-/-) mice.the murine gammaherpesvirus-68 kills i-a(b-/-) mice despite the presence of virus-specific cd8+ cytotoxic t lymphocytes (ctl). this has raised the possibility that these ctl are functionally abnormal. here, no difference was observed between i-a(b-/-) mice and i-a(b+/+) controls in virus-specific ctl function, t cell receptor usage, or surface phenotype. thus ctl immunity was independent of cd4+ t cells in a chronic herpesvirus infection, but was still inadequate to control virus replication.200312560565
inhibition of gammaherpesvirus replication by rna interference.rna interference (rnai) is a conserved mechanism in which double-stranded, small interfering rnas (sirnas) trigger a sequence-specific gene-silencing process. here we describe the inhibition of murine herpesvirus 68 replication by sirnas targeted to sequences encoding rta, an immediate-early protein known as an initiator of the lytic viral gene expression program, and open reading frame 45 (orf 45), a conserved viral protein. our results suggest that rnai can block gammaherpesvirus replication a ...200312584354
murine gammaherpesvirus-68 infects microglia and induces high levels of pro-inflammatory cytokine production.murine gammaherpesvirus-68 (mhv-68) has been established as a tractable model for the study of human herpesvirus infections. recent associations between herpesvirus infections and inflammatory central nervous system (cns) disorders, including multiple sclerosis (ms), have prompted us to investigate the susceptibility of cultured microglia and astrocytes to mhv-68 infection. in the present study, we demonstrate that mhv-68 can infect both cell types. importantly, we show that mhv-68-infected micr ...200312620645
cloning of herpesviral genomes as bacterial artificial chromosomes.herpesviruses, which are important pathogens for both animals and humans, have large and complex genomes with a coding capacity for up to 225 open reading frames (orfs). due to the large genome size and the slow replication kinetics in vitro of some herpesviruses, mutagenesis of viral genes in the context of the viral genome by conventional recombination methods in cell culture has been difficult. given that mutagenesis of viral genes is the basic strategy to investigate function, many of the he ...200312627394
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 ...200312667789
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 ...200312719566
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 ...200312805429
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 ...200312805472
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 ...200312811845
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 ...200312857900
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 ...200312857922
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 cxcl8.200312857930
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 ...200312915582
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 ...200312966553
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 ...200312970434
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 ...200314610197
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 ...200314645566
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 ...200314645600
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 ...200314645921
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 ...200312477865
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 ...200312502858
humoral immune response and protection from viral infection in mice vaccinated with inactivated mhv-68: effects of type i interferon.infection of mice by murine gammaherpesvirus 68 (mhv-68) represents a suitable animal model in which to investigate the immune response against gammaherpesviruses and to test the efficacy of vaccination strategies. in this study, we evaluated the efficacy of heat-inactivated mhv-68 as a vaccine as well as the adjuvant activity of type i interferon (ifn-i) administered together with the vaccine. mice vaccinated with inactivated mhv-68 and subsequently infected with the virus exhibited a significa ...200212513907
disruption of the m2 gene of murine gammaherpesvirus 68 alters splenic latency following intranasal, but not intraperitoneal, inoculation.infection of mice with murine gammaherpesvirus 68 (gamma hv68; also referred to as mhv68) provides a tractable small-animal model with which to address the requirements for the establishment and maintenance of gammaherpesvirus infection in vivo. the m2 gene of gamma hv68 is a latency-associated gene that encodes a protein lacking discernible homology to any known viral or cellular proteins. m2 gene transcripts have been detected in latently infected splenocytes (s. m. husain, e. j. usherwood, h. ...200211799175
chemokine induction and leukocyte trafficking to the lungs during murine gammaherpesvirus 68 (mhv-68) infection.murine gammaherpesvirus 68 replicates in the alveolar epithelium and induces an inflammatory infiltrate in the lung, following intranasal challenge, and is cleared 10 and 13 days after infection by a t-cell-dependent mechanism. in order to understand the development of the immune response to this virus and how leukocyte trafficking to the lung is regulated, chemokine expression during mhv-68 infection was examined in lung tissue using an rnase protection assay. expression of rantes, eotaxin, mip ...200211853399
