Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
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| 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 |
| g protein-coupled receptor (gpcr) kinase 2 regulates agonist-independent gq/11 signaling from the mouse cytomegalovirus gpcr m33. | the mouse cytomegalovirus m33 protein is highly homologous to mammalian g protein-coupled receptors (gpcrs) yet functions in an agonist-independent manner to activate a number of classical gpcr signal transduction pathways. m33 is functionally similar to the human cytomegalovirus-encoded us28 gpcr in its ability to induce inositol phosphate accumulation, activate nf-kappab, and promote smooth muscle cell migration. this ability to promote cellular migration suggests a role for viral gpcrs like m ... | 2006 | 17088245 |
| murine cytomegalovirus encodes a stable intron that facilitates persistent replication in the mouse. | the human cytomegalovirus immediate-early 5-kb rna previously has been shown to be a stable intron that is not required for efficient replication of the virus in cultured fibroblasts. here we describe a murine cytomegalovirus 7.2-kb ortholog of the human cytomegalovirus 5-kb rna. the 5' end of the 7.2-kb transcript maps to a consensus splice-donor site that is conserved among all cytomegaloviruses. we constructed mutant viruses lacking the entire 7.2-kb coding domain, the splice-donor site predi ... | 2006 | 17105807 |
| 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 |
| critical residues at the ly49 natural killer receptor's homodimer interface determine functional recognition of m157, a mouse cytomegalovirus mhc class i-like protein. | nk cell function is regulated by ly49 receptors in mice and killer cell ig-like receptors in humans. although inhibitory ly49 and killer cell ig-like receptors predominantly ligate classical mhc class i molecules, recent studies suggest that their activating counterparts recognize infection. the quintessential example is resistance to the mouse cmv in c57bl/6 mice, which depends on the functional recognition of m157, a mouse cmv-encoded mhc class i-like molecule, by ly49h, an activating nk cell ... | 2007 | 17182575 |
| cytomegalovirus primary envelopment occurs at large infoldings of the inner nuclear membrane. | we have investigated the morphogenesis of human and murine cytomegalovirus by transmission electron microscopy after high-pressure freezing, freeze substitution, and plastic embedding. we observed large tubular infoldings of the inner nuclear membrane that were free of lamina and active in primary envelopment and subsequent transport of capsids to the nuclear periphery. semiquantitative determinations of the enlarged inner nuclear membrane area and the location of the primary envelopment of nucl ... | 2007 | 17192309 |
| 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 |
| rat cytomegalovirus gene expression in cardiac allograft recipients is tissue specific and does not parallel the profiles detected in vitro. | rat cytomegalovirus (rcmv) is a beta-herpesvirus with a 230-kbp genome containing over 167 open reading frames (orfs). rcmv gene expression is tightly regulated in cultured cells, occurring in three distinct kinetic classes (immediate early, early, and late). however, the extent of viral-gene expression in vivo and its relationship to the in vitro expression are unknown. in this study, we used rcmv-specific dna microarrays to investigate the viral transcriptional profiles in cultured, rcmv-infec ... | 2007 | 17251289 |
| chronic gvhd decreases antiviral immune responses in allogeneic bmt. | chronic graft-versus-host disease (cgvhd) is associated with functional immunodeficiency and an increased risk of opportunistic infections in allogeneic bone marrow transplantation (bmt). we used a parent to f1 model of allogeneic bmt to test the hypothesis that cgvhd leads to impaired antigen-specific antiviral immunity and compared bm transplant recipients with cgvhd to control groups of allogeneic bm transplant recipients without gvhd. mice with and without cgvhd received a nonlethal dose of ... | 2007 | 17289817 |
| 20s proteasome-dependent generation of an iepp89 murine cytomegalovirus-derived h-2l(d) epitope from a recombinant protein. | the majority of mhc class i epitopes is generated through the ubiquitin-proteasome system. in the present study, we have analyzed the proteasome-dependent generation of the ie pp89 mcmv-derived h-2l(d) epitope by both in vitro and in vivo experiments. as revealed by cytotoxic t-cell assays, the pp89 9mer epitope was generated with high fidelity from the recombinant ie pp89 by 20s proteasomes. in vitro processing showed that the recombinant pp89 was rapidly degraded by 20s proteasomes. analysis o ... | 2007 | 17303071 |
| a flow cytometry-based method for detecting antibody responses to murine cytomegalovirus infection. | an assay based on target cells infected with green fluorescent protein labeled murine cytomegalovirus (gfp-mcmv) and dual color flow cytometry for detecting antibody to mcmv is described. after optimizing conditions for this technique, kinetics of anti-mcmv igg antibody response was tested in susceptible (balb/c) and resistant (c57bl/6) mouse strains following primary mcmv infection. previously published antibody kinssetics were confirmed in susceptible mice, with peak igg response seen approxim ... | 2007 | 17303259 |
