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mechanisms of human cytomegalovirus persistence and latency.human cytomegalovirus (hcmv) is a ubiquitous beta-herpesvirus that causes severe disease primarily in immunosuppressed individuals. a major characteristic of hcmv with obvious clinical importance is the ability of the virus to establish lifelong infection within the host following the initial acute infection. one strategy used by hcmv to maintain itself within the host is the establishment of cellular sites of persistent infection and viral latency. recent studies have identified endothelial cel ...200212045013
recognition of a virus-encoded ligand by a natural killer cell activation receptor.natural killer (nk) cells express inhibitory and activation receptors that recognize mhc class i-like molecules on target cells. these receptors may be involved in the critical role of nk cells in controlling initial phases of certain viral infections. indeed, the ly49h nk cell activation receptor confers in vivo genetic resistance to murine cytomegalovirus (mcmv) infections, but its ligand was previously unknown. herein, we use heterologous reporter cells to demonstrate that ly49h recognizes mc ...200212060703
the human cytomegalovirus major immediate-early enhancer determines the efficiency of immediate-early gene transcription and viral replication in permissive cells at low multiplicity of infection.to determine the effect of the human cytomegalovirus (cmv) major immediate-early (mie) enhancer or promoter on the efficiency of viral replication in permissive human cells, we constructed recombinant viruses with their human mie promoter, enhancer, and promoter plus enhancer replaced with the murine cmv components. after a low multiplicity of infection (moi) (0.01 pfu/cell), recombinant human cmv with the murine cmv promoter replicated like the wild type but recombinant virus with the murine en ...200312610136
viral latency: a link between myocarditis and dilated cardiomyopathy? 200212099707
cytomegalovirus recruitment of cellular kinases to dissolve the nuclear lamina.the passage of large-sized herpesviral capsids through the nuclear lamina and the inner nuclear membrane to leave the nucleus requires a dissolution of the nuclear lamina. here, we report on the functions of m50/p35, a beta-herpesviral protein of murine cytomegalovirus. m50/p35 inserts into the inner nuclear membrane and is aggregated by a second viral protein, m53/p38, to form the capsid docking site. m50/p35 recruits the cellular protein kinase c for phosphorylation and dissolution of the nucl ...200212161659
type i interferons regulate inflammatory cell trafficking and macrophage inflammatory protein 1alpha delivery to the liver.macrophage inflammatory protein 1alpha (mip-1alpha, ccl3) is critical for liver nk cell inflammation and delivery of ifn-gamma to mediate downstream protective responses against murine cytomegalovirus (mcmv) infections. this system was used to evaluate the upstream contribution of the type 1 ifns, ifn-alpha/beta, in promotion of mip-1alpha production. mice deficient in ifn-alpha/beta functions, as a result of mutation in the receptor for these cytokines (ifn-alpha/betar(-)), were profoundly defi ...200212163451
high-frequency interferon-gamma-secreting splenocytes specific for murine cytomegalovirus immediate-early-1 (ie-1) peptide 168yphfmptnl176 are insufficient to provide complete protection from viral challenge.infection of balb/c mice with murine cytomegalovirus (mcmv) has been used extensively as a model system with which to study host mechanisms of immunity to cytomegaloviruses. in this model, the cytotoxic t-lymphocyte (ctl) response crucial for clearing infected cells is dominated by ctls specific for the mcmv nonapeptide 168yphfmptnl176 encoded by the immediate-early 1 (ie-1) gene. the intradermal injection of plasmid pcdna89 encoding ie-1 has been shown to offer some protection from viral challe ...200312683414
mechanism of host cell protection from complement in murine cytomegalovirus (cmv) infection: identification of a cmv-responsive element in the cd46 promoter region.mouse cells ubiquitously express crry, which is a functional orthologue of human decay-accelerating factor (daf; cd55) and membrane cofactor protein (mcp; cd46), and thus protects cells from homologous complement. nih3t3 cells expressed minute levels of mouse cd46 (mcd46) mrna but barely produced mcd46 protein. mcd46 message and protein levels were markedly increased during mouse cytomegalovirus (mcmv) infection. consistently, mcd46-expressing cells became resistant to mouse complement; primary- ...200212355449
memory inflation: continuous accumulation of antiviral cd8+ t cells over time.cd8+ t lymphocytes play an important role in the control of intracellular pathogens during both acute and persistent infections. this is particularly true in the case of persistent herpesviruses such as human cmv, which are typified by large virus-specific cd8+ t cell populations during viral latency. to understand the origin of these populations and the factors shaping them over time, we investigated the cd8+ t cell response after murine cmv (mcmv) infection. the kinetics of the acute response ...200312574372
murine cytomegalovirus abortively infects human dendritic cells, leading to expression and presentation of virally vectored genes.dendritic cells (dc) are potent antigen-presenting cells that play a crucial role in antigen-specific immune responses. thus, the targeting of exogenous antigens to dc has become a popular approach for cancer immunotherapy and vaccine development. in this report, we studied the interplay between murine cytomegalovirus (mcmv) and human monocyte-derived dc. the results showed that an enhanced green fluorescent protein (egfp)-encoding, replication-competent mcmv vector underwent abortive infection ...200312805417
murine cytomegalovirus retinitis during maids: susceptibility correlates with elevated intraocular levels of interleukin-4 mrna.to determine if murine cytomegalovirus (mcmv)-infected eyes of mice with murine acquired immunodeficiency syndrome (maids) that are destined to develop mcmv retinitis display elevated intraocular levels of interleukin-4 (il-4) mrna when compared with uninfected eyes of mice with maids and unmanipulated, uninfected, eyes of normal healthy mice.200312815549
genetic analyses of gene function and pathogenesis of murine cytomegalovirus by transposon-mediated mutagenesis.murine cytomegalovirus (mcmv) has a linear genome of 230 kb and encodes more than 170 genes, many of which have not been extensively studied for their functions in pathogenesis in vivo. a tn3-based transposon was constructed and used to generate mcmv mutants by disrupting viral gene targets. the functions of the mutated genes were investigated by studying the viral mutants in cultured cells and in immunocompetent balb/c and immunodeficient scid mice. a pool of mcmv mutants that contained the tra ...200212361762
a model system of primary murine hepatocytes infected by murine cytomegalovirus.in order to establish a model system of the murine hepatocyte infection by murine cytomegalovirus (mcmv), the primary cultured murine hepatocytes were obtained in a modified low-serum medium system by a non-perfusion method, and then infected by smith strain mcmv. infected hepatocytes showed characteristic cytopathic effect (cpe) at 30 h after infection, in which a large number of viral particles was found and ultrastructures were destroyed (as revealed by disappearance of bile canalicula and or ...199912840890