cd28(-/-) mice show defects in cellular and humoral immunity but are able to control infection with murine gammaherpesvirus 68.the role of cd28-dependent costimulatory interactions in the development and maintenance of antiviral immune responses was investigated in a mouse model of gammaherpesvirus infection. cd28(-/-) mice could clear a productive infection with murine gammaherpesvirus 68 (mhv-68), although early lung viral titers were significantly increased. both cd28(-/-) and cd28(+/+) mice maintained effective long-term control of mhv-68. gamma interferon responses appeared to develop more slowly in cd28(-/-) mice, ...200211861872
gammaherpesvirus lytic gene expression as characterized by dna array.gammaherpesviruses are associated with a number of diseases including lymphomas and other malignancies. murine gammaherpesvirus 68 (mhv-68) constitutes the most amenable animal model for this family of pathogens. however experimental characterization of gammaherpesvirus gene expression, at either the protein or rna level, lags behind that of other, better-studied alpha- and beta-herpesviruses. we have developed a cdna array to globally characterize mhv-68 gene expression profiles, thus providing ...200212021358
characterization of a spontaneous 9.5-kilobase-deletion mutant of murine gammaherpesvirus 68 reveals tissue-specific genetic requirements for latency.murine gammaherpesvirus 68 (gammahv68 [also known as mhv-68]) establishes a latent infection in mice, providing a small-animal model with which to identify host and viral factors that regulate gammaherpesvirus latency. while gammahv68 establishes a latent infection in multiple tissues, including splenocytes and peritoneal cells, the requirements for latent infection within these tissues are poorly defined. here we report the characterization of a spontaneous 9.5-kb-deletion mutant of gammahv68 t ...200212050366
a new approach to epitope confirmation by sampling effector/memory t cells migrating to the lung.the identification of t cell epitopes that elicit a weak t cell response is technically challenging due to the relatively low resolution of many available screening assays. peptide immunization can confirm the immunogenicity of a given peptide, however, this also often induces a low frequency response in lymphoid organs. in this report, we use the murine gammaherpesvirus-68 model system to describe a novel technique to enrich for antigen-experienced t cells in vivo as an aid to epitope mapping. ...200212133630
immunophenotyping of leukocytes in peripheral blood of balb/c mice infected with mouse herpesvirus isolate 72.we characterized leukocytes in peripheral blood of balb/c mice infected with mouse herpesvirus isolate 72 (mhv-72) representing an isolate of mouse herpesvirus strain 68 (mhv-68, species murid herpesvirus 4, genus rhadinovirus, subfamily gammaherpesvirinae, family herpesviridae) (van regenmortel et al., 2000). in acute infection (up to day 30 post infection (p.i.)) the number of cd8+ t cells increased, reaching a maximum at day 11 p.i. this increase correlated with that of cd4+ t, activated cd 1 ...200212197630
pathogenetic characterization of a mouse herpesvirus isolate sumava.balb/c mice inoculated intranasally (i.n.) with the mouse herpesvirus isolate sumava (mhv-sumava) did not show apparent symptoms of illness. however, they showed an increase in the number of leukocytes and appearance of atypical leukocytes in peripheral blood. the infiltration of spleen with atypical cells resulted in splenomegaly. in the course of the infection the virus persisted in lungs, spleen, thymus, bone marrow, mammary glands, peritoneal macrophages and liver. we regard mhv-sumava as on ...200212197633
elevated chemokine responses are maintained in lungs after clearance of viral infection.we observed two patterns of chemokine expression in the lungs of mice infected with murine gammaherpesvirus 68: peaks of chemokine expression correlated with or occurred after the peak of viral gene expression. chemokine expression remained elevated through 29 days postinfection.200212239330
murine gammaherpes virus as a cofactor in the development of pulmonary fibrosis in bleomycin resistant mice.studies of human tissue have suggested an association between productive epstein barr virus and idiopathic pulmonary fibrosis (ipf). however, a pathogenic role for the virus has not been established. this study was undertaken to develop an animal model, which would explore the association between viral infection and pulmonary fibrosis. balb/c mice (n=30), resistant to bleomycin, were primed with murine gammaherpesvirus 68 and then given intraperitoneal bleomycin. the mice were sacrificed at 28 d ...200212449178