| 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 |
| molecular mapping of autoimmune b cell responses in experimental myocarditis. | autoimmune responses directed against heart-specific antigens most likely play a key role in the pathogenesis of myocarditis. although autoantibodies against cardiac determinants are frequently detected both in human patients and mice suffering from myocarditis, the immunological mechanisms for their induction have not yet been fully explored. we used here the serex approach (serological identification of recombinantly expressed proteins) to molecularly dissect heart-specific autoimmune b cell r ... | 2007 | 17336498 |
| transplacental murine cytomegalovirus infection in the brain of scid mice. | congenital cytomegalovirus (cmv) infection is the most common congenital viral infection in humans and the major nonhereditary cause of central nervous system (cns) developmental disorders. previous attempts to develop a murine cmv (mcmv) model of natural congenital human cmv (hcmv) infection have failed because mcmv does not cross the placenta in immunocompetent mice. | 2007 | 17349048 |
| structure of a herpesvirus-encoded cysteine protease reveals a unique class of deubiquitinating enzymes. | all members of the herpesviridae contain within their large tegument protein a cysteine protease module that displays deubiquitinating activity. we report the crystal structure of the cysteine protease domain of murine cytomegalovirus m48 (m48(usp)) in a complex with a ubiquitin (ub)-based suicide substrate. m48(usp) adopts a papain-like fold, with the active-site cysteine forming a thioether linkage to the suicide substrate. the ub core participates in an extensive hydrophobic interaction with ... | 2007 | 17349955 |
| transcriptional reactivation of murine cytomegalovirus ie gene expression by 5-aza-2'-deoxycytidine and trichostatin a in latently infected cells despite lack of methylation of the major immediate-early promoter. | we have used a spleen explant model to investigate mechanisms of murine cytomegalovirus latency and reactivation. induction of immediate-early (ie) gene expression occurs in explants after approximately 9 days in culture and virus reactivation follows induction of ie gene expression with kinetics similar to that of productive infection in vitro. this occurs independently of tnf receptor signalling. treatment with the dna methylation inhibitor 5-aza-2'-deoxycytidine and the histone deacetylase in ... | 2007 | 17374752 |
| random screening for dominant-negative mutants of the cytomegalovirus nuclear egress protein m50. | inactivation of gene products by dominant-negative (dn) mutants is a powerful tool to assign functions to proteins. here, we present a two-step procedure to establish a random screen for dn alleles, using the essential murine cytomegalovirus gene m50 as an example. first, loss-of-function mutants from a linker-scanning library were tested for inhibition of virus reconstitution with the help of flp-mediated ectopic insertion of the mutants into the viral genome. second, dn candidates were confirm ... | 2007 | 17376929 |
| a role for natural killer t cells and cd1d molecules in counteracting suppression of hematopoiesis in mice induced by infection with murine cytomegalovirus. | infection of immunocompromised patients with cytomegalovirus (cmv), such as that occurring in patients undergoing hematopoietic stem cell transplantation, is a serious clinical problem. cmv infection has been reported to suppress hematopoiesis. in immunocompetent hosts cmv is controlled initially by the innate immune system, with cd1d molecules and natural killer t (nkt) cells playing a role in the antiviral immune response in several model systems. we hypothesized that cd1d and nkt cells are in ... | 2007 | 17379092 |
| tumor necrosis factor-alpha-induced apoptosis in murine cytomegalovirus retinitis. | previous results suggest that apoptosis is involved in the pathogenesis of murine cytomegalovirus (mcmv) retinitis. to explore the mechanism underlying retinal apoptosis in mcmv retinitis, this study was initiated to determine whether the tumor necrosis factor receptor (tnfr)1-tnf pathway is involved in apoptosis during mcmv retinitis. | 2007 | 17389501 |
| endogenous glucocorticoids protect against tnf-alpha-induced increases in anxiety-like behavior in virally infected mice. | endogenous glucocorticoids restrain proinflammatory cytokine responses to immune challenges such as viral infection. in addition, proinflammatory cytokines induce behavioral alterations including changes in locomotor/exploratory activity. accordingly, we examined proinflammatory cytokines and open-field behavior in virally infected mice rendered glucocorticoid deficient by adrenalectomy (adx). mice were infected with murine cytomegalovirus (mcmv), and open-field behavior (36 h post-infection) an ... | 2007 | 17389906 |
| 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 |