enhanced cytomegalovirus infection of developing brain independent of the adaptive immune system.cytomegalovirus (cmv) has been suggested as the most prevalent infectious agent causing neurological dysfunction in the developing brain; in contrast, cmv infections are rare in the adult brain. one explanation generally given for the developmental susceptibility to the virus is that the developing immune system is too immature to protect the central nervous system from viral infection, but as the immune system develops it can protect the brain. we suggest an alternate view: that developing brai ...200212163604
persisting murine cytomegalovirus can reactivate and has unique transcriptional activity in ocular tissue.cytomegalovirus (cmv) retinitis is an important ocular complication in human immunodeficiency virus-infected individuals and the leading cause of blindness in those not undergoing highly active antiretroviral therapy. murine cmv (mcmv) infection of mice has been shown to be a useful small-animal model for the study of cmv pathogenesis in the eye. the purpose of this study was to evaluate cmv persistence in ocular tissue and to determine the potential for reactivation. following subretinal inocul ...200212186900
in vitro and in vivo characterization of a murine cytomegalovirus with a mutation at open reading frame m166.we have recently generated a pool of murine cytomegalovirus (mcmv) mutants by using a tn3-based transposon mutagenesis approach. in this study, one of the mutants, rvm166, which contained the transposon sequence at open reading frame m166, was characterized both in tissue culture and in immunocompetent balb/c mice and immunodeficient scid mice. the viral mutant replicated as well as the wild-type smith strain in vitro in nih 3t3 cells, whereas the transposon insertion precluded the expression of ...200312584312
an essential role of the enhancer for murine cytomegalovirus in vivo growth and pathogenesis.the transcription of cytomegalovirus (cmv) immediate-early (ie) genes is regulated by a large and complex enhancer containing an array of binding sites for a variety of cellular transcription factors. previously, using bacterial artificial chromosome recombinants of the virus genome, it was reported that the enhancer region of murine cmv (mcmv) is dispensable but performs a key function for viral multiplication (a. angulo, m. messerle, u. h. koszinowski, and p. ghazal, j. virol. 72:8502-8509, 19 ...200312584345
ecological basis for fertility control in the house mouse (mus domesticus) using immunocontraceptive vaccines.laboratory studies confirm the potential for fertility control in the house mouse mus domesticus using mouse cytomegalovirus (mcmv) as a vector for an immunocontraceptive vaccine. this article presents an overview of key results from research in australia on enclosed and field populations of mice and the associated epidemiology of mcmv. the virus is geographically widespread in australia. it also persists in low population densities of mice, although if population densities are low for at least ...200212220162
the rat cytomegalovirus r78 g protein-coupled receptor gene is required for production of infectious virus in the spleen.the rat cytomegalovirus (rcmv) r33 and r78 genes are conserved within members of the subfamily betaherpesvirinae and encode proteins (pr33 and pr78, respectively) that show sequence similarity with g protein-coupled receptors. previously, the biological relevance of these genes was demonstrated by the finding that r33- and r78-deleted rcmv strains are severely attenuated in vivo. in addition, r78-deleted strains were found to replicate less efficiently in cell culture. to monitor of the expressi ...200312917474
molecular genetic characterization of the distal nkc recombination hotspot and putative murine cmv resistance control locus.the nk gene complex (nkc) controls murine cytomegalovirus (mcmv) immunity through cmv1-dependent natural killer (nk) cell responses. ly49h expression correlates with cmv1 phenotypes in different inbred strains, is required for mcmv resistance in c57bl/6 (b6) mice, and its interaction with the mcmv encoded m157 protein leads to nk cell-mediated destruction of virus-infected cells. however, genetic mapping studies have previously indicated that cmv1 should reside in the d6wum9-16 nkc interval, dis ...200312920489
strategies for the identification and analysis of viral immune-evasive genes--cytomegalovirus as an example.co-evolution of herpesviruses with their hosts has resulted in multiple interactions between viral genes and cellular functions. some interactions control genomic maintenance and replication in specific tissues, other affect the immune control at various stages. few immunomodulatory functions of genes can be predicted by sequence homology. the majority of genes with immunomodulatory properties only become apparent in functional assays. this chapter reviews procedures which have been used for suc ...200212224503
murine cytomegalovirus infection inhibits tumor necrosis factor alpha responses in primary macrophages.despite robust host immune responses the betaherpesvirus murine cytomegalovirus (mcmv) is able to establish lifelong infection. this capacity is due at least in part to the virus utilizing multiple immune evasion mechanisms to blunt host responses. macrophages are an important cell for mcmv infection, dissemination, and latency despite expression in the host of multiple cytokines, including tumor necrosis factor alpha (tnf-alpha), that can induce an antiviral state in macrophages or other cells. ...200312941924
dissemination of rat cytomegalovirus through infected granulocytes and monocytes in vitro and in vivo.the role of leukocytes in the in vivo dissemination of cytomegalovirus was studied in this experiment. rat cytomegalovirus (rcmv) could be transferred to rat granulocytes and monocytes by cocultivation with rcmv-infected fibroblasts in vitro. intravenous injection of purified infected granulocytes or monocytes resulted in a systemic infection in rats, indicating that our model is a powerful tool to gain further insight into cmv dissemination and the development of new antivirals.200314512575
transgenic expression of the activating natural killer receptor ly49h confers resistance to cytomegalovirus in genetically susceptible mice.natural resistance to infection with mouse cytomegalovirus (mcmv) is controlled by a dominant locus, cmv1. cmv1 is linked to the ly49 family of natural killer receptors on distal chromosome 6. while some studies localized cmv1 as distal to the ly49 gene cluster, genetic and functional analysis identified ly49h as a pivotal factor in resistance to mcmv. the role of these two independent genomic domains in mcmv resistance was evaluated by functional complementation using transgenesis of bacterial ...200312591908
loss of the perforin cytotoxic pathway predisposes mice to experimental cytomegalovirus retinitis.aids-related human cytomegalovirus (hcmv) retinitis continues to be a chronic ophthalmologic problem among human immunodeficiency virus type 1 (hiv-1)-infected patients who do not respond to highly active antiretroviral therapy. although hcmv retinitis occurs during hiv-1-induced immunosuppression, the precise effector mechanism(s) that fails during the immunopathogenesis of aids to allow onset and progression of hcmv retinal disease remains unclear. we therefore performed a series of experiment ...200312610115
