| 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 ... | 2005 | 15709020 |
| cytomegalovirus induces t-cell independent apoptosis in brain during immunodeficiency. | cytomegalovirus (cmv) is the most common opportunistic viral pathogen associated with hiv/aids or immunosuppressive therapy. systemic pathology may be caused either through direct virus-mediated infection or by indirect mechanisms such as 'by-stander' apoptosis. cmv infection of the central nervous system (cns) occurs late in disease progression and understanding of pathology in the brain is fundamental for selection of appropriate therapies. | 2005 | 15722026 |
| in vitro activity and mechanism of action of methylenecyclopropane analogs of nucleosides against herpesvirus replication. | we have reported previously that methylenecyclopropane analogs of nucleosides have excellent activity against certain members of the herpesvirus family. a second generation, the 2,2-bis-hydroxymethyl derivatives, were synthesized, and 18 compounds were tested for activity in vitro against herpes simplex virus types 1 and 2 (hsv-1 and hsv-2), human and murine cytomegalovirus (hcmv and mcmv), varicella-zoster virus (vzv), and epstein-barr virus (ebv). selected analogs were also evaluated against h ... | 2005 | 15728900 |
| complex formation among murine cytomegalovirus us22 proteins encoded by genes m139, m140, and m141. | the murine cytomegalovirus (mcmv) proteins encoded by us22 genes m139, m140, and m141 function, at least in part, to regulate replication of this virus in macrophages. mutant mcmv having one or more of these genes deleted replicates poorly in macrophages in culture and in the macrophage-dense environment of the spleen. in this report, we demonstrate the existence of stable complexes formed by the products of all three of these us22 genes, as well as a complex composed of the products of m140 and ... | 2005 | 15731247 |
| nk gene complex haplotype variability and host resistance alleles to murine cytomegalovirus in wild mouse populations. | the nk gene complex (nkc) on mouse chromosome 6 encodes receptors that are expressed on nk cells, such as ly49h, and is involved in regulating nk cell control of virus infections, such as murine cytomegalovirus (mcmv). in the present study, we investigated the level of allelic heterogeneity in nkc loci in populations of outbred wild mice. this work revealed extensive levels of heterogeneity within two wild mouse populations. analysis of mcmv replication in a population of specific pathogen-free ... | 2005 | 15748210 |
| characterization and regulation of essential murine cytomegalovirus genes m142 and m143. | us22 gene family members m142 and m143 are essential for replication of murine cytomegalovirus (mcmv). their transcripts are produced with immediate-early kinetics, but little else is known about these viral genes. unlike their transcripts, the m142 and m143 gene products (pm142, pm143) were not expressed until early times post-infection, with levels increasing over the course of infection. both pm142 and pm143 were predominantly cytoplasmic, but cellular fractionation studies confirmed that the ... | 2005 | 15780867 |
| species-specificity of a murine immunocontraceptive utilising murine cytomegalovirus as a gene delivery vector. | cytomegaloviruses are species-specific dna viruses. recombinant murine cytomegaloviruse (mcmv) expressing the mouse egg-coat protein zona pellucida 3 (mzp3) has been shown to sterilise female mice by breaking self-tolerance and inducing an immune response against the host zp3. this virus has the potential to be used for mouse population control, however the effect of this recombinant immunocontraceptive virus in non-host species must be determined. recombinant mcmv-mzp3, based on both laboratory ... | 2005 | 15811641 |
| real-time pcr quantitation of hepatitis b virus dna using automated sample preparation and murine cytomegalovirus internal control. | quantitation of circulating hepatitis b virus (hbv) dna is important for monitoring disease progression and for assessing the response to antiviral therapy. several commercial and 'in house' assays for hbv dna quantitation have been described but many of these have limitations of relatively low sensitivity and limited dynamic range. this study describes the development and evaluation of a fret-based real-time pcr assay designed to overcome these limitations and to provide accurate quantitation o ... | 2005 | 15847939 |
| self hsp60 peptide serves as an immunogenic carrier for a ctl epitope against persistence of murine cytomegalovirus in the salivary gland. | murine cytomegalovirus (mcmv) infection is associated with persistence of virus in the salivary glands, despite relatively rapid clearance of virus from the spleen. an effective immunization against mcmv should prevent such viral persistence. we previously reported that a peptide (p458) from the sequence of the 60 kda heat shock protein (hsp60) molecule in a conjugate vaccine can provide t cell help for the induction of protecting antibody against bacterial capsular polysaccharides. we now repor ... | 2005 | 15855009 |
| elimination of ie1 significantly attenuates murine cytomegalovirus virulence but does not alter replicative capacity in cell culture. | the major immediate-early (mie) genes of cytomegaloviruses (cmv) are broadly thought to be decisive regulators of lytic replication and reactivation from latency. to directly assess the role of the mie protein ie1 during the infection of murine cmv (mcmv), we constructed an mcmv with exon 4 of the ie1 gene deleted. we found that, independent of the multiplicity of infection, the resulting recombinant virus, mcmvdie1, which fails to express the ie1 protein, was fully competent for early gene expr ... | 2005 | 15890957 |
| epistasis between mouse klra and major histocompatibility complex class i loci is associated with a new mechanism of natural killer cell-mediated innate resistance to cytomegalovirus infection. | experimental infection with mouse cytomegalovirus (mcmv) has been used to elucidate the intricate host-pathogen mechanisms that determine innate resistance to infection. linkage analyses in f(2) progeny from mcmv-resistant ma/my (h2 (k)) and mcmv-susceptible balb/c (h2 (d)) and balb.k (h2 (k)) mouse strains indicated that only the combination of alleles encoded by a gene in the klra (also called ly49) cluster on chromosome 6, and one in the major histocompatibility complex (h2) on chromosome 17, ... | 2005 | 15895081 |
| infection of retinal neurons during murine cytomegalovirus retinitis. | previous results suggest that retinal neurons are infected early during murine cytomegalovirus (mcmv) infection of the inner retina. the purposes of this study were to identify which retinal neurons are infected and to determine the routes by which mcmv spreads in the retina. | 2005 | 15914622 |
| mouse cytomegalovirus antigenic immune stimulation is sufficient to aggravate atherosclerosis in hypercholesterolemic mice. | we have previously demonstrated that mouse cytomegalovirus (mcmv) infection aggravates atherosclerosis by stimulating the ongoing inflammatory process in the vascular wall. here we investigated whether mcmv antigenic immune stimulation by uv-mcmv injection is sufficient to aggravate atherosclerosis. in addition we analyzed whether low viral doses are sufficient to stimulate atherosclerosis. therefore, apoe(-/-) mice received a low dose injection with infectious virus (mcmv) or replication-defici ... | 2005 | 15939052 |