| 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 |
| pathogenesis and antibody response to a cytomegalovirus infection in newborn rats. | the present study described the kinetics of rat cytomegalovirus (rcmv) infection in newborn rats by monitoring infectious virus and viral antigens in various organs, viral dna in the blood (dnaemia) and antibody response. these parameters were evaluated quantitatively using double-antibody sandwich elisa (das-elisa), real-time pcr, indirect elisa and virus infectivity assay. for the first time das-elisa was used for detection of rcmv antigen directly from organ samples. the relationships between ... | 2007 | 17432941 |
| bystander attenuation of neuronal and astrocyte intercellular communication by murine cytomegalovirus infection of glia. | astrocytes are the first cells infected by murine cytomegalovirus (mcmv) in primary cultures of brain. these cells play key roles in intercellular signaling and neuronal development, and they modulate synaptic activity within the nervous system. using ratiometric fura-2 digital calcium imaging of >8,000 neurons and glia, we found that mcmv-infected astrocytes showed an increase in intracellular basal calcium levels and an enhanced response to neuroactive substances, including glutamate and atp, ... | 2007 | 17459923 |
| cytomegalovirus evasion of innate immunity by subversion of the nkr-p1b:clr-b missing-self axis. | cytomegaloviruses are known to encode several gene products that function to subvert mhc-dependent immune recognition. here we characterize a rat cytomegalovirus (rcmv) c-type lectin-like (rctl) gene product with homology to the clr ligands for the nkr-p1 receptors. rcmv infection rapidly extinguished host clr-b expression, thereby sensitizing infected cells to killing by natural killer (nk) cells. however, the rctl protein functioned as a decoy ligand to protect infected cells from nk killing v ... | 2007 | 17462921 |
| cytomegalovirus exploits il-10-mediated immune regulation in the salivary glands. | the salivary glands represent a major site of cytomegalovirus replication and transmission to other hosts. despite control of viral infection by strong t cell responses in visceral organs cytomegalovirus replication continues in the salivary glands of mice, suggesting that the virus exploits the mucosal microenvironment. here, we show that t cell immunity in the salivary glands is limited by the induction of cd4 t cells expressing the regulatory cytokine interleukin (il)-10. blockade of il-10 re ... | 2007 | 17485516 |
| herpesvirus latency confers symbiotic protection from bacterial infection. | all humans become infected with multiple herpesviruses during childhood. after clearance of acute infection, herpesviruses enter a dormant state known as latency. latency persists for the life of the host and is presumed to be parasitic, as it leaves the individual at risk for subsequent viral reactivation and disease. here we show that herpesvirus latency also confers a surprising benefit to the host. mice latently infected with either murine gammaherpesvirus 68 or murine cytomegalovirus, which ... | 2007 | 17507983 |
| 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 |
| structural elucidation of the m157 mouse cytomegalovirus ligand for ly49 natural killer cell receptors. | natural killer (nk) cells express activating and inhibitory receptors that, in concert, survey cells for proper expression of cell surface major histocompatibility complex (mhc) class i molecules. the mouse cytomegalovirus encodes an mhc-like protein, m157, which is the only known viral antigen to date capable of engaging both activating (ly49h) and inhibitory (ly49i) nk cell receptors. we have determined the 3d structure of m157 and studied its biochemical and cellular interactions with the ly4 ... | 2007 | 17537914 |
| cyclosporine inhibits mouse cytomegalovirus infection via a cyclophilin-dependent pathway specifically in neural stem/progenitor cells. | the potential of neural stem and progenitor cell (nspc) transplantation in neurodegenerative disease raises a concern about immunosuppressive agents and opportunistic neurotropic pathogens that may interfere with engraftment. cytomegalovirus (cmv) is an important opportunistic pathogen infecting the central nervous system, where it may remain latent for life, following transplacental transmission. cyclosporine (cs), an immunosuppressive drug used in organ transplantation, where its use is associ ... | 2007 | 17553872 |
| cytomegalovirus primary envelopment at large nuclear membrane infoldings: what's new? | 2007 | 17567708 | |
| 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 |
| 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 |
| ox40 costimulation promotes persistence of cytomegalovirus-specific cd8 t cells: a cd4-dependent mechanism. | the mechanisms that regulate cmv-specific t cell responses in vivo are poorly understood. during murine cmv infection of b6 mice, primary responses in the spleen are dominated by cd8 t cells reactive with antigenic epitopes in m45, m57, and m139 murine cmv gene products. however, during the later persistent phase of infection, cd8 t cell responses to epitopes in m139 and m38 viral gene products predominate. the basis for this shift in cd8 t populations is unknown. in this study, we demonstrate t ... | 2007 | 17675479 |