regression of a murine gammaherpesvirus 68-positive b-cell lymphoma mediated by cd4 t lymphocytes.murine gammaherpesvirus 68-infected s11 cells were injected subcutaneously into nude mice. adoptively transferred restimulated lymphocytes consistently elicited the regression of s11 tumors. cd4 t lymphocytes were most effective in preventing tumor formation, and immunohistochemistry highlighted populations of cd4 t cells in regressing tumors.200111238875
virus-specific and bystander cd8+ t-cell proliferation in the acute and persistent phases of a gammaherpesvirus infection.the cycling characteristics of cd8+ t cells specific for two lytic-phase epitopes of murine gammaherpesvirus 68 (gammahv68) have been analyzed for mice with high or low levels of virus persistence. the extent of cell division is generally reflective of the antigen load and suggests that gammahv68 may be regularly reactivating from latency for some months after the resolution of the acute phase of the infectious process. although gammahv68 infection is also associated with massive proliferation o ...200111287596
characterization of the murine gammaherpesvirus 68 orf74 product: a novel oncogenic g protein-coupled receptor.murine gammaherpesvirus (mhv-68) is well established as a small animal model for the study of gammaherpesviruses. the mhv-68 genome contains an open reading frame (orf74) that has significant sequence homology with mammalian g-protein coupled receptors (gpcrs) and the gpcr from the related kaposi's sarcoma-associated herpesvirus (kshv). here we show that the mhv-68 orf74 is predicted to encode a gpcr since it has seven potential transmembrane helices and that it has other sequence motifs in comm ...200111297694
historical background.the persisting ancient view of cancer as a contagious disease ended with 19th century scientific investigations which seemed to show it was not. the resulting dogma against an infectious cause for cancer produced great prejudice in the scientific community against the first report of an oncogenic virus by rous early in the 20th century and, even in the 1950s, against gross's finding of a murine leukaemia virus and a murine virus causing solid tumours. the lucké frog renal carcinoma virus was the ...200111313002
kinetics of murine gammaherpesvirus 68 gene expression following infection of murine cells in culture and in mice.a model system to study the pathogenesis of gammaherpesvirus infections is the infection of mice with murine gammaherpesvirus 68 (mhv-68). to define the kinetics of infection, we developed an rnase protection assay to quantitate gene expression from lytic (k3, rta, m8, dna polymerase [dna pol], and gb) and candidate latency (m2, m3, m9, m11, orf73, and orf74) genes. all candidate latency genes were expressed during lytic infection of 3t3 cells. four kinetic classes of transcripts were observed f ...200111333874
analysis of a novel strain of murine gammaherpesvirus reveals a genomic locus important for acute pathogenesis.infection of mice by murine gammaherpesvirus 68 (mhv-68) is an excellent small-animal model of gammaherpesvirus pathogenesis in a natural host. we have carried out comparative studies of another herpesvirus, murine herpesvirus 76 (mhv-76), which was isolated at the same time as mhv-68 but from a different murid host, the yellow-necked mouse (apodemus flavicollis). molecular analyses revealed that the mhv-76 genome is essentially identical to that of mhv-68, except for deletion of 9,538 bp at the ...200111333912
virus reconstituted from infectious bacterial artificial chromosome (bac)-cloned murine gammaherpesvirus 68 acquires wild-type properties in vivo only after excision of bac vector sequences.we studied the in vivo biological properties of viruses reconstituted from the genome of murine gammaherpesvirus 68 (mhv-68) cloned as an infectious bacterial artificial chromosome (bac). recombinant virus rgammahv68a98.01, containing bac vector sequences, is attenuated in vivo as determined by (i) viral titers in the lungs during the acute phase of infection, (ii) the extent of splenomegaly, and (iii) the number of latently infected spleen cells reactivating virus in an ex vivo reactivation ass ...200111356978
human herpesvirus 8 envelope-associated glycoprotein b interacts with heparan sulfate-like moieties.cell-surface heparan sulfate (hs) serves as an initial attachment receptor for several herpesviruses. the gamma2-human herpesvirus-8 (hhv-8) or kaposi's sarcoma associated herpesvirus dna and transcripts have been detected in b cells, endothelial cells, macrophages, and epithelial cells. hhv-8 infects a variety of human and animal cell lines leading to latent or abortive infection. our studies showed that this broad cellular tropism may be in part due to hhv-8's interaction with the ubiquitous h ...200111384223
murine gammaherpesvirus-68 infection causes multi-organ fibrosis and alters leukocyte trafficking in interferon-gamma receptor knockout mice.murine gammaherpesvirus-68 (mhv-68) infection in interferon-gamma receptor knockout mice (ifn-gammar(-)/(-)) results in splenic fibrosis and excessive loss of splenocytes. in our present study we found that mhv-68 infection in ifn-gammar(-)/(-) mice also resulted in fibrosis and atrophy of the mediastinal lymph nodes, interstitial pulmonary fibrosis and fibrotic changes in the liver. atrophy and cellular depletion of the spleen in ifn-gammar(-)/(-) was not the result of increased cell death. the ...200111395389