| a murine model of dual infection with cytomegalovirus and pneumocystis carinii: effects of virus-induced immunomodulation on disease progression. | despite the use of antimicrobial prophylaxis, cytomegalovirus (cmv) and pneumocystis carinii (pc) pneumonia (pcp) are both leading causes of morbidity and mortality in immunocompromised patients. it has previously been reported that cmv infection modulates host immune responses with a variety of mechanisms which include the suppression of helper t cell functions and antigen presenting cell (apc) functions, both of which are critical for pcp resolution. however, the mechanisms of these interactio ... | 2005 | 16002171 |
| frequent coinfection of cells explains functional in vivo complementation between cytomegalovirus variants in the multiply infected host. | in contrast to many other virus infections, primary cytomegalovirus (cmv) infection does not fully protect against reinfection. accordingly, clinical data have revealed a coexistence of multiple human cmv variants/strains in individual patients. notably, the phenomenon of multiple infection was found to correlate with increased virus load and severity of cmv disease. although of obvious medical relevance, the mechanism underlying this correlation is unknown. a weak immune response in an individu ... | 2005 | 16014912 |
| cd4+ t-cell reconstitution reduces cytomegalovirus in the immunocompromised brain. | cytomegalovirus (cmv) infection is the most common opportunistic infection of the central nervous system in patients with human immunodeficiency virus or aids or on immunosuppressive drug therapy. despite medical management, infection may be refractory to treatment and continues to cause significant morbidity and mortality. we investigated adoptive transfer as an approach to treat and prevent neurotropic cmv infection in an adult immunodeficient mouse model. scid mice were challenged with intrac ... | 2005 | 16014915 |
| inhibition of protein kinases c prevents murine cytomegalovirus replication. | for successful establishment of infection and initiation of the replication cycle, murine cytomegalovirus (mcmv) utilizes cellular structures and functions, including cell-membrane penetration, capsid dismantling and cytosolic transport of viral dna into the nucleus. these early events of mcmv infections are dependent on cellular regulatory mechanisms, primarily protein phosphorylation. in the present study, protein kinase inhibitors were used to explore the role of protein phosphorylation media ... | 2005 | 16033962 |
| transmission of two australian strains of murine cytomegalovirus (mcmv) in enclosure populations of house mice (mus domesticus). | to control plagues of free-living mice (mus domesticus) in australia, a recombinant murine cytomegalovirus (mcmv) expressing fertility proteins is being developed as an immunocontraceptive agent. real-time quantitative pcr was used to monitor the transmission of two genetically variable field strains of mcmv through mouse populations after 25% of founding mice were infected with the n1 strain, followed by the g4 strain 6 weeks later. pathogen-free wild-derived mice were released into outdoor enc ... | 2005 | 16050517 |
| mouse cytomegalovirus m33 is necessary and sufficient in virus-induced vascular smooth muscle cell migration. | mouse cytomegalovirus (mcmv) encodes two potential seven-transmembrane-spanning proteins with homologies to cellular chemokine receptors, m33 and m78. while these virus-encoded chemokine receptors are necessary for the in vivo pathogenesis of mcmv, the function of these proteins is unknown. since vascular smooth muscle cell (smc) migration is of critical importance for the development of atherosclerosis and other vascular diseases, the ability of m33 to promote smc motility was assessed. similar ... | 2005 | 16051870 |
| use of quantitative real-time pcr (qrt-pcr) to measure cytokine transcription and viral load in murine cytomegalovirus infection. | a quantitative real-time pcr (qrt-pcr) assay was developed to measure cytokine transcription profiles and viral load during sub-clinical and clinical infection with murine cytomegalovirus (mcmv). primers/fluorogenic probes specific for mouse cytokines and for the immediate early gene 1 (ie1) of mcmv were used to quantitate cytokine responses and viral load in various organs of mcmv infected mice. increased mrna levels of tnf-alpha, inf-gamma and il-10 were detected in the spleens, lungs and live ... | 2006 | 16140399 |
| novel functions of tyrosine kinase 2 in the antiviral defense against murine cytomegalovirus. | we have recently reported that tyrosine kinase 2 (tyk2)-deficient mice have a selective defect in the in vivo defense against certain viruses. in our current study we show that tyk2 is essential for the defense against murine cmv (mcmv). in vivo challenges with mcmv revealed impaired clearance of virus from organs and decreased survival of mice in the absence of tyk2. our in vitro studies demonstrate that mcmv replicates to dramatically higher titers in tyk2-deficient macrophages compared with w ... | 2005 | 16148148 |
| murine cytomegalovirus (mcmv) spreads to and replicates in the retina after endotoxin-induced disruption of the blood-retinal barrier of immunosuppressed balb/c mice. | the goal of this study was to determine whether disruption of the blood-retinal barrier (brb) facilitates spread of mcmv to the retina in immunosuppressed (is) balb/c mice. is mice were inoculated intravenously (i.v.) with murine cytomegalovirus (mcmv) or with macrophages infected with mcmv for 4 days in vitro. the brb was disrupted by injection of sodium iodate (i.v.) or lipopolysaccharide (lps, i.v. or anterior chamber). frozen sections of ocular tissue were examined for mcmv antigens. the res ... | 2005 | 16162479 |
| the effects of allitridin on the expression of transcription factors t-bet and gata-3 in mice infected by murine cytomegalovirus. | this study was designed to investigate the effects of allitridin on the expression of transcription factors t-bet and gata-3 in mice infected by murine cytomegalovirus (mcmv). a balb/c mouse model system of mcmv infection was established. twenty mice were allocated randomly into an allitridin-treated group (n = 10) and a placebo control group (n = 10). the same dose (25 mg/kg/day) and regimen of allitridin were used in the treated group in the 24 hours after virus infection; the same volume of s ... | 2005 | 16176143 |
| requisite h2k role in nk cell-mediated resistance in acute murine cytomegalovirus-infected ma/my mice. | human cmv infections are a major health risk in patients with dysfunctional or compromised immunity, especially in patients with nk cell deficiencies, as these are frequently associated with high morbidity and mortality. in experimental murine cmv (mcmv) infections, ly49h activation receptors on c57bl/6 (b6) nk cells engage m157 viral ligands on mcmv-infected cells and initiate dominant virus control. in this study, we report that mcmv resistance in ma/my relies on ly49h-independent nk cell-medi ... | 2005 | 16272339 |
| assessing the genetic component of the susceptibility of mice to viral infections. | laboratory mice often exhibit wide differences in susceptibility when infected experimentally with viruses. based on such observations, experiments have been designed to investigate the determinism of these differences at the molecular level, and a few genes that play a major role in the innate mechanisms of defence of the species toward viral aggressions have been characterised. for example, the extraordinary resistance of sjl mice to experimental infections with hepatitis virus strain a59 is t ... | 2005 | 16420748 |