| engineering of cytomegalovirus genomes for recombinant live herpesvirus vaccines. | the advances of sequence knowledge and genetic engineering hold a great promise for a rational approach to vaccine development. herpesviruses are important pathogens of all vertebrates. they cause acute and chronic infections and persist in their hosts for life. in man there are eight herpesviruses known and most of them can be linked to diseases. to date only one licensed vaccine against a human herpesvirus exists and there is no proven successful concept on rational design for herpesvirus vacc ... | 2008 | 17702650 |
| natural killer cells promote early cd8 t cell responses against cytomegalovirus. | understanding the mechanisms that help promote protective immune responses to pathogens is a major challenge in biomedical research and an important goal for the design of innovative therapeutic or vaccination strategies. while natural killer (nk) cells can directly contribute to the control of viral replication, whether, and how, they may help orchestrate global antiviral defense is largely unknown. to address this question, we took advantage of the well-defined molecular interactions involved ... | 2007 | 17722980 |
| thymosin alpha1 activates the tlr9/myd88/irf7-dependent murine cytomegalovirus sensing for induction of anti-viral responses in vivo. | reactivation of latent human cytomegalovirus following allogeneic transplantation is a major cause of morbidity and mortality and predisposes to severe complications. thymosin alpha1 (talpha1), a naturally occurring thymic peptide, is approved for treatment of some viral infections and as an immune adjuvant. talpha1 successfully primed dendritic cells (dcs) for anti-microbial t helper type 1 resistance through toll-like receptor (tlr) 9 signaling. we sought to determine here whether talpha1 coul ... | 2007 | 17804687 |
| 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 |
| quantitative investigation of murine cytomegalovirus nucleocapsid interaction. | in this study, we quantitatively investigate the role of the m97 protein for viral morphogenesis in murine cytomegalovirus (mcmv)-infected fibroblast cells. for this purpose, a statistical analysis is performed for the spatial distribution of nuclear b-capsids (devoid of dna, containing the scaffold) and c-capsids (filled with dna). cell nuclei infected with either wild-type or an m97 deletion mutant were compared. univariate and multivariate point process characteristics (like ripley's k-functi ... | 2007 | 17910700 |
| 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 |
| the impact of regulatory t cells on t-cell immunity following hematopoietic cell transplantation. | regulatory t cells (tregs) prevent graft-versus-host disease (gvhd) by inhibiting the proliferation and function of conventional t cells (tcons). however, the impact of tregs on t-cell development and immunity following hematopoietic cell transplantation (hct) is unknown. using a murine gvhd model induced by tcons, we demonstrate that adoptive transfer of tregs leads to (1) abrogration of gvhd, (2) preservation of thymic and peripheral lymph node architecture, and (3) an accelerated donor lympho ... | 2008 | 17916743 |
| 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 |
| mouse cytomegalovirus micrornas dominate the cellular small rna profile during lytic infection and show features of posttranscriptional regulation. | micrornas (mirnas) are small, noncoding rna molecules that regulate gene expression at the posttranscriptional level. originally identified in a variety of organisms ranging from plants to mammals, mirnas have recently been identified in several viruses. viral mirnas may play a role in modulating both viral and host gene expression. here, we report on the identification and characterization of 18 viral mirnas from mouse fibroblasts lytically infected with the murine cytomegalovirus (mcmv). the m ... | 2007 | 17942535 |
| murine cytomegalovirus open reading frame m29.1 augments virus replication both in vitro and in vivo. | murine cytomegalovirus mutant rc29, with a premature stop codon mutation in the m29 open reading frame (orf), produced no apparent phenotype in cell culture or following infection of balb/c mice. in contrast, a similar mutant virus, rc29.1, with a premature stop codon mutation in its m29.1 orf, showed reduced virus yields (2-3 log(10) p.f.u. ml(-1)) in tissue culture. mutant virus yields in balb/c mice were delayed, reduced ( approximately 1 log(10) p.f.u. per tissue) and persisted less well in ... | 2007 | 17947515 |
| 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 |