fatal attraction: cytomegalovirus-encoded chemokine homologs.members of the cytomegalovirus (cmv) subfamily of betaherpesviruses infecting primates and rodents encode divergent proteins with sequence characteristics and activities of chemokines, a class of small, secreted proteins that control leukocyte migration and trafficking behavior. human cmv genes ul146 and ul147 encode proteins with sequence characteristics of cxc chemokines, whereas, murine cmv encodes a cc chemokine homolog (mck-2). human cmv ul146 encodes a neutrophil-attracting chemokine denot ...200212224512
synergy of type i interferon-a6 and interferon-b naked dna immunotherapy for cytomegalovirus infection.delivery of type i ifn transgenes by naked dna immunization can protect against cytomegalovirus infection and myocarditis. here, we investigate ifn transgene expression, antiviral efficacy, and immunomodulation of myocarditis using various treatment regimes in a mouse cmv model. in vivo expression of the ifn transgene was observed in the sera for 35 days post-dna inoculation. prophylactic ifn-a6 and ifn-b dna treatment for 14 days prior to murine cytomegalovirus (mcmv) infection was more efficac ...200212225378
experimental study of mouse cytomegalovirus infected mice.in order to investigate the human cytomegalovirus (hcmv) infection, the mouse cytomegalovirus (mcmv) infected mice were experimentally studied. 6 to 8 week old female balb/c mice with immunosuppression were selected to undergo the mcmv inoculations: intracranial inoculation and peritoneal inoculation. mcmv of the infected mice in various organs and tissues were detected by using beta-gal staining and in situ nucleic acid hybridization assay. the pathological changes were observed in he staining ...200212658822
improved detection and quantification of mouse cytomegalovirus by real-time pcr.during latent cytomegalovirus (cmv) infection, viral presence cannot be detected by plaque assay. therefore, we assessed the applicability of real-time pcr for temporal determination of virus dissemination in two different mouse strains. eight-week-old balb/c and c57bl/6j mice were infected with mouse cmv (mcmv) and sacrificed at 1, 2, 4, 6, 14 and 28 days post infection. real-time pcr was used to determine mcmv copy number in the heart, bone marrow cells, aorta and blood. in lung, liver, saliva ...200314609626
antiviral and immunomodulatory activity of the metal chelator ethylenediaminedisuccinic acid against cytomegalovirus in vitro and in vivo.antiviral activity of the metal chelator ethylenediaminedisuccinic acid (edds) was examined in vitro against human cytomegalovirus (hcmv) wild type strains and strains that are resistant against ganciclovir (gcv) and cidofovir (hpmpc). edds inhibited the replication of wild-type as well as gcv- and hpmpc-resistant strains with a 50% effective concentration of 7.4-12 microg/ml. at concentrations of 100 microg/ml edds, unlike gcv or hpmpc, suppressed hcmv-induced up-regulation of intercellular adh ...200212076762
the murine cytomegalovirus immunomodulatory gene m152 prevents recognition of infected cells by m45-specific ctl but does not alter the immunodominance of the m45-specific cd8 t cell response in vivo.although in vitro studies have shown that herpesviruses, including murine cmv (mcmv), encode genes that interfere with the mhc class i pathway, their effects on the ctl response in vivo is unclear. we identified a d(b)-restricted ctl epitope from mcmv m45 by screening an mcmv genomic library using ctl clones isolated from mice infected with mcmv lacking m152. because m152 severely inhibits ctl recognition of m45 in vitro, we questioned whether an m45-specific response would be generated in mice ...200212077265
dendritic cells under influence of mouse cytomegalovirus have a physiologic dual role: to initiate and to restrict t cell activation.the aim of this study is to analyze the dynamics of the mouse cytomegalovirus (mcmv)-dendritic cell (dc) interaction. immature and mature dcs derived from the mouse stem cell line factor-dependent cell paterson mixed potential were infected with a recombinant mcmv expressing green fluorescent protein. infection of immature dcs resulted in dc activation and virus production, both of which may contribute to viral dissemination. the infection of mature dcs was nonproductive and was restricted to im ...200312660946
major histocompatibility complex class i allele-specific cooperative and competitive interactions between immune evasion proteins of cytomegalovirus.cytomegaloviruses (cmvs) deploy a set of genes for interference with antigen presentation in the major histocompatibility complex (mhc) class i pathway. in murine cmv (mcmv), three genes were identified so far: m04/gp34, m06/gp48, and m152/gp40. while their function as immunoevasins was originally defined after their selective expression, this may not necessarily reflect their biological role during infection. the three immunoevasins might act synergistically, but they might also compete for the ...200212235213
coordinated and distinct roles for ifn-alpha beta, il-12, and il-15 regulation of nk cell responses to viral infection.nk cell cytotoxicity, ifn-gamma expression, proliferation, and accumulation are rapidly induced after murine cmv infections. under these conditions, the responses were shown to be elicited in overlapping populations. nevertheless, there were distinct signaling molecule requirements for induction of functions within the subsets. il-12/stat4 was critical for nk cell ifn-gamma expression, whereas ifn-alphabeta/stat1 were required for induction of cytotoxicity. the accumulation/survival of prolifera ...200212370359
experimental study on the prevention and treatment of murine cytomegalovirus hepatitis by using allitridin.allitridin (diallyl trisulfide), a main effective compound of allium sativum (garlic), was previously shown to inhibit the expression of immediate-early antigens and viral proliferation of human cytomegalovirus (hcmv) in vitro. here we have examined the prophylactic and therapeutic efficacy of allitridin in a non-lethal murine cytomegalovirus (mcmv) hepatitis in methylprednisolone-immunosuppressed balb/c mice. allitridin was administered at 25mg/kg per day (equal to the mean human dose) and 75 m ...200414670586
neutrality of the canonical nf-kappab-dependent pathway for human and murine cytomegalovirus transcription and replication in vitro.cytomegalovirus (cmv) is known to rapidly induce activation of nuclear factor kappab (nf-kappab) after infection of fibroblast and macrophage cells. nf-kappab response elements are present in the enhancer region of the cmv major immediate-early promoter (miep), and activity of the miep is strongly upregulated by nf-kappab in transient-transfection assays. here we investigate whether the nf-kappab-dependent pathway is required for initiating or potentiating human and murine cmv replication in vit ...200414694106
efficacy of methylenecyclopropane analogs of nucleosides against herpesvirus replication in vitro.we have reported previously that purine methylenecyclopropane analogs are potent agents against cytomegaloviruses. in an attempt to extend the activity of these compounds, the 2-amino-6-cyclopropylaminopurine analog, qyl-1064, was selected for further study by modifying the purine 6 substituent. a total of 22 analogs were tested against herpes simplex virus types 1 and 2 (hsv-1, hsv-2), varicella zoster virus (vzv), human cytomegalovirus (hcmv), murine cytomegalovirus (mcmv), epstein-barr virus ...200314714760