| multiple sclerosis and virus induced immune responses: autoimmunity can be primed by molecular mimicry and augmented by bystander activation. | polymicrobial infections have been associated with plausible immune mediated diseases, including multiple sclerosis (ms). virus infection can prime autoimmune t cells specific for central nervous system (cns) antigens, if virus has molecular mimicry with cns proteins. on the other hand, infection of irrelevant viruses will induce two types of cytokine responses. infection with a virus such as lymphocytic choriomeningitis virus (lcmv), can induce interferon (ifn)-alpha/beta production and suppres ... | 2006 | 16455578 |
| genome-wide analysis reveals a highly diverse cd8 t cell response to murine cytomegalovirus. | human cmv establishes a lifelong latent infection in the majority of people worldwide. although most infections are asymptomatic, immunocompetent hosts devote an extraordinary amount of immune resources to virus control. to increase our understanding of cmv immunobiology in an animal model, we used a genomic approach to comprehensively map the c57bl/6 cd8 t cell response to murine cmv (mcmv). responses to 27 viral proteins were detectable directly ex vivo, the most diverse cd8 t cell response ye ... | 2006 | 16517745 |
| specific remodeling of splenic architecture by cytomegalovirus. | efficient immune defenses are facilitated by the organized microarchitecture of lymphoid organs, and this organization is regulated by the compartmentalized expression of lymphoid tissue chemokines. mouse cytomegalovirus (mcmv) infection induces significant remodeling of splenic microarchitecture, including loss of marginal zone macrophage populations and dissolution of t and b cell compartmentalization. mcmv preferentially infected the splenic stroma, targeting endothelial cells (ec) as reveale ... | 2006 | 16518465 |
| pulmonary cytomegalovirus reactivation causes pathology in immunocompetent mice. | cytomegalovirus (cmv) is a ubiquitous herpes virus that persists in the host in a latent state following primary infection. we have recently observed that cmv reactivates in lungs of critically ill surgical patients and that this reactivation can be triggered by bacterial sepsis. although cmv is a known pathogen in immunosuppressed transplant patients, it is unknown whether reactivated cmv is a pathogen in immunocompetent hosts. using an animal model of latency/reactivation, we studied the patho ... | 2006 | 16521279 |
| virulence and attenuation of murine cytomegalovirus. | murine cytomegalovirus (mcmv) was rapidly and regularly attenuated by passage through mouse embryo cell culture. this attenuation was manifested by alteration of lethality for suckling mice and by a striking loss of capacity to multiply in liver and spleen of weanling mice. the attenuation was selective in that the passaged virus multiplied vigorously in other organs and established high titer infections in submaxillary glands and pancreas comparable to those seen with wild virus. furthermore, a ... | 1971 | 16557958 |
| cytokine and chemokine networks: pathways to antiviral defense. | the complex interplays between cytokines and chemokines are emerging as key communication signals in the shaping of innate and adaptive immune responses against foreign pathogens, including viruses. in particular, the virus-induced expression of cytokine and chemokine profiles drives the recruitment and activation of immune effector cells to sites of tissue infection. under the conditions of infection with murine cytomegalovirus (mcmv), a herpesvirus with pathogenic potential, early immune funct ... | 2006 | 16570855 |
| murine cytomegalovirus interference with antigen presentation contributes to the inability of cd8 t cells to control virus in the salivary gland. | compared to other organs, murine cytomegalovirus (mcmv) replication in the salivary gland is uniquely resistant to cd8 t-cell control. the contribution of viral genes that interfere with antigen presentation (viprs) to this resistance was assessed using a mutant lacking mcmv's known viprs. salivary gland titers of the vipr-deficient virus were at least 10-fold lower than those of the wild type during the persistent phase of infection; the defect was reversed by depleting cd8 t cells. thus, viprs ... | 2006 | 16571839 |
| lymphoma cell apoptosis in the liver induced by distant murine cytomegalovirus infection. | cytomegalovirus (cmv) poses a threat to the therapy of hematopoietic malignancies by hematopoietic stem cell transplantation, but efficient reconstitution of antiviral immunity prevents cmv organ disease. tumor relapse originating from a minimal residual leukemia poses another threat. although a combination of risk factors was supposed to enhance the incidence and severity of transplantation-associated disease, a murine model of a liver-adapted b-cell lymphoma has previously shown a survival ben ... | 2006 | 16641273 |
| murine cytomegalovirus infection markedly reduces serum mcp-1 levels in mcp-1 transgenic mice. | monocyte chemoattractant protein-1 (mcp-1) is a pro-inflammatory chemokine believed to play a major role in atherogenesis. injured endothelial cells express mcp-1, which attracts monocytes to the blood vessel wall and leads to the formation of atheromas. cytomegalovirus infection may also play a role in atherogenesis and accelerates inflammation in tissues that overexpress mcp-1. to examine the relationship of cytomegalovirus infection and mcp-1, we infected mcp-1 transgenic mice with murine cyt ... | 2006 | 16682515 |
| analysis of the mcmv resistome by enu mutagenesis. | the mouse cytomegalovirus (mcmv) resistome is the set of host genes with nonredundant functions in resistance to mcmv infection. by screening 3,500 g(3) germline mutant mice ( approximately 1,750 gamete equivalents), we have identified eight transmissible mutations that create mcmv susceptibility in c57bl/6 mice. among these, a mutation called domino was noted to cause macrophage susceptibility to vesicular stomatitis virus (vsv) in vitro. this accessory phenotype was not corrected by type i int ... | 2006 | 16688530 |
| transfusion-transmitted cytomegalovirus (cmv) infections in a murine model: characterization of cmv-infected donor mice. | donor and recipient mechanisms that modulate the incidence and severity of transfusion-transmitted cytomegalovirus (tt-cmv) are unclear. the kinetics of murine cmv (mcmv) infection in the peripheral blood of donor mice were investigated to determine the utility of this model for studying tt-cmv. | 2006 | 16734804 |
| the herpesviral fc receptor fcr-1 down-regulates the nkg2d ligands mult-1 and h60. | members of the alpha- and beta-subfamily of herpesviridae encode glycoproteins that specifically bind to the fc part of immunoglobulin (ig)g. plasma membrane resident herpesviral fc receptors seem to prevent virus-specific igg from activating antibody-dependent effector functions. we show that the mouse cytomegalovirus (mcmv) molecule fcr-1 promotes a rapid down-regulation of nkg2d ligands murine ul16-binding protein like transcript (mult)-1 and h60 from the cell surface. deletion of the m138/fc ... | 2006 | 16831899 |
| mouse cytomegalovirus crosses the species barrier with help from a few human cytomegalovirus proteins. | strong species specificity and similar tropisms suggest mouse cytomegalovirus (mcmv) as a potential vector for transgenes into human cells. we reexamined the dogma that mouse cytomegalovirus cannot productively replicate in human cells and found that mouse cytomegalovirus can produce infectious particles albeit at a level that does not sustain an infection. this finding demonstrates that mouse cytomegalovirus can undergo all processes of its life cycle in human cells but may not be well adapted ... | 2006 | 16840331 |