| individual plasmacytoid dendritic cells are major contributors to the production of multiple innate cytokines in an organ-specific manner during viral infection. | plasmacytoid dendritic cells (pdcs) are an important source of ifn-alpha/beta in response to a variety of viruses in vivo, including murine cytomegalovirus (mcmv). however, the respective contributions of various infected organs, and within these of pdcs, conventional dendritic cells and other cells, to the systemic production of ifn-alpha/beta or other innate cytokines during viral infections in vivo is largely unknown. whether a specialization of pdc subsets in the production of different patt ... | 2008 | 18000008 |
| increased weight loss with reduced viral replication in interleukin-10 knock-out mice infected with murine cytomegalovirus. | the anti-inflammatory cytokine interleukin (il)-10 plays an important role in the regulation of host-immune responses. here we studied the role il-10 plays in host responses to cytomegalovirus (cmv) infection. we demonstrate that manifestations of murine cmv (mcmv) disease are more severe in il-10 knock-out mice, despite significantly reduced levels of viral replication. cytokine analysis of serum revealed increased levels of interferon (ifn)-gamma, monocyte chemotactic protein 1 (mcp-1) and il- ... | 2008 | 18005264 |
| functional analysis of the murine cytomegalovirus chemokine receptor homologue m33: ablation of constitutive signaling is associated with an attenuated phenotype in vivo. | the murine cytomegalovirus (mcmv) m33 gene is conserved among all betaherpesviruses and encodes a homologue of seven-transmembrane receptors (7tmr) with the capacity for constitutive signaling. previous studies have demonstrated that m33 is important for mcmv dissemination to or replication within the salivary glands. in this study, we probed n- and c-terminal regions of m33 as well as known 7tmr signature motifs in transmembrane (tm) ii and tm iii to determine the impact on cell surface express ... | 2008 | 18057236 |
| 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 |
| t cell acquisition of apc membrane can impact interpretation of adoptive transfer experiments using cd45 congenic mouse strains. | congenic mouse strains bearing allelic variants of cd45 are often used in adoptive transfer experiments. here, we report that immune cd8(+) splenocytes of donor origin acquired the recipient's congenic cd45 marker during interaction with antigen-bearing cells, presumably as a result of membrane transfer upon dissolution of the immunological synapse. acquisition of recipient marker by donor cells was most prominent after in vitro incubation with peptide for intracellular cytokine staining, where ... | 2008 | 18178216 |
| cytomegalovirus inhibition of embryonic mouse tooth development: a model of the human amelogenesis imperfecta phenocopy. | cytomegalovirus (cmv) is one of the most common causes of major birth defects in humans. of the approximately 8400 children born each year in the u.s. with cmv-induced birth defects, more than 1/3 of these children exhibit hypoplasia and hypocalcification of tooth enamel. our objective was to initiate the investigation of the pathogenesis of cmv-induced tooth defects. | 2008 | 18201685 |
| immune evasion of natural killer cells by viruses. | natural killer (nk) cells are important in the host resistance to viral infections. they are among the first cells to sense the release of proinflammatory cytokines, as well as the downregulation of surface mhc class i molecules and molecules induced by viral invasion of cells. various viral functions have evolved to counter nk cell responses illustrating the evolutionary struggles between viruses and nk cells. ligands for nk cell receptors are primary targets for viral immunoevasion. in order t ... | 2008 | 18206359 |
| two novel nkg2d ligands of the mouse h60 family with differential expression patterns and binding affinities to nkg2d. | h60, originally described as a dominant minor histocompatibility ag, is an mhc class i-like molecule that serves as a ligand for the nkg2d receptor. in the present study, we identified two novel mouse chromosome 10-encoded nkg2d ligands structurally resembling h60. these ligands, which we named h60b and h60c, encode mhc class i-like molecules with two extracellular domains. whereas h60b has a transmembrane region, h60c is a gpi-anchored protein. recombinant soluble h60b and h60c proteins bound t ... | 2008 | 18209064 |
| 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 |
| phenotypes of major immediate-early gene mutants of mouse cytomegalovirus. | immediate-early (ie) genes are the first genes to be transcribed during the lytic replication cycle of cytomegaloviruses (cmv), and encode nonstructural proteins, which are assumed to have mainly regulatory functions. the ie proteins may play important roles in the pathogenesis of cmv in vivo, for instance during the establishment of latency and during reactivation. we constructed mouse cmv mutants with disruptions in the major ie genes, ie1 and ie3, to study the roles of these genes in the cont ... | 2008 | 18239940 |
| adoptive cd8 t cell control of pathogens cannot be improved by combining protective epitope specificities. | adoptive transfer of cd8 t cells has the potential to cure infectious or malignant diseases that are refractory to conventional chemotherapy. a practically important but still unanswered question is whether mixtures of protective cd8 t cells with different epitope specificities mediate more efficient effector cell functions than do the monospecific individual cd8 t cell populations. in this study, we have addressed this issue for models of viral and bacterial infection. cd8 t cell-mediated cytot ... | 2008 | 18240950 |