successful control of viruses by nk cells--a balance of opposing forces?natural killer (nk) cells play a crucial role in limiting the severity of diseases caused by a range of viruses. recent data have shown that the effector functions of nk cells can be specifically stimulated when nk cell activation receptors engage cellular major histocompatibility complex (mhc) class i-like ligands induced after infection or by specific viral gene products. however, to counter this nk cell response viruses have evolved an array of strategies to subvert efficient nk cell activati ...200212377557
recognition of infected cells by natural killer cells.under the influence of cytokines associated with innate immunity, natural killer (nk) cells rapidly become activated and migrate to sites of infection. upon contact with infected parenchyma they proliferate, release cytokines and/or kill cells harboring pathogens. multiple stimulatory and inhibitory receptors can provide the integrated signals that trigger this contact-mediated nk-cell function. recent work has begun to define the ligands for these receptors in the context of infection by certai ...200414734107
effective inhibition of k(b)- and d(b)-restricted antigen presentation in primary macrophages by murine cytomegalovirus.macrophages play an important role in murine cytomegalovirus (mcmv) infection in vivo, both in disseminating infection and in harboring latent virus. mcmv encodes three immune evasion genes (m4, m6, and m152) that interfere with the ability of cytotoxic t cells (ctl) to detect virus-infected fibroblasts, but the efficacy of immune evasion in macrophages has been controversial. here we show that mcmv immune evasion genes function in h-2(b) primary bone marrow macrophages (bmmphi) in the same way ...200312477835
genetic control of innate immune responses against cytomegalovirus: mcmv meets its match. 200212486611
therapeutic effects of il-12 combined with benzoylmesaconine, a non-toxic aconitine-hydrolysate, against herpes simplex virus type 1 infection in mice following thermal injury.il-12 is an inducer of type 1 t cell responses, which are essential in host defense against herpes simplex virus type 1 (hsv-1) infection. however, type 1 t cell responses are not elicited by il-12 in thermally injured mice (ti-mice) that routinely have a predominance of burn-associated type 2 t cell responses. in our previous studies, benzoylmesaconine (ben, an aconitine derivative extracted from heated-aconiti tuber) induced the generation of cd4+ t cells antagonistic to type 2 t cells (ben-cd ...200312543043
nkg2d-mediated natural killer cell protection against cytomegalovirus is impaired by viral gp40 modulation of retinoic acid early inducible 1 gene molecules.natural killer (nk) cells play a critical role in the innate immune response against cytomegalovirus (cmv) infections. although cmv encodes several gene products committed to evasion of adaptive immunity, viral modulation of nk cell activity is only beginning to be appreciated. a previous study demonstrated that the mouse cmv m152-encoded gp40 glycoprotein diminished expression of ligands for the activating nk cell receptor nkg2d on the surface of virus-infected cells. here we have defined the p ...200312756263
murine cytomegalovirus with a transposon insertional mutation at open reading frame m35 is defective in growth in vivo.we had previously constructed a pool of murine cytomegalovirus (mcmv) mutants that contained a tn3-based transposon sequence randomly inserted in the viral genome. in the study reported here, one of the mutants, rvm35, which contains the transposon insertion at open reading frame m35, was characterized both in vitro in tissue cultures and in immunocompetent balb/c and immunodeficient scid mice. our results provide the first direct evidence to suggest that m35 is not essential for viral replicati ...200312829814
cytomegalovirus m43 gene modulates t helper cell response.role of viral genes in modulating t helper 1 (th1) and t helper 2 (th2) balance is of principal interest in the study of cytomegalovirus (cmv) immunity. murine cmv (mcmv) mutants were used to explore a possible mechanism for the ability of virus to induce a predominant th1 response and to suppress th2 response by examining the production of th1 (ifn-gamma, il-2) and th2 (il-4, il-10) cytokines by the splenocytes of mice infected with wild type (wt) and mcmv mutants. results (n=6) show that as co ...200312853158
assessment of contraceptive vaccines based on recombinant mouse sperm protein ph20.mouse ph20 (mph20), the mouse homologue to guinea pig hyaluronidase protein ph20 (gpph20), was used to produce contraceptive vaccines that target both sexes of mice. previously, immunization with a female gamete antigen (the zona pellucida subunit 3 protein) delivered in a recombinant murine cytomegalovirus (mcmv), or as a purified recombinant protein, has been shown to induce infertility in female mice. there is evidence, however, that sperm protein antigens could provide broader contraceptive ...200415016952
specific recognition of virus-infected cells by paired nk receptors.nk cells show cytotoxicity and cytokine production upon recognition of virus-infected cells and play an important role in conferring protective immunity against virus infection. patients who lack functional nk cells are susceptible to severe infectious diseases such as herpesvirus infection. in addition, when nk cells are removed from cytomegalovirus-resistant mice, the virus titre after infection is markedly increased and the mice are likely to die due to infection. however, the exact mechanism ...200415027001
mutational analysis of the r33-encoded g protein-coupled receptor of rat cytomegalovirus: identification of amino acid residues critical for cellular localization and ligand-independent signalling.the rat cytomegalovirus (rcmv) r33 gene encodes a g protein-coupled receptor (gpcr), pr33, which possesses agonist-independent, constitutive signalling activity. to characterize this activity further, we generated a series of point and deletion mutants of pr33. both expression of and signalling by the mutants was evaluated. several point mutants were generated that contained modifications in the nry motif. this motif, at aa 130-132 of pr33, is the counterpart of the common dry motif of gpcrs, wh ...200415039532
activation of murine cytomegalovirus immediate-early promoter in mouse brain after transplantation of the neural stem cells.cytomegalovirus (cmv) is the most significant infectious cause of congenital infection and fatal diseases in immunocompromised patients. we have previously described a transgenic mouse model of the murine cmv (mcmv) immediate-early (ie) gene promoter fused with the lacz reporter gene (mcmv-ie-pro1) for the analysis of spatiotemporal changes of the promoter activity during brain development. since expression of the ie genes play a pivotal role in latency and reactivation, we transplanted the tran ...200415042384
vaccination of mice with bacteria carrying a cloned herpesvirus genome reconstituted in vivo.bacterial delivery systems are gaining increasing interest as potential vaccination vectors to deliver either proteins or nucleic acids for gene expression in the recipient. bacterial delivery systems for gene expression in vivo usually contain small multicopy plasmids. we have shown before that bacteria containing a herpesvirus bacterial artificial chromosome (bac) can reconstitute the virus replication cycle after cocultivation with fibroblasts in vitro. in this study we addressed the question ...200312857893