perforin and fas in murine gammaherpesvirus-specific cd8(+) t cell control and morbidity.the immune system uses both virus-specific t cells and b cells to control the acute and latent phases of respiratory infection with the murine gammaherpesvirus 68 (gammahv-68). we sought to further define the important effector mechanisms for cd8(+) t cells. first, depletion of the cd4(+) t cells resulted in a failure of most animals to drive the virus into latency, although lytic virus in the lung was reduced by approximately 1000-fold from its peak. second, the absence of either perforin or fa ...200111458005
analysis of virus-specific cd4(+) t cells during long-term gammaherpesvirus infection.major histocompatibility complex class ii-mediated antigen presentation after intranasal infection with murine gammaherpesvirus 68 differs in mediastinal lymph nodes and spleen. evidence that virus-specific cd4(+) t cells were being stimulated was found as late as 6 to 8 months after infection, and cells specific for the viral gp150(67-83) and orf11(168-180) peptides were maintained as a fairly stable proportion of the total response.200111462049
a secreted chemokine binding protein encoded by murine gammaherpesvirus-68 is necessary for the establishment of a normal latent load.herpesviruses encode a variety of proteins with the potential to disrupt chemokine signaling, and hence immune organization. however, little is known of how these might function in vivo. the b cell-tropic murine gammaherpesvirus-68 (mhv-68) is related to the kaposi's sarcoma-associated herpesvirus (kshv), but whereas kshv expresses small chemokine homologues, mhv-68 encodes a broad spectrum chemokine binding protein (m3). here we have analyzed the effect on viral pathogenesis of a targeted disru ...200111489949
function of rta is essential for lytic replication of murine gammaherpesvirus 68.rta, encoded primarily by open reading frame 50, is well conserved among gammaherpesviruses. it has been shown that the rta proteins of epstein barr virus (ebv), kaposi's sarcoma-associated herpesvirus (kshv, or hhv-8), and murine gammaherpesvirus 68 (mhv-68; also referred to as gamma hv68) play an important role in viral reactivation from latency. however, the role of rta during productive de novo infection has not been characterized in gammaherpesviruses. since there are cell lines that can su ...200111533188
vaccination against murine gamma-herpesvirus infection.the gamma-herpesviruses establish life-long latency in the host and are important human pathogens. t cells play a major role in controlling the initial acute infection and subsequently maintaining the virus in a quiescent state. however, the nature of the t-cell response to gamma-herpesvirus infection and the requirements for effective vaccination are poorly understood. the recent development of a murine gamma-herpesvirus (murine herpesvirus-68 [mhv-68]) has made it possible to analyze t-cell re ...200111572633
murine gammaherpesvirus-68-induced interleukin-10 increases viral burden, but limits virus-induced splenomegaly and leukocytosis.based on its genomic sequence and its pathogenesis, murine gammaherpesvirus-68 (gammahv-68) has been established as a tractable model for the study of viral infections caused by the human gammaherpesviruses, epstein-barr virus or human herpesvirus-8. despite significant advances, the mechanisms responsible for gammahv-68-induced alterations in the protective host response, and the accompanying virus-induced leukocytosis, are not clear. in the present study, we questioned whether viral infection ...200111576228
antigen expression during murine gamma-herpesvirus infection.gammaherpesviruses (gammahv) establish a life-long latency in the host and are associated with a number of malignant human diseases. it is generally believed that t cells play a major role in controlling the initial acute infection and subsequently maintaining the virus in a quiescent state. however, the nature of the t cell response to gamma-herpesvirus infections is poorly understood. in the current report we took advantage of a mouse model of gammahv infection (murine herpesvirus-68, mhv-68) ...200111846230
disruption of the murine gammaherpesvirus 68 m1 open reading frame leads to enhanced reactivation from latency.murine gammaherpesvirus 68 (gammahv68, or mhv-68) is a genetically tractable, small animal model for the analysis of gammaherpesvirus pathogenesis. the gammahv68 genome is colinear with the genomes of other sequence gammaherpesviruses, containing large blocks of conserved genes interspersed by a number of putative genes without clear homologs in the other gammaherpesviruses. one of these putative unique genes, the m1 open reading frame (orf), exhibits sequence homology to a poxvirus serine prote ...200010644370