| murine cytomegalovirus influences foxj1 expression, ciliogenesis, and mucus plugging in mice with allergic airway disease. | we have followed throughout time the development of allergic airway disease (aad) in both uninfected mice and mice infected intranasally with murine cytomegalovirus (mcmv). histological evaluation of lung tissue from uninfected mice with aad demonstrated mucus plugging after 14 and 21 days of ovalbumin-aerosol challenge, with resolution of mucus plugging occurring by 42 days. in mcmv/aad mice, mucus plugging was observed after 7 days of ovalbumin-aerosol challenge and remained present at 42 days ... | 2008 | 18258850 |
| 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 |
| altered development of the brain after focal herpesvirus infection of the central nervous system. | human cytomegalovirus infection of the developing central nervous system (cns) is a major cause of neurological damage in newborn infants and children. to investigate the pathogenesis of this human infection, we developed a mouse model of infection in the developing cns. intraperitoneal inoculation of newborn animals with murine cytomegalovirus resulted in virus replication in the liver followed by virus spread to the brain. virus infection of the cns was associated with the induction of inflamm ... | 2008 | 18268036 |
| atf3 regulates mcmv infection in mice by modulating ifn-gamma expression in natural killer cells. | activating transcription factor 3 (atf3) is a negative regulator of proinflammatory cytokine expression in macrophages, and atf3-deficient mice are more susceptible to endotoxic shock. here, we demonstrate that atf3 interacts with a cis-regulatory element of the ifn-gamma gene in natural killer (nk) cells, and that atf3null nk cells show increased transcription and secretion of ifn-gamma. nk cell-derived ifn-gamma has previously been demonstrated to be protective against murine cytomegalovirus ( ... | 2008 | 18268321 |
| type i interferon response to cytomegalovirus infection: the kick-start. | host responses to cytomegalovirus infection include initial early production of alpha and beta interferons, also called type i interferons, which are elicited directly by viral products via toll-like receptors. new data indicate that, preceding these events, an earlier critical type i interferon elicited in primary infected stromal cells via the lymphotoxin beta receptor system and mediated by b cells is necessary to kick-start an efficient antiviral response. | 2008 | 18312838 |
| lymphotoxin-mediated crosstalk between b cells and splenic stroma promotes the initial type i interferon response to cytomegalovirus. | toll-like receptor (tlr)-dependent pathways control the production of ifnalphabeta, a key cytokine in innate immune control of viruses including mouse cytomegalovirus (mcmv). the lymphotoxin (lt) alphabeta-ltbeta receptor signaling pathway is also critical for defense against mcmv and thought to aid in the ifnbeta response. we find that upon mcmv infection, mice deficient for lymphotoxin (lt)alphabeta signaling cannot mount the initial part of a biphasic ifnalphabeta response, but show normal le ... | 2008 | 18312841 |
| murine cytomegalovirus m38.5 protein inhibits bax-mediated cell death. | many viruses encode proteins that inhibit the induction of programmed cell death at the mitochondrial checkpoint. murine cytomegalovirus (mcmv) encodes the m38.5 protein, which localizes to mitochondria and protects human hela cells and fibroblasts from apoptosis triggered by proteasome inhibitors but not from fas-induced apoptosis. however, the ability of this protein to suppress the apoptosis of murine cells and its role during mcmv infection have not been investigated previously. here we show ... | 2008 | 18321965 |
| 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 |
| effect of oral treatment with (s)-hpmpa, hdp-(s)-hpmpa or ode-(s)-hpmpa on replication of murine cytomegalovirus (mcmv) or human cytomegalovirus (hcmv) in animal models. | we utilized balb/c mice infected with murine cmv (mcmv) or severe combined immunodeficient (scid) mice implanted with human fetal tissue and infected with hcmv to determine the efficacy of (s)-9-[3-hydroxy-2-(phophonomethoxy)propyl]adenine ((s)-hpmpa), hexadecyloxypropyl-(s)-hpmpa (hdp-(s)-hpmpa) or octadecyloxyethyl-(s)-hpmpa (ode-(s)-hpmpa). in mcmv-infected balb/c mice, oral hdp-(s)-hpmpa at 30 mg/kg significantly reduced mortality when started 24-48 h post inoculation. in the experimental hc ... | 2008 | 18336926 |
| 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 |
| correlation of dendritic cell maturation and the formation of aggregates of poly-ubiquitinated proteins in the cytosol. | dendritic cells (dcs) are the most powerful antigen presenting cells (apcs) in the immune system. therefore, they are able to take up antigen by phagocytosis, macropinocytosis or endocytosis, process it in the cytosol and present it to naive t cells. it is known that presentation of the immunodominant influenza virus nucleoprotein-derived ctl epitope is delayed in bone marrow-derived dcs (bmdcs) compared to non-professional apcs. this delay coincided with the formation of transient aggregations ... | 2008 | 18340462 |