the ribonucleotide reductase r1 homolog of murine cytomegalovirus is not a functional enzyme subunit but is required for pathogenesis.ribonucleotide reductase (rnr) is the key enzyme in the biosynthesis of deoxyribonucleotides. alpha- and gammaherpesviruses express a functional enzyme, since they code for both the r1 and the r2 subunits. by contrast, betaherpesviruses contain an open reading frame (orf) with homology to r1, but an orf for r2 is absent, suggesting that they do not express a functional rnr. the m45 protein of murine cytomegalovirus (mcmv) exhibits the sequence features of a class ia rnr r1 subunit but lacks cert ...200415047841
does toll-like receptor 3 play a biological role in virus infections?the toll-like receptor (tlr) family functions to recognize conserved microbial and viral structures with the purpose of activating signal pathways to instigate immune responses against infections by these organisms. for example, in vitro studies reveal that the tlr3 ligand is a double-stranded rna (dsrna), a product of viral infections. from this observation, it has been proposed that tlr3 is likely an important first signal for virus infections. we approached this issue by investigating the rol ...200415110521
neuron-specific activation of murine cytomegalovirus early gene e1 promoter in transgenic mice.the brain is the main target in congenital cytomegalovirus (cmv) infection and immunocompromised patients. no definite evidence that a cmv has special affinity for the central nervous system (cns) has been published. here, we generated transgenic mice with an e1 promoter/enhancer region connected to the reporter gene lacz. surprisingly, expression of the transgene was completely restricted to the cns in all lines of transgenic mice. the transgene was expressed in subpopulation of neurons in the ...200312875983
diabetogenic potential of human pathogens uncovered in experimentally permissive beta-cells.pancreatic beta-cell antiviral defense plays a critical role in protection from coxsackievirus b4 (cvb4)-induced diabetes. in the present study, we tested the hypothesis that interferon (ifn)-induced antiviral defense determines beta-cell survival after infection by the human pathogen cvb3, cytomegalovirus (cmv), and lymphocytic choriomeningitis virus (lcmv). we demonstrated that mice harboring beta-cells that do not respond to ifn because of the expression of the suppressor of cytokine signalin ...200312882919
cytokine expression in murine cytomegalovirus-induced myocarditis: modulation with interferon-alpha therapy.cytomegalovirus-induced myocarditis is largely immune-mediated. balb/c mice produced higher levels of il-4 in the heart indicative of a th2-like response. although il-6, il-10, il-18, and tnf-alpha were produced in the heart during acute infection, balb/c mice lacked a substantial il-2 and ifn-gamma response. conversely, c57bl/6 mice produced significant levels of ifn-gamma in the heart with no significant levels of il-4 or il-6, suggestive of a dominant th1-like response to virus infection. ifn ...200312914761
hpmpc therapy of mcmv-induced retinal disease in the scid mouse measured by electroretinography, a non-invasive technique.the purpose of these studies was to investigate the use of non-invasive electroretinography for the evaluation of retinal disease and its treatment in an ocular murine cytomegalovirus (mcmv) disease model. while under anesthesia, 10(2.6)plaque forming units (pfu) of salivary gland passaged, smith strain mcmv was injected in the anterior chamber of 6- to 8-week-old severe combined immunodeficiency (scid) mice. at various times post-inoculation, bright-flash scotopic electroretinogram, viral titer ...200312927309
the r131 gene of rat cytomegalovirus encodes a proinflammatory cc chemokine homolog which is essential for the production of infectious virus in the salivary glands.rat cytomegalovirus (rcmv) possesses two adjacent genes, r131 and r129, which have the potential to encode cc chemokine homologs. interestingly, the amino acid sequences encoded by both genes show similarity to the sequence of the murine cmv (mcmv) mck-2 protein, which is encoded by the m131/129 gene. in order to study the significance of the r131 gene in the pathogenesis of rcmv infection, we generated two different virus strains in which the r131 open reading frame is disrupted. replication of ...200415215683
murine cytomegalovirus m41 open reading frame encodes a golgi-localized antiapoptotic protein.viruses have evolved various strategies to prevent premature apoptosis of infected host cells. some of the viral genes mediating antiapoptotic functions have been identified by their homology to cellular genes, but others are structurally unrelated to genes of known function. in this study, we used a random, unbiased approach to identify such genes in the murine cytomegalovirus genome. from a library of random transposon insertion mutants, a mutant virus that caused premature cell death was isol ...200314557649
comprehensive mutational analysis of a herpesvirus gene in the viral genome context reveals a region essential for virus replication.essential viral proteins perform vital functions during morphogenesis via a complex interaction with other viral and cellular gene products. here, we present a novel approach to comprehensive mutagenesis of essential cytomegalovirus genes and biological analysis in the 230-kbp-genome context. a random tn7-based mutagenesis procedure at the single-gene level was combined with site-specific recombination via the flp/flp recognition target site system for viral genome reconstitution. we show the fu ...200415254174
a survival game of hide and seek: cytomegaloviruses and mhc class i antigen presentation pathways.cytomegaloviruses (cmv) are members of the ubiquitous family of herpesviruses, which escape immunological clearance and persist throughout life in the infected host. cytomegaloviruses have developed numerous strategies that permit them to co-exist with their host even as an anti-virus immune response endangers their long-term survival. a considerable number of these strategies are aimed at mhc class i presentation of viral proteins to cd8+ t cells (tcd8+ ). although the gamut of cmv immune evasi ...200314583141
calling in the troops: regulation of inflammatory cell trafficking through innate cytokine/chemokine networks.the recruitment of immune effector cells to localized sites of infection is crucial for the effective delivery of innate immune mechanisms. under the conditions of infections with murine cytomegalovirus (mcmv), a herpesvirus with pathogenic potential, early immune functions are essential in the control of virus replication and virus-induced pathology. our studies have demonstrated that the chemokine macrophage inflammatory protein-1alpha (mip-1alpha) is critical for natural killer (nk) cell infl ...200314583145
reevaluation of human cytomegalovirus coding potential.the bio-dictionary-based gene finder was used to reassess the coding potential of the ad169 laboratory strain of human cytomegalovirus and sequences in the toledo strain that are missing in the laboratory strain of the virus. the gene-finder algorithm assesses the potential of an orf to encode a protein based on matches to a database of amino acid patterns derived from a large collection of proteins. the algorithm was used to score all human cytomegalovirus orfs with the potential to encode poly ...200314593199