| pentraxin 3 protects from mcmv infection and reactivation through tlr sensing pathways leading to irf3 activation. | reactivation of latent human cytomegalovirus (hcmv) following allogeneic transplantation is a major cause of morbidity and mortality and predisposes to severe complications, including superinfection by aspergillus species (spp). antimicrobial polypeptides, including defensins and mannan-binding lectin, are known to block viral fusion by cross-linking sugars on cell surface. pentraxin 3 (ptx3), a member of the long pentraxin family, successfully restored antifungal immunity in experimental hemato ... | 2006 | 16840729 |
| induction of early murine cytomegalovirus infection by different reporter gene-associated recombinant viruses. | murine cytomegalovirus (mcmv) has provided useful models for acute, chronic and latent cmv infection because of its similarities in structure and biology with human cmv. we report the induction of acute mcmv hepatitis with different bacterial artificial chromosome (bac)-cloned virus constructs [mcmv-seap which includes the gene for secreted alkaline phosphatase (seap) under rous sarcoma virus (rsv)-promoter control, mcmv-gfp which includes the gene for enhanced green fluorescent protein (egfp) u ... | 2006 | 16842438 |
| effect of [ca2+]i and neuronal mitochondria transmembrane potentials in hippocampus of murine cytomegalovirus infected mice. | to explore the effect of [ca2+]i and neuronal mitochondria transmembrane potentials in hippocampus of murine cytomegalovirus (mcmv) infected mice, newborn balb/c mice were randomly divided into two groups: a virus inoculated group and a control group. after 56 days, single cell of hippocampus was isolated, and mitochondria transmembrane potentials and the intracellular free calcium level [ca2+]i in hippocampus were measured by means of flow cytometry (fcm). compared with the control group, the m ... | 2006 | 16850749 |
| coordinated function of murine cytomegalovirus genes completely inhibits ctl lysis. | murine cmv (mcmv) encodes three viral genes that interfere with ag presentation (viprs) to cd8 t cells, m04, m06, and m152. because the functional impact of these genes during normal infection of c57bl/6 mice is surprisingly modest, we wanted to determine whether the viprs are equally effective against the entire spectrum of h-2(b)-restricted cd8 t cell epitopes. we also wanted to understand how the viprs interact at a functional level. to address these questions, we used a panel of mcmv mutants ... | 2006 | 16920962 |
| cd8 t cells control cytomegalovirus latency by epitope-specific sensing of transcriptional reactivation. | during murine cytomegalovirus (mcmv) latency in the lungs, most of the viral genomes are transcriptionally silent at the major immediate-early locus, but rare and stochastic episodes of desilencing lead to the expression of ie1 transcripts. this low-frequency but perpetual expression is accompanied by an activation of lung-resident effector-memory cd8 t cells specific for the antigenic peptide 168-yphfmptnl-176, which is derived from the ie1 protein. these molecular and immunological findings we ... | 2006 | 16928768 |
| adenoviral vector platform for transduction of constitutive and regulated tricistronic or triple-transcript transgene expression in mammalian cells and microtissues. | adenoviral particles can efficiently transduce a broad spectrum of cell types, so they are widely used in basic research and clinical trials. | 2006 | 16960915 |
| 9-{[3-fluoro-2-(hydroxymethyl)cyclopropylidene]methyl}adenines and -guanines. synthesis and antiviral activity of all stereoisomers1. | all stereoisomers of adenine and guanine methylene-3-fluoromethylenecyclopropane analogues of nucleosides 9a, 9b, 10a, 10b, 11a, 11b, 12a, and 12b were synthesized and their antiviral activities were evaluated. a highly convergent approach permitted the synthesis of all these analogues using a single intermediate 15. reaction of aldehyde 13 with fluorotrichloromethane and tri-n-butylphosphine gave fluoroalkenes 14a+14b (83:17). addition of carbene derived from ethyl diazoacetate gave cyclopropan ... | 2006 | 17004726 |
| common and specific properties of herpesvirus ul34/ul31 protein family members revealed by protein complementation assay. | the proteins encoded by the ul34 and ul31 genes of herpes simplex virus are conserved among herpesviruses. they form a complex that is essential for the egress of the herpesvirus nucleocapsids from the nucleus. in previous work on the homologous protein complex in murine cytomegalovirus (mcmv), we defined their mutual binding domains. here, we started to map binding domains within the ul34/ul31 proteins of alpha-, beta-, and gammaherpesviruses and to locate other functional properties. a protein ... | 2006 | 17005637 |
| double-stranded rna binding by a heterodimeric complex of murine cytomegalovirus m142 and m143 proteins. | in response to viral infection, cells activate a variety of antiviral responses, including several that are triggered by double-stranded (ds) rna. among these are the protein kinase r and oligoadenylate synthetase/rnase l pathways, both of which result in the shutoff of protein synthesis. many viruses, including human cytomegalovirus, encode dsrna-binding proteins that prevent the activation of these pathways and thereby enable continued protein synthesis and viral replication. we have extended ... | 2006 | 17005694 |
| murine cytomegalovirus m142 and m143 are both required to block protein kinase r-mediated shutdown of protein synthesis. | cytomegaloviruses carry the us22 family of genes, which have common sequence motifs but diverse functions. only two of the 12 us22 family genes of murine cytomegalovirus (mcmv) are essential for virus replication, but their functions have remained unknown. in the present study, we deleted the essential us22 family genes, m142 and m143, from the mcmv genome and propagated the mutant viruses on complementing cells. the m142 and the m143 deletion mutants were both unable to replicate in noncompleme ... | 2006 | 17005695 |
| deficient major histocompatibility complex-linked innate murine cytomegalovirus immunity in ma/my.l-h2b mice and viral downregulation of h-2k class i proteins. | nk cells are key effectors of innate immunity and host survival during cytomegalovirus (cmv) infection. innate murine cmv (mcmv) resistance in ma/my mice requires ly49h/m157-independent h-2k-linked nk cell control. here we show that replacement of ma/my h-2k with c57l h-2b susceptibility genes led to a remarkable loss of innate virus immunity, though nk gamma interferon was induced in h-2b and h-2k strains shortly after infection. thus, h-2b genes expressed in c57l or ma/my.l-h2b are sufficient ... | 2007 | 17050600 |
| cytomegalovirus induces interferon-stimulated gene expression and is attenuated by interferon in the developing brain. | cytomegalovirus (cmv) is considered the most common infectious agent causing permanent neurological dysfunction in the developing brain. we have previously shown that cmv infects developing brain cells more easily than it infects mature brain cells and that this preference is independent of the host b- and t-cell responses. in the present study, we examined the innate antiviral defenses against mouse (m) and human (h) cmvs in developing and mature brain and brain cells. mcmv infection induced in ... | 2007 | 17065212 |