| 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 |
| enu mutagenesis in mice. | forward genetics has led to many "breakthrough" discoveries, and with the mouse genome almost fully sequenced, the creation of phenotypes through random germline mutagenesis has become an efficient means by which to find the function of yet undescribed genes. in this chapter, we will provide a practical guideline for performing germline mutagenesis in mice. in particular, we will focus on the application of this technology to identify genes that are essential to innate immune defense. | 2008 | 18370145 |
| 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 |
| cytomegalovirus induces abnormal chondrogenesis and osteogenesis during embryonic mandibular development. | human clinical studies and mouse models clearly demonstrate that cytomegalovirus (cmv) disrupts normal organ and tissue development. although cmv is one of the most common causes of major birth defects in humans, little is presently known about the mechanism(s) underlying cmv-induced congenital malformations. our prior studies have demonstrated that cmv infection of first branchial arch derivatives (salivary glands and teeth) induced severely abnormal phenotypes and that cmv has a particular tro ... | 2008 | 18371224 |
| (c)re-combining textbook models of virus spread within the host. | classic viral pathogenesis models postulate that tissues supporting efficient virus replication promote virus dissemination, which culminates in clinical illness. in this issue of cell host & microbe, sacher and colleagues use cre/loxp recombination to label murine cytomegalovirus during replication in distinct cell types in vivo. strikingly, they demonstrate that the most productive cell type in the host-the hepatocyte-contributes no progeny to dissemination to other tissues. | 2008 | 18407062 |
| the major virus-producing cell type during murine cytomegalovirus infection, the hepatocyte, is not the source of virus dissemination in the host. | the course of systemic viral infections is determined by the virus productivity of infected cell types and the efficiency of virus dissemination throughout the host. here, we used a cell-type-specific virus labeling system to quantitatively track virus progeny during murine cytomegalovirus infection. we infected mice that expressed cre recombinase selectively in vascular endothelial cells or hepatocytes with a murine cytomegalovirus for which cre-mediated recombination would generate a fluoresce ... | 2008 | 18407069 |
| 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 |
| roles of neural stem progenitor cells in cytomegalovirus infection of the brain in mouse models. | cytomegalovirus (cmv) is the most significant infectious cause of brain disorders in humans. although the brain is the principal target organ for cmv infection in infants with congenital infection and in immunocompromised patients, little has been known about cellular events in pathogenesis of the brain disorders. mouse models have been developed by the authors for studying the cell tropism, infectious dynamics of cmv infection and the effects of cmv infection on proliferation, regeneration and ... | 2008 | 18429823 |
| 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 |
| cutting edge: murine cytomegalovirus induces a polyfunctional cd4 t cell response. | cd4 t lymphocytes regulate the adaptive immune response to most viruses, both by providing help to cd8 t cells and b cells as well as through direct antiviral activity. currently, no mouse cytomegalovirus (mcmv)-specific cd4 t cell responses are known. in this study, we identify and characterize 15 i-a(b)-restricted cd4 t cell responses specific for mcmv epitopes. cd4 t cells accumulate to high levels in the spleen and lungs during acute infection and produce multiple cytokines (ifn-gamma, tnf, ... | 2008 | 18453564 |
| ly49h+ nk cells migrate to and protect splenic white pulp stroma from murine cytomegalovirus infection. | in this study, we show that in the absence of a protective nk cell response, murine cmv causes destruction of splenic white and red pulp pulp areas in the first few days of infection. destruction of t zone stroma is associated with almost complete loss of dendritic cells and t cells. we provide evidence that the virus replicates in red and white pulp stroma in vivo and in vitro. control of white pulp viral replication is associated with migration of murine cmv-specific activated nk cells to whit ... | 2008 | 18453597 |