murine cytomegalovirus m157 mutation and variation leads to immune evasion of natural killer cells.effective natural killer (nk) cell recognition of murine cytomegalovirus (mcmv)-infected cells depends on binding of the ly49h nk cell activation receptor to the m157 viral glycoprotein. here we addressed the immunological consequences of variation in m157 sequence and function. we found that most strains of mcmv possess forms of m157 that evade ly49h-dependent nk cell activation. importantly, repeated passage of mcmv through resistant ly49h+ mice resulted in the rapid emergence of m157 mutants ...200314597723
reduced expression of gamma interferon in serum and marked lymphoid depletion induced by porphyromonas gingivalis increase murine morbidity and mortality due to cytomegalovirus infection.porphyromonas gingivalis, a gram-negative anaerobe, is a major etiological agent of severe forms of periodontal disease. although periodontal disease is considered a localized disease, accumulating evidence indicates that it may lead to a predisposition to a decline in immunocompetence. human cytomegalovirus (cmv) commonly infects all human populations without producing significant clinical symptoms. immunocompromised patients usually develop a primary or reactivated cmv infection, which is asso ...200415385479
murine cytomegalovirus paralyzes macrophages by blocking ifn gamma-induced promoter assembly.macrophages (m phi) are activated by ifn gamma and are important cellular targets for infection by human and murine cytomegalovirus (mcmv), making it advantageous for cmvs to block ifn gamma-induced m phi differentiation. we found that mcmv infection inhibited ifn gamma regulation of many genes in m phi. mcmv infection blocked ifn gamma responses at the level of transcription without blocking janus kinase/signal transducer and activator of transcription pathway activation and targeted ifn respon ...200314614150
allogeneic t cells treated with amotosalen prevent lethal cytomegalovirus disease without producing graft-versus-host disease following bone marrow transplantation.infusion of donor antiviral t cells can provide protective immunity for recipients of hemopoietic progenitor cell transplants, but may cause graft-vs-host disease (gvhd). current methods of separating antiviral t cells from the alloreactive t cells that produce gvhd are neither routine nor rapid. in a model of lethal murine cmv (mcmv) infection following mhc-mismatched bone marrow transplantation, infusion of mcmv-immune donor lymphocytes pretreated with the dna cross-linking compound amotosalen ...200314634114
differential function and expression of the viral inhibitor of caspase 8-induced apoptosis (vica) and the viral mitochondria-localized inhibitor of apoptosis (vmia) cell death suppressors conserved in primate and rodent cytomegaloviruses.human cytomegalovirus (cmv) genes ul36 and ul37 encode viral inhibitor of caspase-8-induced apoptosis (vica) and viral mitochondria inhibitor of apoptosis (vmia), respectively. rhesus macaque cmv homologues, denoted rh-vica and rh-vmia, were identified and found to suppress apoptosis. one of these functions was conserved in mcmv, encoded by the m36 gene and denoted m-vica. conserved regions were compared to domains important to vica- and vmia-mediated cell death suppression. the conserved sequen ...200314644605
characterization of a novel rat cytomegalovirus (rcmv) infecting placenta-uterus of rattus rattus diardii.a new rat cytomegalovirus (rcmv) isolated from the placenta/uterus of a house rat (rattus rattus diardii) was found to productively infect rat embryo fibroblast (ref) cells. the virus produced typical herpesvirus-like cytopathic effects characterized by a lytic infection. the well-known herpesvirus morphology was confirmed by electron microscopy. its slow growth in cell culture indicated that the virus is belonging to subfamily betaherpesvirinae. electron microscopy techniques and immunohistoche ...200314648291
aids-related cytomegalovirus retinitis: lessons from the laboratory. 200415512956
susceptibility to murine cytomegalovirus retinitis during progression of maids: correlation with intraocular levels of tumor necrosis factor-alpha and interferon-gamma.to correlate tumor necrosis factor-alpha (tnf-alpha) and interferon-gamma (ifn-gamma) synthesis with histopathologic disease and virus replication within murine cytomegalovirus (mcmv)-infected eyes during progression of murine acquired immunodeficiency syndrome (maids).200415512964
dendritic cell responses to early murine cytomegalovirus infection: subset functional specialization and differential regulation by interferon alpha/beta.differentiation of dendritic cells (dcs) into particular subsets may act to shape innate and adaptive immune responses, but little is known about how this occurs during infections. plasmacytoid dendritic cells (pdcs) are major producers of interferon (ifn)-alpha/beta in response to many viruses. here, the functions of these and other splenic dc subsets are further analyzed after in vivo infection with murine cytomegalovirus (mcmv). viral challenge induced pdc maturation, their production of high ...200312682109
critical role for the oct-2/oca-b partnership in ig-secreting cells.b and t lymphocytes arise from a common precursor in the bone marrow, but ultimately acquire very different functions. the difference in function is largely attributable to the expression of tissue-specific transcription factors that activate discrete sets of genes. in previous studies we and others have shown that the specialized genes expressed by ig-secreting cells cease transcription when these cells are fused to a t lymphoma. the extinguished genes include those encoding ig, j chain, and th ...200314662861
identification of a monoclonal antibody from peromyscus maniculatus (deer mouse) cytomegalovirus (pcmv) which binds to a protein with homology to the human cmv matrix protein hcmv pp71.in this study we identified and characterized a monoclonal antibody against the matrix protein of a cytomegalovirus isolated from the common deer mouse (peromyscus maniculatus) (pcmv). the monoclonal antibody was isolated using previously described technology which could be applied to the production of monoclonal antibodies against zoonotic disease. the antibody was found to react with a protein homologous to the human cytomegalovirus (hcmv) matrix protein (pp71), the product of the ul82 open re ...200515582693
systemic immune deficiency necessary for cytomegalovirus invasion of the mature brain.cytomegalovirus (cmv) is a significant opportunistic pathogen associated with aids and immunosuppressive therapy. infection of the mature central nervous system (cns) can cause significant pathology with associated neurological deficits, mental disorders, and cognitive impairment and may have potentially fatal consequences. using genetically immunocompromised mice, we studied mechanisms of cmv invasion into, and behavior within, the cns. adult immunodeficient (nude and scid) and control mice wer ...200414722303
plasticity of t cell memory responses to viruses.virus-specific memory t cell populations demonstrate plasticity in antigenic and functional phenotype, in recognition of antigen, and in their ability to accommodate new memory t cell populations. the adaptability of complex antigen-specific t cell repertoires allows the host to respond to a diverse array of pathogens and accommodate memory pools to many pathogens in a finite immune system. this is in part accounted for by crossreactive memory t cells, which can be employed in immune responses a ...200414738760