| viral vectored immunocontraception: screening of multiple fertility antigens using murine cytomegalovirus as a vaccine vector. | mouse cytomegalovirus (mcmv) has previously been used as a vaccine vector for viral vectored immunocontraception (vvic). mcmv expressing murine zona pellucida 3 (mzp3) induces long term infertility in up to 100% of female balb/c mice following a single inoculation. whilst a large number of antigens have been investigated as potential immunocontraceptive vaccines, it has been difficult to compare these antigens as few studies have used identical approaches or even animal species. here a range of ... | 2007 | 17070624 |
| severe focal sialadenitis and dacryoadenitis in nzm2328 mice induced by mcmv: a novel model for human sjögren's syndrome. | the genetic and environmental factors that control the development of sjögren's syndrome, an autoimmune disease mainly involving the salivary and lacrimal glands, are poorly understood. viruses which infect the glands may act as a trigger for disease. the ability of sialotropic murine cmv (mcmv) to induce acute and chronic glandular disease was characterized in an autoimmune-prone mouse strain, nzm2328. mcmv levels were detectable in the salivary and lacrimal glands 14-28 days after i.p. infecti ... | 2006 | 17082658 |
| cxcr3-dependent recruitment of antigen-specific t lymphocytes to the liver during murine cytomegalovirus infection. | innate inflammatory events promoting antiviral defense in the liver against murine cytomegalovirus (mcmv) infection have been characterized. however, the mechanisms that regulate the selective recruitment of inflammatory t lymphocytes to the liver during mcmv infection have not been defined. the studies presented here demonstrate the expression of monokine induced by gamma interferon (ifn-gamma; mig/cxcl9) and ifn-gamma-inducible protein 10 (ip-10/cxcl10) in liver leukocytes and correlate their ... | 2007 | 17108043 |
| viral interference with b7-1 costimulation: a new role for murine cytomegalovirus fc receptor-1. | murine cmv (mcmv), a beta-herpesvirus, infects dendritic cells (dc) and impairs their function. the underlying events are poorly described. in this study, we identify mcmv m138 as the viral gene responsible for promoting the rapid disappearance of the costimulatory molecule b7-1 (cd80) from the cell surface of dc. this was unexpected, as m138 was previously identified as fcr-1, a putative virus-encoded fcr. m138 impaired the ability of dc to activate cd8+ t cells. biochemical analysis and immuno ... | 2006 | 17142739 |
| characterization of the murine cytomegalovirus m136 gene. | the 230-kbp murine cytomegalovirus (mcmv) genome is predicted to encode 182 open reading frames (orfs). one gene whose functional role is not known is encoded by the 762-bp m136 orf. sequence analysis of rat cytomegalovirus (rcmv) strains maastricht and english revealed homologous orfs, pr136, and orf hj4, respectively. conservation of these orfs suggested that m136 and the rcmv homologs might play a role during virus replication. expression of an epitope tagged form of m136 (m136-v5) yielded a ... | 2007 | 17143724 |
| the interplay between host and viral factors in shaping the outcome of cytomegalovirus infection. | cytomegalovirus (cmv) remains a major human pathogen causing significant morbidity and mortality in immunosuppressed or immunoimmature individuals. although significant advances have been made in dissecting out certain features of the host response to human cmv (hcmv) infection, the strict species specificity of cmvs means that most aspects of antiviral immunity are best assessed in animal models. the mouse model of murine cmv (mcmv) infection is an important tool for analysis of in vivo feature ... | 2007 | 17146464 |
| lack of inos facilitates mcmv spread in the retina. | the purposes of this study were to identify inos-producing retinal cells and to determine whether lack of inos facilitates mcmv spread and replication in the retina. | 2007 | 17197545 |
| mutations in the temperature-sensitive murine cytomegalovirus (mcmv) mutants tsm5 and tsm30: a study of genes involved in immune evasion, dna packaging and processing, and dna replication. | a murine cytomegalovirus (mcmv) temperature-sensitive (ts) mutant, tsm5, of the k181 (birmingham) strain, showed approximately 10-fold and approximately 10,000-fold reductions in yields at the permissive (33 degrees c) and non-permissive temperature (40 degrees c), respectively. it did not replicate to detectable levels in any tissue of 1-week-old balb/c mice for up to 21 days following i.p. inoculation with 4 x 10(3) pfu although it did replicate, albeit with considerably delayed kinetics, in s ... | 2007 | 17245727 |
| dynamics of killer t cell inflation in viral infections. | upon acute viral infection, a typical cytotoxic t lymphocyte (ctl) response is characterized by a phase of expansion and contraction after which it settles at a relatively stable memory level. recently, experimental data from mice infected with murine cytomegalovirus (mcmv) showed different and unusual dynamics. after acute infection had resolved, some antigen specific ctl started to expand over time despite the fact that no replicative virus was detectable. this phenomenon has been termed as "c ... | 2007 | 17251133 |
| induction of natural killer cell responses by ectromelia virus controls infection. | natural killer (nk) cells play a pivotal role in the innate immune response to viral infections, particularly murine cytomegalovirus (mcmv) and human herpesviruses. in poxvirus infections, the role of nk cells is less clear. we examined disease progression in c57bl/6 mice after the removal of nk cells by both antibody depletion and genetic means. we found that nk cells were crucial for survival and the early control of virus replication in spleen and to a lesser extent in liver in c57bl/6 mice. ... | 2007 | 17287257 |
| a focused salivary gland infection with attenuated mcmv: an animal model with prevention of pathology associated with systemic mcmv infection. | while the salivary gland has been recognized as an important effector site of the common mucosal immune system, a useful model for studying anti-viral salivary gland immune responses in vivo and for exploring the role of the salivary gland within the common mucosal system has been lacking. murine cytomegalovirus (mcmv) is a beta-herpesvirus that displays a strong tropism for the salivary gland and produces significant morbidity in susceptible mice when introduced by intraperitoneal (i.p.) inocul ... | 2007 | 17320076 |
| extensive sequence variation exists among isolates of murine cytomegalovirus within members of the m02 family of genes. | murine cytomegalovirus (mcmv) is a widely used model for human cytomegalovirus (hcmv) and has facilitated many important discoveries about the biology of cmvs. most of these studies are conducted using the laboratory mcmv strains smith and k181. however, wild-derived isolates of mcmv, like hcmv clinical isolates, exhibit genetic variation from laboratory strains, particularly at the ends of their genomes in areas containing known or putative immune-evasion and tropism genes. this study analysed ... | 2007 | 17325348 |
| role of the indigenous microbiota in maintaining the virus-specific cd8 memory t cells in the lung of mice infected with murine cytomegalovirus. | the potent role of indigenous microbiota in maintaining murine cmv (mcmv)-specific memory t cells, which were measured by multimer staining, was investigated using germfree (gf) mice. when the balb/c mice bred under specific pathogen-free (spf) conditions were i.p. infected with 0.2 ld(50) of mcmv, high frequencies of cd69(+)/cd44(+) mcmv-specific cd8 t cells were noted in the lungs even at 6-12 mo after infection (11.1 +/- 3.2 and 9.8 +/- 0.9%, respectively). in contrast, even though the viral ... | 2007 | 17404304 |