characterization of gammaherpesvirus 68 gene 50 transcription.gene 50 is the only immediate-early gene that appears to be conserved among the characterized gammaherpesviruses. it has recently been demonstrated for the human viruses epstein-barr virus (ebv) and kaposi's sarcoma-associated herpesvirus (kshv) that ectopic expression of the gene 50-encoded product in some latently infected cell lines can lead to the induction of virus replication, indicating that gene 50 is likely to play a pivotal role in regulating gammaherpesvirus reactivation. here we demo ...200010644377
infection of intestinal epithelial cells and development of systemic disease following gastric instillation of murine gammaherpesvirus-68.murine gammaherpesvirus-68 (gammahv-68) induces a lymphocytosis in mice and establishes a latent infection of b lymphocytes following intranasal administration in anaesthetized animals. because gammahv-68 is a gammaherpesvirus, it has been used as a model to understand the pathogenesis of epstein-barr virus (ebv) and human herpesvirus-8 (hhv-8) infections. in this study, we investigated the unlikely possibility that gammahv-68 could survive the harsh gastrointestinal environment to efficiently i ...200010644841
analysis of the virus-specific and nonspecific b cell response to a persistent b-lymphotropic gammaherpesvirus.respiratory challenge of mice with murine gammaherpesvirus 68 (gammahv68) results in acute replication in respiratory epithelial cells and persistent, latent infection of b cells and macrophages. gammahv68 elicits virus-specific ab, and also nonspecifically activates b cells to ab production through a cd4+ t cell-dependent process. the current analysis characterizes virus-specific and nonspecific ab production at the single cell level and investigates the requirements and nature of the nonspecif ...200010657630
a broad spectrum secreted chemokine binding protein encoded by a herpesvirus.chemokines are a family of small proteins that interact with seven-transmembrane domain receptors and modulate the migration of immune cells into sites of inflammation and infection. the murine gammaherpesvirus 68 m3 gene encodes a secreted 44-kd protein with no sequence similarity to known chemokine receptors. we show that m3 binds a broad range of chemokines, including cc, cxc, c, and cx(3)c chemokines, but does not bind human b cell-specific nor mouse neutrophil-specific cxc chemokines. this ...200010662803
lymphotoxin-alpha-deficient mice can clear a productive infection with murine gammaherpesvirus 68 but fail to develop splenomegaly or lymphocytosis.respiratory challenge with murine gammaherpesvirus 68 (mhv-68) leads to an acute productive infection of the lung and a persistent latent infection in b lymphocytes, epithelia, and macrophages. the virus also induces splenomegaly and an increase in the number of activated cd8 t cells in the circulation. lymphotoxin- alpha-deficient (ltalpha(-/-)) mice have no lymph nodes and have disrupted splenic architecture. surprisingly, in spite of the severe defect in secondary lymphoid tissue, ltalpha(-/- ...200010684295
rta of murine gammaherpesvirus 68 reactivates the complete lytic cycle from latency.herpesviruses are characterized as having two distinct life cycle phases: lytic replication and latency. the mechanisms of latency establishment and maintenance, as well as the switch from latency to lytic replication, are poorly understood. human gammaherpesviruses, including epstein-barr virus (ebv) and human herpesvirus-8 (hhv-8), also known as kaposi's sarcoma-associated herpesvirus (kshv), are associated with lymphoproliferative diseases and several human tumors. unfortunately, the lack of ...200010729142
antiapoptotic herpesvirus bcl-2 homologs escape caspase-mediated conversion to proapoptotic proteins.the antiapoptotic bcl-2 and bcl-x(l) proteins of mammals are converted into potent proapoptotic factors when they are cleaved by caspases, a family of apoptosis-inducing proteases (e. h.-y. cheng, d. g. kirsch, r. j. clem, r. ravi, m. b. kastan, a. bedi, k. ueno, and j. m. hardwick, science 278:1966-1968, 1997; r. j. clem, e. h.-y. cheng, c. l. karp, d. g. kirsch, k. ueno, a. takahashi, m. b. kastan, d. e. griffin, w. c. earnshaw, m. a. veliuona, and j. m. hardwick, proc. natl. acad. sci. usa 95 ...200010799576
absence of herpesvirus dna sequences in the 5t murine model of human multiple myeloma.kaposi's sarcoma-associated herpesvirus (kshv, also known as hhv-8) has been found in patients with multiple myeloma (mm) and postulated to be aetiologically associated with the development of this common plasma cell malignancy. a murine model of mm was previously established in which intravenous transfer of 5t myeloma cells into c57bl/kalwrij mice resulted in characteristic features of human mm. in the present study, we sought to identify herpesvirus dna sequences in this murine model of mm thr ...200010848833
cloning and mutagenesis of the murine gammaherpesvirus 68 genome as an infectious bacterial artificial chromosome.gammaherpesviruses cause important infections of humans, in particular in immunocompromised patients. recently, murine gammaherpesvirus 68 (mhv-68) infection of mice has been developed as a small animal model of gammaherpesvirus pathogenesis. efficient generation of mutants of mhv-68 would significantly contribute to the understanding of viral gene functions in virus-host interaction, thereby further enhancing the potential of this model. to this end, we cloned the mhv-68 genome as a bacterial a ...200010888635