role of murine cytomegalovirus us22 gene family members in replication in macrophages.the large cytomegalovirus (cmv) us22 gene family, found in all betaherpesviruses, comprises 12 members in both human cytomegalovirus (hcmv) and murine cytomegalovirus (mcmv). conserved sequence motifs suggested a common ancestry and related functions for these gene products. two members of this family, m140 and m141, were recently shown to affect mcmv replication on macrophages. to test the role of all us22 members in cell tropism, we analyzed the growth properties in different cell types of mcm ...200312719548
role for tumor necrosis factor alpha in murine cytomegalovirus transcriptional reactivation in latently infected lungs.interstitial pneumonia is a major clinical manifestation of primary or recurrent cytomegalovirus (cmv) infection in immunocompromised recipients of a bone marrow transplant. in a murine model, lungs were identified as a prominent site of cmv latency and recurrence. pulmonary latency of murine cmv is characterized by high viral genome burden and a low incidence of variegated immediate-early (ie) gene expression, reflecting a sporadic activity of the major ie promoters (mieps) and enhancer. the en ...200515596827
expansion of protective cd8+ t-cell responses driven by recombinant cytomegaloviruses.cd8(+) t cells are critical for the control of many persistent viral infections, such as human immunodeficiency virus, hepatitis c virus, epstein-barr virus, and cytomegalovirus (cmv). in most infections, large cd8(+)-t-cell populations are induced early but then contract and are maintained thereafter at lower levels. in contrast, cd8(+) t cells specific for murine cmv (mcmv) have been shown to gradually accumulate after resolution of primary infection. this unique behavior is restricted to cert ...200414963122
natural killer cells utilize both perforin and gamma interferon to regulate murine cytomegalovirus infection in the spleen and liver.natural killer (nk) cells are critical for innate regulation of the acute phase of murine cytomegalovirus (mcmv) infection and have been reported to utilize perforin (pfp)- and gamma interferon (ifn-gamma)-dependent effector mechanisms in an organ-specific manner to regulate mcmv infection in the spleen and liver. in this study, we further examined the roles of nk cells, pfp, and ifn-gamma in innate immunity to mcmv infection. with the recently described nk cell-deficient (nkd) mouse, we confirm ...200515596864
coordinate expression of cytokines and chemokines by nk cells during murine cytomegalovirus infection.cytokines and chemokines activate and direct effector cells during infection. we previously identified a functional group of five cytokines and chemokines, namely, ifn-gamma, activation-induced t cell-derived and chemokine-related cytokine/lymphotactin, macrophage-inflammatory protein 1alpha, macrophage-inflammatory protein 1beta, and rantes, coexpressed in individual activated nk cells, cd8(+) t cells, and cd4(+) th1 cells in vitro and during in vivo infections. however, the stimuli during infe ...200414978118
characterization of an interleukin-6- and adrenocorticotropin-dependent, immune-to-adrenal pathway during viral infection.there has been longstanding interest in the capacity of the immune system to access immunomodulatory glucocorticoid responses without invoking upstream neuroendocrine secretagogues, including crh and acth. here, we investigate the role of crh and acth in adrenal glucocorticoid responses to murine cytomegalovirus (mcmv). mice infected with mcmv exhibit il-6-dependent glucocorticoid responses that peak at 36 h post infection and protect against cytokine (tnfalpha)-mediated lethality. acute adminis ...200415044377
murine cytomegalovirus interference with antigen presentation has little effect on the size or the effector memory phenotype of the cd8 t cell response.as with most herpesviruses, cmvs encode viral genes that inhibit ag presentation to cd8 t cells (viprs). vipr function has been assumed to be essential for cmv to establish its characteristic lifetime infection of its host. we compared infection of c57bl/6 mice with wild-type murine cmv (mcmv) and a virus lacking each of mcmv's three known viprs: m4, m6, and m152. during acute infection, there was very little difference between the two viruses with respect to the kinetics of viral replication an ...200415153514
escape of mutant double-stranded dna virus from innate immune control.as innate immune system components, natural killer (nk) cells respond rapidly to infections and effectively control replication of pathogens, including murine cytomegalovirus (mcmv), a double-stranded dna beta-herpesvirus. in the absence of nk cell control, mcmv infection results in early mortality due to uncontrolled viral replication. however, here we show that even in the face of initial nk cell control, there is late recrudescence of disease and mortality in immunodeficient mice due to the o ...200415189739
murine cytomegalovirus with a transposon insertional mutation at open reading frame m155 is deficient in growth and virulence in mice.a pool of murine cytomegalovirus (mcmv) mutants was previously generated by using a tn3-based transposon mutagenesis approach (x. zhan, m. lee, j. xiao, and f. liu, j. virol. 74:7411-7421, 2000). in this study, one of the mcmv mutants, rvm155, which contained the transposon insertion in open reading frame m155, was characterized in vitro for its replication in tissue culture and in vivo for its growth and virulence in immunodeficient scid mice. compared to the wild-type strain and a rescued viru ...200415194765
use of a murine cytomegalovirus k181-derived bacterial artificial chromosome as a vaccine vector for immunocontraception.cytomegaloviruses (cmvs) are members of the betaherpesvirinae subfamily of the herpesviridae, and their properties of latency, large dna size, gene redundancy, and ability to be cloned as bacterial artificial chromosomes (bacs) suggest their utility as vaccine vectors. while the k181 strain of murine cmv (mcmv) is widely used to study mcmv biology, a bac clone of this virus had not previously been produced. we report here the construction of a bac clone of the k181(perth) strain of mcmv. the in ...200515709020
expansion and contraction of the nk cell compartment in response to murine cytomegalovirus infection.nk cells are capable of responding quickly to infectious challenge and contribute to the early defense against a wide variety of pathogens. although the innate nk cell response to murine cmv (mcmv) has been extensively characterized, its resolution and the fate of the activated nk cell population remains unexplored. herein, we characterize both the expansion and contraction phases of the nk cell response to mcmv. we demonstrate that nk cell recruitment into the immune response to mcmv infection ...200415210783
nasal peptide vaccination elicits cd8 responses and reduces viral burden after challenge with virulent murine cytomegalovirus.infection of balb/c mice with murine cytomegalovirus (mcmv) leads to cd8 cell responses to an immunodominant epitope yphfmptnl. we presented this epitope as a nasal peptide vaccine in combination with cholera toxin adjuvant, and evaluated immune responses and protection from mcmv challenge. vaccination of naive mice generated elevated numbers of peptide-specific interferon-gamma-secreting splenocytes (median 80/million, range 60 to 490), compared to control mice (median 2/million, range -4.5 to ...200515722596