| upregulation of cd94/nkg2a receptors and qa-1b ligand during murine cytomegalovirus infection of salivary glands. | following acute infection, murine cytomegalovirus (mcmv) replicates persistently in the salivary glands, despite the vigorous response of activated cd8 t cells that infiltrate this gland. virus-specific cd8 t lymphocytes isolated from this organ were found to express the inhibitory cd94/nkg2a receptor that, in some virus models, confers an inhibitory response to cytotoxic t lymphocytes (ctls). in response to mcmv infection, expression of the cd94/nkg2a ligand, qa-1b, increased dramatically in th ... | 2007 | 17412971 |
| jinx, an mcmv susceptibility phenotype caused by disruption of unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis. | mouse cytomegalovirus (mcmv) susceptibility often results from defects of natural killer (nk) cell function. here we describe jinx, an n-ethyl-n-nitrosourea-induced mcmv susceptibility mutation that permits unchecked proliferation of the virus, causing death. in jinx homozygotes, activated nk cells and cytotoxic t lymphocytes (ctls) fail to degranulate, although they retain the ability to produce cytokines, and cytokine levels are markedly elevated in the blood of infected mutant mice. jinx was ... | 2007 | 17420270 |
| human herpesvirus-6a and -6b encode viral immunoevasins that downregulate class i mhc molecules. | like all other members of the herpesvirus family, the closely related human herpesviruses-6 and -7 (hhv-6,7) persist in their host throughout life. in so doing, without exception, every member of the herpesvirus family has evolved mechanisms to avoid detection by the immune system. in particular, human cytomegalovirus (hcmv), mouse cytomegalovirus (mcmv), human herpesvirus-8 (hhv-8), and herpes simplex virus (hsv) all encode multiple proteins that interfere with proper mhc class i antigen presen ... | 2007 | 17467766 |
| dna immunization using highly conserved murine cytomegalovirus genes encoding homologs of human cytomegalovirus ul54 (dna polymerase) and ul105 (helicase) elicits strong cd8 t-cell responses and is protective against systemic challenge. | human cytomegalovirus (hcmv) establishes a lifelong infection with the potential for reinfection or viral transmission even in the presence of strong and diverse cd8 t-lymphocyte responses. this suggests that the cmvs skew the host t-cell response in order to favor viral persistence. in this study, we hypothesized that the essential, nonstructural proteins that are highly conserved among the cmvs may represent a novel class of t-cell targets for vaccine-mediated protection due to their requireme ... | 2007 | 17507492 |
| viral interference with antigen presentation does not alter acute or chronic cd8 t cell immunodominance in murine cytomegalovirus infection. | both human cmv and murine cmv (mcmv) elicit large cd8 t cell responses, despite the potent effects of viral genes that interfere with the mhc class i (mhc i) pathway of ag presentation. to investigate the impact of immune evasion on cd8 t cell priming, we infected mice with wild-type (wt) mcmv or a mutant lacking its mhc i immune evasion genes, deltam4+m6+m152 mcmv. in acute infection, the two viruses elicited a cd8 t cell response to 26 peptide epitopes that was virtually identical in total siz ... | 2007 | 17513772 |
| optimization of adenoviral vector-mediated transgene expression in the canine brain in vivo, and in canine glioma cells in vitro. | expression of the immune-stimulatory molecule fms-like tyrosine kinase 3 ligand (flt3l) and the conditional cytotoxic enzyme herpes simplex virus type 1 thymidine kinase (hsv1-tk) provides long-term immune-mediated survival of large glioblastoma multiforme (gbm) models in rodents. a limitation for predictive testing of novel antiglioma therapies has been the lack of a glioma model in a large animal. dogs bearing spontaneous gbm may constitute an attractive large-animal model for gbm, which so fa ... | 2007 | 17522335 |
| enhancement of susceptibility of adult mouse brain to cytomegalovirus infection by infusion of epidermal growth factor. | neural precursor cells, including neural stem and progenitor cells, in the subventricular zone (svz) are the main targets for cytomegalovirus (cmv) infection in developing brains. the neural precursor cells in the svz of the adult brain have been reported to respond by proliferating after infusion with epidermal growth factor (egf). here we report the susceptibility of the precursor cells in the adult mouse brain to murine cmv (mcmv) infection. adult mouse brains from 10-, 25-, and 70-week-old ( ... | 2007 | 17600840 |
| sequential polymicrobial infections lead to cns inflammatory disease: possible involvement of bystander activation in heterologous immunity. | vv(plp) is a recombinant vaccinia virus (vv) encoding myelin proteolipid protein (plp) that has been used to investigate molecular mimicry and autoimmunity. since virus infections can cause bystander activation, mice were first infected with vv(plp), and later challenged with wild-type vv, lymphocytic choriomeningitis virus (lcmv), or murine cytomegalovirus (mcmv). among the vv(plp)-primed mice, only mcmv challenge induced significant ki-67(+), cd3(+)t cell infiltration into the central nervous ... | 2007 | 17604850 |
| protection from lethal infection by adoptive transfer of cd8 t cells genetically engineered to express virus-specific innate immune receptor. | cmv infection is one of the most common complications in immunocompromised individuals, such as organ and bone marrow transplant patients. both innate and adaptive immune responses are required for defense against cmv infection. in murine cmv (mcmv) infection, strains harboring the mcmv-specific nk cell activation receptor, ly49h (klra8), are resistant. in contrast, mcmv infection of mice lacking ly49h gene causes early mortality due to uncontrolled viral replication. in this study, we report th ... | 2007 | 17617605 |
| dysregulated interferon-gamma responses during lethal cytomegalovirus brain infection of il-10-deficient mice. | murine cytomegalovirus (mcmv) brain infection induces a transient increase in chemokine production, which precedes the infiltration of cd3(+) lymphocytes. in this study, we hypothesized that an absence of anti-inflammatory cytokines would result in sustained proinflammatory neuroimmune responses. direct intracerebroventricular injection of mcmv into il-10 knockout (ko) mice produced an unexpected result: while wild-type animals controlled mcmv, the infection was lethal in il-10 ko animals. ident ... | 2007 | 17624463 |
| protection from cmv infection in immunodeficient hosts by adoptive transfer of memory b cells. | severe disease associated with cytomegalovirus (cmv) infection is still a major problem in patients who undergo transplantation. support of the patients' immune defense against the virus is a major goal in transplantation medicine. we have used the murine model of cmv (mcmv) to investigate the potential of a cell-based strategy to support the humoral antiviral immune response. immunocompetent c57bl/6 mice were infected with mcmv, and memory b cells from the immune animals were adoptively transfe ... | 2007 | 17656648 |
| chronic immune reactivity against persisting microbial antigen in the vasculature exacerbates atherosclerotic lesion formation. | the purpose of this study was to examine the relative contribution of different immunopathological mechanisms during murine cytomegalovirus (mcmv)-mediated acceleration of atheroma formation in apolipoprotein e-deficient (apoe-/-) mice. | 2007 | 17656668 |