murine gammaherpesvirus 68 cyclin d homologue is required for efficient reactivation from latency.murine gammaherpesvirus 68 (mhv68) is a gammaherpesvirus that was first isolated from murid rodents. mhv68 establishes a latent infection in the spleen and other lymphoid organs. several gammaherpesviruses, including herpesvirus saimiri, human herpesvirus 8, and mhv68, encode proteins with extensive homology to the d-type cyclins. to study the function of the cyclin homologue, a recombinant mhv68 has been constructed that lacks the cyclin homologue and expresses beta-galactosidase as a marker (m ...200010888640
analysis of gene expression in a human cell line stably transduced with herpesvirus saimiri.herpesvirus saimiri (hvs) is the prototype gamma-2 herpesvirus; it has significant homology to the human gammaherpesviruses kaposi's sarcoma-associated virus and epstein-barr virus and the murine gammaherpesvirus murine herpesvirus 68. hvs causes a persistent asymptomatic infection in its natural host, the squirrel monkey. both subgroups a and c possess the ability to immortalize common marmoset t lymphocytes to interleukin-2-independent proliferation. however, only subgroup c is capable of tran ...200010906186
the murine gammaherpesvirus 68 v-cyclin is a critical regulator of reactivation from latency.gamma-2 herpesviruses encode a homolog of mammalian d-type cyclins. the v-cyclin encoded by murine gammaherpesvirus 68 (gammahv68) induces cell cycle progression and is an oncogene (l. f. van dyk, j. l. hess, j. d. katz, m. jacoby, s. h. speck, and h. w. virgin iv, j. virol. 73:5110-5122, 1999). however, the role of the pro-proliferative v-cyclins in gamma-2 herpesvirus pathogenesis is not known. here we report the generation and characterization of a gammahv68 v-cyclin mutant (v-cyclin.lacz) th ...200010906198
generation of monoclonal antibodies directed against the immunogenic glycoprotein k8.1 of human herpesvirus 8.human herpesvirus 8 (hhv-8) is clearly associated with kaposi's sarcoma (ks), body cavity-based lymphomas (bcbl), and certain forms of multifocal castleman's disease (mcd). it appears to be the sexually transmissible agent involved in the development of aids-associated ks. hhv-8 genomes are invariably present in bcbl-derived cell lines where lytic replication of the virus can be induced by phorbol esters (pe). first-generation hhv-8 serological assays were based on these cell lines. more recentl ...200011001401
murine gammaherpesvirus-68 infection of and persistence in the central nervous system.murine gammaherpesvirus-68 (mhv-68) was originally isolated from a bank vole by passage through mouse brain. given its ability to replicate in mouse brain and its subsequent reisolation from trigeminal ganglia, it was originally considered to be an alphaherpesvirus. molecular studies have now firmly established mhv-68 to be a gammaherpesvirus. other gammaherpesviruses have been suggested to cause and in some cases shown to cause neurological disease. given the isolation history of mhv-68, we hav ...200011038374
a murine gammaherpesvirus.in 1976, within a project on isolation of herpesviruses from small rodents in former czechoslovakia, the mouse herpesvirus strain 68 (mhv-68) was isolated (blaskovic et al., 1980). this virus was accepted by the international committee on taxonomy of viruses (ictv) as a new, so far unassigned species (member) of the gammaherpesvirinae subfamily of the herpesviridae family (murphy et al., 1995). besides mhv-68, four more isolates (mhv-60, mhv-72, mhv-76, and mhv-78) similar to mhv-68 were obtaine ...200011155368
analysis of murine gammaherpesvirus-68 transcription during lytic and latent infection.murine gammaherpesvirus-68 (mhv-68) is a gamma2-herpesvirus that upon experimental infection of laboratory mice establishes a latent infection in b lymphocytes. to date, no virus-encoded gene products have been reported to be expressed during latent infection. in this study, viral transcription has been analysed in a persistently infected b-cell line and abundant and preferential transcription of open reading frame m3 has been identified. significantly, in situ hybridization analysis of latently ...19999934687
three distinct regions of the murine gammaherpesvirus 68 genome are transcriptionally active in latently infected mice.the program(s) of gene expression operating during murine gammaherpesvirus 68 (gammahv68) latency is undefined, as is the relationship between gammahv68 latency and latency of primate gammaherpesviruses. we used a nested reverse transcriptase pcr strategy (sensitive to approximately one copy of gammahv68 genome for each genomic region tested) to screen for the presence of viral transcripts in latently infected mice. based on the positions of known latency-associated genes in other gammaherpesvir ...19999971815