cytomegalovirus infection aggravates atherogenesis in apoe knockout mice by both local and systemic immune activation.since the 1970s, cytomegalovirus (cmv) infection has been associated with atherosclerotic disease. however, the exact contribution of the virus remains uncertain. in this article we describe both a direct and indirect immune-mediated effect of the virus on the disease process. eight-week-old apolipoprotein e (apoe) knockout mice were infected with mouse cmv (mcmv) or mock injected, and they were sacrificed at 2 and 20 weeks post-injection (p.i.) to study atherosclerosis, vascular wall ifngamma a ...200414738889
a cytomegalovirus inhibitor of gamma interferon signaling controls immunoproteasome induction.both human and mouse cytomegaloviruses (hcmv and mcmv) avoid peptide presentation through the major histocompatibility complex (mhc) class i pathway to cd8(+) t cells. within the mhc class i pathway, the vast majority of antigenic peptides are generated by the proteasome system, a multicatalytic protease complex consisting of constitutive subunits, three of which can be replaced by enzymatically active gamma interferon (ifn-gamma)-inducible subunits, i.e., lmp2, lmp7, and mecl1, to form the so-c ...200414747547
hepatic dendritic cell subsets in the mouse.the cd11c(+) cell population in the non-parenchymal cell population of the mouse liver contains dendritic cells (dc), nk cells, b cells and t cells. in the hepatic cd11c(+) dc population from immunocompetent or immunodeficient [recombinase-activating gene-1 (rag1)(-/-)] c57bl/6 mice (rigorously depleted of t cells, b cells and nk cells), we identified a b220(+) cd11c(int) subset of 'plasmacytoid' dc, and a b220(-) cd11c(+) dc subset. the latter dc population could be subdivided into a major, imm ...200414768040
gain of virulence caused by loss of a gene in murine cytomegalovirus.mouse strains are either resistant or susceptible to murine cytomegalovirus (mcmv). resistance is determined by the cmv1(r) (ly49h) gene, which encodes the ly49h nk cell activation receptor. the protein encoded by the m157 gene of mcmv has been defined as a ligand for ly49h. to find out whether the m157 protein is the only ly49h ligand encoded by mcmv, we constructed the m157 deletion mutant and a revertant virus. viruses were tested for susceptibility to nk cell control in ly49h+ and ly49h- mou ...200415220428
interleukin-6 access to the axis. 200415265824
tlr9-dependent recognition of mcmv by ipc and dc generates coordinated cytokine responses that activate antiviral nk cell function.natural interferon-producing cells (ipc) respond to viruses by secreting type i interferon (ifn) and interleukin-12 (il-12). toll-like receptor (tlr) 9 mediates ipc recognition of some of these viruses in vitro. however, whether tlr9-induced activation of ipc is necessary for an effective antiviral response in vivo is not clear. here, we demonstrate that ipc and dendritic cells (dc) recognize murine cytomegalovirus (mcmv) through tlr9. tlr9-mediated cytokine secretion promotes viral clearance by ...200415345224
a novel checkpoint in the bcl-2-regulated apoptotic pathway revealed by murine cytomegalovirus infection of dendritic cells.infection with murine cytomegalovirus (mcmv) has contributed to understanding many aspects of human infection and, additionally, has provided important insight to understanding complex cellular responses. dendritic cells (dcs) are a major target for mcmv infection. here, we analyze the effects of mcmv infection on dc viability, and show that infected dcs become resistant to apoptosis induced by growth factor deprivation. the precise contribution of changes in the expression of bcl-2 family prote ...200415353550
murine cytomegalovirus infection directs macrophage differentiation into a pro-inflammatory immune phenotype: implications for atherogenesis.we have previously demonstrated that mouse cytomegalovirus (mcmv) aggravates atherosclerosis in apolipoprotein e knockout (apoe(-/-)) mice, most likely by enhancing both systemic and local (e.g. in the vascular wall) cytokine production. however, until now it was unclear which cell type is responsible for this enhanced pro-inflammatory cytokine production. in this study we focused on the macrophage (mphi), which besides being an important source of such cytokines, is known to be an important pla ...200415380774
identification of proteins associated with murine cytomegalovirus virions.proteins associated with the murine cytomegalovirus (mcmv) viral particle were identified by a combined approach of proteomic and genomic methods. purified mcmv virions were dissociated by complete denaturation and subjected to either separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and in-gel digestion or treated directly by in-solution tryptic digestion. peptides were separated by nanoflow liquid chromatography and analyzed by tandem mass spectrometry (lc-ms/ms). the ms/ ...200415452238
multiple epitopes in the murine cytomegalovirus early gene product m84 are efficiently presented in infected primary macrophages and contribute to strong cd8+-t-lymphocyte responses and protection following dna immunization.we previously demonstrated that after vaccination of balb/c mice with dna encoding murine cytomegalovirus (mcmv) ie1 or m84, a similar level of protection against mcmv infection was achieved. however, the percentage of antigen-specific cd8(+) t cells elicited by ie1 was higher than that by m84 as measured by intracellular cytokine staining when splenocytes were stimulated with an epitope peptide (m. ye at al., j. virol. 76:2100-2112, 2002). we show here that after dna vaccination with m84, a hig ...200415452242
the cytomegalovirus m155 gene product subverts natural killer cell antiviral protection by disruption of h60-nkg2d interactions.natural killer (nk) cells are an important early mediator of host immunity to murine cytomegalovirus (mcmv) infection. however, mcmv has evolved mechanisms to elude recognition and clearance by nk cells. we have identified an mcmv immune evasion protein that impairs nkg2d-mediated nk cell antiviral activity. infection of balb/c 3t3 cells with the smith strain of mcmv resulted in strong down-regulation of h60, a high affinity ligand for nkg2d, from the surface of virus-infected cells. the mcmv m1 ...200415477345
perforin knockout mice, but not mice with maids, show protection against experimental cytomegalovirus retinitis after adoptive transfer of immune cells with a functional perforin cytotoxic pathway.adoptive transfer studies were performed to test the hypothesis that the perforin cytotoxic pathway is more important than the fas/fasl cytotoxic pathway in protection against experimental murine cytomegalovirus (mcmv) retinitis. splenic immune cells from donor mcmv-immunized normal mice or gld mice deficient in fas/fasl-mediated cytotoxicity significantly reduced the frequency and severity of mcmv retinitis following subretinal mcmv challenge when transferred into recipient pko mice deficient i ...200415503209
the murine cytomegalovirus m73.5 gene, a member of a 3' co-terminal alternatively spliced gene family, encodes the gp24 virion glycoprotein.we have identified a novel family of five 3' co-terminal transcripts in murine cytomegalovirus (mcmv) arranged in a tail-to-tail orientation with respect to the mcmv glycoprotein h (gh) gene m75. they share the same exon 2 sequence but possess different exon 1 sequences. two of these spliced transcripts (m73) encode the mcmv homolog of glycoprotein n (gn) entirely within exon 1. two other transcripts designated m73.5 encode a previously described virion glycoprotein gp24 that shares its first 20 ...200415518804
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