| the feedback phase of type i interferon induction in dendritic cells requires interferon regulatory factor 8. | dendritic cells (dcs) produce type i interferons (ifns) in greater amounts than other cells, but the mechanisms remain elusive. here we studied the role of a transcription factor, irf8, in dc induction of type i ifns. upon newcastle disease virus (ndv) infection, bone marrow-derived plasmacytoid and conventional dcs induced ifn transcripts, exhibiting two-phase kinetics. the second, amplifying phase represented an ifn feedback response that accounted for much of ifn protein production. induction ... | 2007 | 17702615 |
| the effects of murine cytomegalovirus on the maturation, fertilization, cleavage and blastula formation of mouse oocytes in vitro. | to study the effects of mouse cytomegalovirus (mcmv) on the in vitro maturation, fertilization, cleavage and blastula formation of mouse oocytes, the immature oocytes were infected in vitro by mcmvs of different dosages (100 tcid(50), 10 tcid(50) and 1 tcid(50)). the oocytes were then observed for in vitro maturation, fertilization, cleavage and blastula formation and the ultrastructural changes after the culture with the viruses. our results showed that no significant differences were found in ... | 2007 | 17828514 |
| the role of nkg2d signaling in inhibition of cytotoxic t-lymphocyte lysis by the murine cytomegalovirus immunoevasin m152/gp40. | three proteins encoded by murine cytomegalovirus (mcmv) -- gp34, encoded by m04 (m04/gp34), gp48, encoded by m06 (m06/gp48), and gp40, encoded by m152 (m152/gp40) -- act together to powerfully impact the ability of primed cytotoxic cd8 t lymphocytes (ctl) to kill virus-infected cells. of these three, the impact of m152/gp40 on ctl lysis appears greater than would be expected based on its impact on cell surface major histocompatibility complex (mhc) class i. in addition to mhc class i, m152/gp40 ... | 2007 | 17855532 |
| cellular expression and crystal structure of the murine cytomegalovirus major histocompatibility complex class i-like glycoprotein, m153. | mouse cytomegalovirus (mcmv), a beta-herpesvirus that establishes latent and persistent infections in mice, is a valuable model for studying complex virus-host interactions. mcmv encodes the m145 family of putative immunoevasins with predicted major histocompatibility complex, class i (mhc-i) structure. functions attributed to some family members include down-regulation of host mhc-i (m152) and nkg2d ligands (m145, m152, and m155) and interaction with inhibitory or activating nk receptors (m157) ... | 2007 | 17897947 |
| targeted deletion of regions rich in immune-evasive genes from the cytomegalovirus genome as a novel vaccine strategy. | human cytomegalovirus (cmv), a ubiquitous human pathogen, is a leading cause of congenital infections and represents a serious health risk for the immunosuppressed patient. a vaccine against cmv is currently not available. cmv is characterized by its large genome and by multiple genes modulating the immunity of the host, which cluster predominantly at genome termini. here, we tested whether the deletion of gene blocks rich in immunomodulatory genes could be used as a novel concept in the generat ... | 2007 | 17913824 |
| discrete clusters of virus-encoded micrornas are associated with complementary strands of the genome and the 7.2-kilobase stable intron in murine cytomegalovirus. | the prevalence and importance of micrornas (mirnas) in viral infection are increasingly relevant. eleven mirnas were previously identified in human cytomegalovirus (hcmv); however, mirna content in murine cmv (mcmv), which serves as an important in vivo model for cmv infection, has not previously been examined. we have cloned and characterized 17 novel mirnas that originate from at least 12 precursor mirnas in mcmv and are not homologous to hcmv mirnas. in parallel, we applied a computational an ... | 2007 | 17928340 |
| ifn-alphabeta-mediated inflammatory responses and antiviral defense in liver is tlr9-independent but myd88-dependent during murine cytomegalovirus infection. | chemokine responses critical for inflammation and promotion of effective innate control of murine cmv (mcmv) in liver have been shown to be dependent on immunoregulatory functions elicited by ifn-alphabeta. however, it remains to be determined whether upstream factors that promote viral sensing resulting in the rapid secretion of ifn-alphabeta in liver differ from those described in other tissues. because plasmacytoid dendritic cells (pdcs) are known producers of high levels of systemic ifn-alph ... | 2007 | 17947693 |
| dominant-negative fadd rescues the in vivo fitness of a cytomegalovirus lacking an antiapoptotic viral gene. | genes that inhibit apoptosis have been described for many dna viruses. herpesviruses often contain even more than one gene to control cell death. apoptosis inhibition by viral genes is postulated to contribute to viral fitness, although a formal proof is pending. to address this question, we studied the mouse cytomegalovirus (mcmv) protein m36, which binds to caspase-8 and blocks death receptor-induced apoptosis. the growth of mcmv recombinants lacking m36 (deltam36) was attenuated in vitro and ... | 2008 | 18094168 |
| murine cytomegalovirus infection and apoptosis in organotypic retinal cultures. | an organotypic retinal culture model was used to determine the pattern of murine cytomegalovirus (mcmv) infection and whether apoptosis is induced in mcmv-infected cultured retinas. | 2008 | 18172106 |
| protective immunization against murine cytomegalovirus infection using adenoviruses and poxviruses expressing hepatitis b virus chimeras. | recombinant adenoviruses, poxviruses, and plasmid dna vaccines encoding different hepatitis b virus (hbv)/murine cytomegalovirus (mcmv) protein chimeras were used to immunize mice. processing of the chimeras resulted in presentation of a protective ld/cd8+ t-cell epitope of the immediate early 1 protein pp89 (ie1 pp89) of mcmv to the immune system. different levels of immunogenicity were observed depending on: (i) the type of viral vector used, (ii) whether the antigens were included in the cell ... | 2007 | 18228223 |
| murine cytomegalovirus regulation of nkg2d ligands. | human cytomegalovirus (hcmv) is a ubiquitous pathogen that causes morbidity risk in immunologically suppressed and immunodeficient patients including congenital infections. approaches to curb the consequences of hcmv infections are restricted by a lack of complete understanding of viral pathogenesis. the infection of mice with murine cytomegalovirus (mcmv) as a model of hcmv infection has been particularly useful in elucidating the role of innate and adaptive immune response mechanisms. a large ... | 2008 | 18259774 |
| the salivary glands as a privileged site of cytomegalovirus immune evasion and persistence. | the salivary glands (sg) provide a haven for persistent cytomegalovirus replication, and in this regard are a privileged site of virus immune evasion. the murine cytomegalovirus (mcmv) model has provided insight into the immunological environment of the sg and the unqiue virus-host relationship of this organ. in response to mcmv infection, a robust t cell-mediated immune response is elicited, comprised predominantly of cd8+ t cells that phenotypically and functionally appear activated. however, ... | 2008 | 18259775 |
| differences between mouse and human cytomegalovirus interactions with their respective hosts at immediate early times of the replication cycle. | the promise of the mouse model of cytomegalovirus (cmv) research lies in a cost effective way to obtain significant data in in vivo settings. keeping that promise requires a high degree of equivalency in the human and mouse virus. while genomic structure and many common proteins suggest that this system is appropriate to develop and test concepts in an organismal context, areas of difference have not been evaluated. here we show that the major immediate early protein 1 (ie1) in mcmv binds the re ... | 2008 | 18264718 |