immunological control of a murine gammaherpesvirus independent of cd8+ t cells.adult thymectomized c57 bl/6j mice were depleted of t cell subsets by mab treatment either prior to, or after, respiratory challenge with murine gammaherpesvirus-68. protection against acute infection was maintained when either the cd4+ or the cd8+ t cell population was greatly diminished, whereas the concurrent removal of both t cell subsets proved invariably fatal. the same depletions had little effect on mice with established infection. the results indicate firstly that both cd4+ and cd8+ t c ...199910073710
macrophages are the major reservoir of latent murine gammaherpesvirus 68 in peritoneal cells.b cells have previously been identified as the major hematopoietic cell type harboring latent gammaherpesvirus 68 (gammahv68) (n. p. sunil-chandra, s. efstathiou, and a. a. nash, j. gen. virol. 73:3275-3279, 1992). however, we have shown that gammahv68 efficiently establishes latency in b-cell-deficient mice (k. e. weck, m. l. barkon, l. i. yoo, s. h. speck, and h. w. virgin, j. virol. 70:6775-6780, 1996), demonstrating that b cells are not required for gammahv68 latency. to understand this dich ...199910074181
quantitative analysis of the acute and long-term cd4(+) t-cell response to a persistent gammaherpesvirus.the murine gammaherpesvirus 68 (mhv-68) replicates in respiratory epithelial cells, where it establishes a persistent, latent infection limited predominantly to b lymphocytes. the virus-specific cd4(+) t-cell response in c57bl/6 mice challenged intranasally with mhv-68 is detected first in the mediastinal lymph nodes and then in the cervical lymph nodes and the spleen. the numbers of mhv-68-specific cd4(+) t cells generated in congenic mice homozygous for disruption of the beta2-microglobulin ge ...199910196325
identification and initial characterization of the murine gammaherpesvirus 68 gene m3, encoding an abundantly secreted protein.several viruses, including members of the gammaherpesvirus family, encode proteins that are secreted into the extracellular environment. we have identified an abundant 44-kda secreted protein that is present in the supernatant of fibroblasts infected with murine gammaherpesvirus 68 (gammahv68; also referred to as mhv-68) but not in that of uninfected fibroblasts. sequence analysis of the amino terminus and of internal peptides revealed that this protein is encoded by the gammahv68 m3 open readin ...199910196360
b cells regulate murine gammaherpesvirus 68 latency.the dynamics of the establishment of, and reactivation from, gammaherpesviruses latency has not been quantitatively analyzed in the natural host. gammaherpesvirus 68 (gammahv68) is a murine gammaherpesvirus genetically related to primate gammaherpesviruses that establishes a latent infection in infected mice. we used limiting dilution reactivation (frequency of cells reactivating gammahv68 in vitro) and limiting dilution pcr (frequency of cells carrying gammahv68 genome) assays to compare gammah ...199910233924
the murine gammaherpesvirus 68 v-cyclin gene is an oncogene that promotes cell cycle progression in primary lymphocytes.several gammaherpesviruses contain open reading frames encoding proteins homologous to mammalian d-type cyclins. in this study, we analyzed the expression and function of the murine gammaherpesvirus 68 (gammahv68) viral cyclin (v-cyclin). the gammahv68 v-cyclin gene was expressed in lytically infected fibroblasts as a leaky-late mrna of approximately 0.9 kb encoding a protein of approximately 25 kda. to evaluate the effect of the gammahv68 v-cyclin on cell cycle progression in primary lymphocyte ...199910233974
murine gammaherpesvirus m2 gene is latency-associated and its protein a target for cd8(+) t lymphocytes.murine gammaherpesvirus 68 (mhv-68) infection of mice is a potential model with which to address fundamental aspects of the pathobiology and host control of gammaherpesvirus latency. control of mhv-68 infection, like that of epstein-barr virus, is strongly dependent on the cellular immune system. however, the molecular biology of mhv-68 latency is largely undefined. a screen of the mhv-68 genome for potential latency-associated mrnas revealed that the region encompassing and flanking the genomic ...199910377445
lytic cycle t cell epitopes are expressed in two distinct phases during mhv-68 infection.murine herpesvirus-68 (mhv-68) is a type 2 gamma herpesvirus that productively infects alveolar epithelial cells during the acute infection and establishes long-term latency in b cells and lung epithelial cells. in c57bl/6 mice, t cells specific for lytic cycle mhv-68 epitope p56/db dominate the acute phase of the infection, whereas t cells specific for another lytic cycle epitope, p79/kb, dominate later phases of infection. to further understand this response, we analyzed the kinetics of ag pre ...199910395681
murine gammaherpesvirus 68 encodes a functional regulator of complement activation.sequence analysis of the murine gammaherpesvirus 68 (gammahv68) genome revealed an open reading frame (gene 4) which is homologous to a family of proteins known as the regulators of complement activation (rca proteins) (h. w. virgin, p. latreille, p. wamsley, k. hallsworth, k. e. weck, a. j. dal canto, and s. h. speck, j. virol. 71:5894-5904, 1997). the predicted gene 4 product has homology to other virally encoded rca homologs, as well as to the complement-regulatory proteins decay-accelerating ...199910438856
turnover of t cells in murine gammaherpesvirus 68-infected mice.respiratory challenge of c57bl/6 mice with murine gammaherpesvirus 68 induces proliferation of t lymphocytes early after infection, as evidenced by incorporation of the dna precursor bromodeoxyuridine. using pulse-chase analysis, splenic and peripheral blood activated t lymphocytes were found to continue dividing for at least a month after the initial virus challenge. the results are in accord with the idea that t cells are stimulated for a substantial time after the acute, lytic phase of virus ...199910438881
requirement for cd4+ t cells in v beta 4+cd8+ t cell activation associated with latent murine gammaherpesvirus infection.a cd8+ t cell lymphocytosis in the peripheral blood is associated with the establishment of latency following intranasal infection with murine gammaherpesvirus-68. remarkably, a large percentage of the activated cd8+ t cells of mice expressing different mhc haplotypes express v beta 4+ tcr. identification of the ligand driving the v beta 4+cd8+ t cell activation remains elusive, but there is a general correlation between v beta 4+cd8+ t cell stimulatory activity and establishment of latency in t ...199910477611
type i interferons and irf-1 play a critical role in the control of a gammaherpesvirus infection.the murine gammaherpesvirus 68 (mhv-68) is an ideal model system for the study of interactions between gammaherpesviruses and their hosts. intranasal infection of mice with mhv-68 results in replication of the virus in the lung epithelium followed by latent infection of b cells. resolution of productive mhv-68 infection depends on the adaptive immune system, but little is known about the role of innate immune mechanisms and the early interaction between the host and the virus. in this report, we ...199910497103
requirement for cd40 ligand, cd4(+) t cells, and b cells in an infectious mononucleosis-like syndrome.respiratory challenge with the murine gammaherpesvirus 68 (gammahv-68) results in productive infection of the lung, the establishment of latency in b lymphocytes and other cell types, transient splenomegaly, and prolonged clonal expansion of activated cd8(+) cd62l(lo) t cells, particularly a vbeta4(+) cd8(+) population that is found in mice with different major histocompatibility complex (mhc) haplotypes. aspects of the cd8(+)-t-cell response are substantially modified in mice that lack b cells, ...199910516078
t-cell vaccination alters the course of murine herpesvirus 68 infection and the establishment of viral latency in mice.diseases caused by gammaherpesviruses such as epstein-barr virus are a major health concern, and there is significant interest in developing vaccines against this class of viral infections. however, the requirements for effective control of gammaherpesvirus infection are only poorly understood. the recent development of the murine herpesvirus mhv-68 model provides an experimental tool to dissect the immune response to gammaherpesvirus infections. in this study, we investigated the impact of prim ...199910559297
kinetic and phenotypic changes in murine lymphocytes infected with murine gammaherpesvirus-68 in vitro.primary infection with murine gammaherpesvirus-68 (mhv-68), as with other members of the gammaherpesvirus subfamily, is characterized by a lymphoproliferative phase. mhv-68 causes acute splenomegaly and an infectious mononucleosis-like syndrome in which there is expansion of the cd8+ t cell subset. in long-term infections, mhv-68 is associated with lymphoma development. in order to elucidate the mechanisms underlying the proliferative processes, the events following infection of murine splenocyt ...199910573167
the murine gammaherpesvirus-68 m11 protein inhibits fas- and tnf-induced apoptosis.the murine gammaherpesvirus-68 (mhv-68) m11 gene encodes a protein predicted to have limited homology to the bcl-2 family of proteins. unlike most of the other viral bcl-2 homologues, which have both bh1 and bh2 domains conserved with respect to bcl-2, the m11 protein has a bh1 domain, but apparently lacks a bh2 domain. transfection of hela cells with an epitope-tagged mhv-68 m11 construct showed that the protein is predominantly located in the cytoplasm of cells. in hela cells, m11 inhibited ap ...199910573168
in vivo models for epstein-barr virus (ebv)-associated b cell lymphoproliferative disease (blpd).ebv infects b lymphocytes in vivo and establishes a life-long persistent infection in the host. the latent infection is controlled by ebv-specific mhc class 1-restricted ctl. immunosuppression reduces ctl activity, and this facilitates outgrowth of ebv+ve b cell lymphoproliferative disease (blpd). blpd are aggressive lesions with high mortality. this review presents some key facets in the development of ebv-associated blpd and in vivo studies on its pathogenesis. the animal models used to date i ...199910578121
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