| conditional gene expression systems to study herpesvirus biology in vivo. | cytomegalovirus (cmv), a prototypic beta-herpesvirus, is an important human pathogen causing protean clinical manifestations in immature and immunocompromised patients. mechanisms of infection can be studied in a mouse model. mouse cytomegalovirus (mcmv) resembles in pathogenesis its human counterpart in many ways. although mcmv infection is studied extensively on the level of organs, the contribution of specific cell types to viral replication in vivo is still elusive. here we describe our appr ... | 2008 | 18324415 |
| mhc class i immune evasion in mcmv infection. | murine cytomegalovirus (mcmv) is a well-studied model of natural beta-herpesvirus infection. however, many questions remain regarding its control by and evasion of the immune response it generates. cd8 and cd4 t cells have both unique and redundant roles in control of the virus that differ based on the immunocompetence of the infected mice. mcmv encodes major histocompatibility complex (mhc) class i immune evasion genes that can have an impact in vitro, but their role in infection of immunocompe ... | 2008 | 18330598 |
| the early kinetics of cytomegalovirus-specific cd8+ t-cell responses are not affected by antigen load or the absence of perforin or gamma interferon. | both innate and adaptive immune responses participate in the control of murine cytomegalovirus (mcmv) infection. in some mouse strains, like balb/c, the control of infection relies on the activities of cd8(+) t cells. mcmv-specific cd8(+) t-cell responses are unusual in that, even after mcmv has been controlled in the periphery, the numbers of circulating virus-specific cd8(+) t cells remain high compared to those observed in other viral infections. to better understand the generation and mainte ... | 2008 | 18337574 |
| epitope-specific in vivo protection against cytomegalovirus disease by cd8 t cells in the murine model of preemptive immunotherapy. | preclinical research in murine models as well as subsequent clinical trials have concordantly revealed a high protective potential of antiviral cd8 t cells, of donor-derived ex vivo memory cd8 t cells in particular, in the immunotherapy of cytomegalovirus (cmv) infection in immunocompromised recipients. although it is generally held view that the observed beneficial effect of the transferred cells is viral epitope-specific, involving the recognition of mhc class-i presented peptides by cognate t ... | 2008 | 18340461 |
| complete nucleotide sequence of a maize chlorotic mottle virus isolate from nebraska. | the complete genome of a maize chlorotic mottle virus isolate from nebraska (mcmv-ne) was cloned and sequenced. the mcmv-ne genome consists of 4,436 nucleotides and shares 99.5 nucleotide sequence identity with an mcmv isolate from kansas (mcmv-ks). of 22 polymorphic sites, most resulted from transition with a clear bias for u to c and c to u substitutions. the mcmv-ne genome was assembled into a single plasmid insert and used as a template to transcribe rna in vitro. as rna transcribed from the ... | 2008 | 18365127 |
| subdominant cd8 t-cell epitopes account for protection against cytomegalovirus independent of immunodomination. | cytomegalovirus (cmv) infection continues to be a complication in recipients of hematopoietic stem cell transplantation (hsct). preexisting donor immunity is recognized as a favorable prognostic factor for the reconstitution of protective antiviral immunity mediated primarily by cd8 t cells. furthermore, adoptive transfer of cmv-specific memory cd8 t (cd8-t(m)) cells is a therapeutic option for preventing cmv disease in hsct recipients. given the different cmv infection histories of donor and re ... | 2008 | 18367531 |
| dissection of the antiviral nk cell response by mcmv mutants. | our understanding of virus control by natural killer (nk) cells relies mainly on in vitro observations. the significance of these findings for virus control in vivo is not yet fully understood. complexity is added by the fact that many viruses, particularly herpesviruses, are equipped with sets of genes that, dependent on the genetic background of the host, modify the nk cell response. the advent of recombinant dna technology and mutagenesis procedures for bac-cloned viral genomes has made it po ... | 2008 | 18370152 |
| testing human biologicals in animal host resistance models. | the purpose of immunotoxicity testing is to obtain data that is meaningful for safety assessment. host resistance assays are the best measure of a toxicant's effect on the overall ability to mount an effective immune response and protect the host from infectious disease. an outline is presented for immunotoxicological evaluation using host resistance assays. the influenza virus host resistance model is useful to evaluate the overall health of the immune system and is one of the most thoroughly c ... | 2008 | 18382855 |
| laboratory strains of murine cytomegalovirus are genetically similar to but phenotypically distinct from wild strains of virus. | murine cytomegalovirus (mcmv) is widely used to model human cytomegalovirus (hcmv) infection. however, it is known that serially passaged laboratory strains of hcmv differ significantly from recently isolated clinical strains of hcmv. it is therefore axiomatic that clinical models of hcmv using serially passaged strains of mcmv may not be able to fully represent the complexities of the system they are attempting to model and may not fully represent the complex biology of mcmv. to determine wheth ... | 2008 | 18417589 |
| mouse cytomegalovirus inhibits beta interferon (ifn-beta) gene expression and controls activation pathways of the ifn-beta enhanceosome. | we have investigated beta interferon (ifn-beta) and ifn-alpha4 gene expression and activation of related transcription factors in mouse cytomegalovirus (mcmv)-infected fibroblasts. mrna analysis demonstrated an initial phase of ifn gene induction upon mcmv infection, which was followed by a sustained mcmv-mediated simultaneous downregulation of ifn-beta and ifn-alpha4 gene expression. the induction of ifn transcription resulted from the activation of the components of the ifn-beta enhanceosome, ... | 2008 | 18420790 |
| cutting edge: overlapping functions of tlr7 and tlr9 for innate defense against a herpesvirus infection. | as initially demonstrated with murine cytomegalovirus (mcmv), plasmacytoid dendritic cells (pdcs) are the major source of ifn-alpha/beta in response to a variety of viruses in vivo. however, contradictory results have been obtained pertaining to the mechanisms promoting ifn-alpha/beta production by pdcs in response to mcmv. in this study we show that tlr7 and tlr9 exert redundant functions for ifn-alpha/beta, il-12p40, and tnf-alpha production by pdcs in vivo during mcmv infection. in contrast, ... | 2008 | 18424698 |
| a mouse model for cytomegalovirus infection. | this unit describes procedures for infecting newborn and adult mice with murine cytomegalovirus (mcmv). methods are included for propagating mcmv in cell cultures and for preparing a more virulent form of mcmv from salivary glands of infected mice. a plaque-forming cell (pfc) assay is provided for measuring mcmv titers of infected tissues or virus stocks. in addition, a method is described for preparing the murine embryonic fibroblasts used for propagating mcmv and for the pfc assay. | 2001 | 18432758 |