| establishment of a cell-based assay for screening of compounds inhibiting very early events in the cytomegalovirus replication cycle and characterization of a compound identified using the assay. | to simplify the detection of infectious human cytomegalovirus (hcmv), we generated a cell line that produced luciferase in a dose-dependent manner upon hcmv infection. using this cell line, we identified anti-hcmv compounds from a diverse library of 9,600 compounds. one of them, 1-(3,5-dichloro-4-pyridyl)piperidine-4-carboxamide (dppc), was effective against hcmv (towne strain) infection of human lung fibroblast cells at a 50% effective concentration of 2.5 microm. dppc also inhibited the growth ... | 2008 | 18458124 |
| preliminary characterization of murine cytomegaloviruses with insertional and deletional mutations in the m34 open reading frame. | a viable virus could not be recovered from a mutant murine cytomegalovirus (mcmv) bac in which the m34 orf had been deleted (bacdeltam34). in contrast, an m34 mutant virus (rcm34), in which the m34 orf was interrupted by transposon insertion at nt 44,827 of the smith mcmv bac, was attenuated in replication both in tissue culture and in scid mice. similarly, mutant virus rc3'deltam34, in which the 3'-end was deleted from nt 44,724 to nt 45,647, produced similar replication kinetics in tissue cult ... | 2008 | 18461610 |
| induction of cytomegalovirus-infected labyrinthitis in newborn mice by lipopolysaccharide: a model for hearing loss in congenital cmv infection. | congenital cytomegalovirus (cmv) infection is the most common infectious cause of sensorineural hearing loss in children. here, we established an experimental model of hearing loss after systemic infection with murine cmv (mcmv) in newborn mice. although almost no viral infection was observed in the inner ears and brains by intraperitoneal (i.p.) infection with mcmv in newborn mice, infection in these regions was induced in combination with intracerebral (i.c.) injection of bacterial lipopolysac ... | 2008 | 18475257 |
| intranasal immunization with recombinant vesicular stomatitis virus expressing murine cytomegalovirus glycoprotein b induces humoral and cellular immunity. | cytomegalovirus is a leading cause of morbidity and mortality among neonatal and immunocompromised patients. the use of vaccine prophylaxis continues to be an effective approach to reducing viral infections and their associated diseases. murine cytomegalovirus (mcmv) has proven to be a valuable animal model in determining the efficacy of newly developed vaccine strategies in vivo. live recombinant vesicular stomatitis viruses (rvsv) have successfully been used as vaccine vectors for several viru ... | 2008 | 18524170 |
| characterization of murine cytomegalovirus m157 from infected cells and identification of critical residues mediating recognition by the nk cell receptor ly49h. | activated nk cells mediate potent cytolytic and secretory effector functions and are vital components of the early antiviral immune response. nk cell activities are regulated by the assortment of inhibitory receptors that recognize mhc class i ligands expressed on healthy cells and activating receptors that recognize inducible host ligands or ligands that are not well characterized. the activating ly49h receptor of mouse nk cells is unique in that it specifically recognizes a virally encoded lig ... | 2008 | 18566392 |
| prior infection with murine cytomegalovirus (mcmv) limits the immunocontraceptive effects of an mcmv vector expressing the mouse zona-pellucida-3 protein. | we have developed a murine cytomegalovirus (mcmv)-vectored vaccine expressing the mouse zona-pellucida-3 gene (rmcmv-zp3), which successfully induces infertility in experimentally inoculated laboratory or wild-derived mice. however, the future success of this vector as a fully disseminating vaccine in free-living mice may be compromised by pre-existing immunity since there is a high prevalence of naturally acquired mcmv infection in these mice. to evaluate the effect of prior immunity to mcmv on ... | 2008 | 18573574 |
| the dynamics of mouse cytomegalovirus-specific cd4 t cell responses during acute and latent infection. | the dynamics of mouse cytomegalovirus (mcmv)-specific cd4 t cell responses and the mechanisms by which these cells contribute to viral control are not well understood, mainly due to lack of appropriate tools to characterize mcmv-specific cd4 t cells. we therefore generated mcmv-specific cd4 t cell hybridomas, then used an mcmv expression library and overlapping peptides to identify cd4 t cell epitopes. we used these novel tools to study the long-term kinetics and organ distribution of mcmv-speci ... | 2008 | 18606665 |
| continuous engagement of a self-specific activation receptor induces nk cell tolerance. | natural killer (nk) cell tolerance mechanisms are incompletely understood. one possibility is that they possess self-specific activation receptors that result in hyporesponsiveness unless modulated by self-major histocompatability complex (mhc)-specific inhibitory receptors. as putative self-specific activation receptors have not been well characterized, we studied a transgenic c57bl/6 mouse that ubiquitously expresses m157 (m157-tg), which is the murine cytomegalovirus (mcmv)-encoded ligand for ... | 2008 | 18606857 |
| tolerance of nk cells encountering their viral ligand during development. | during development, t and b cells encountering their cognate ligands via antigen-specific receptors are deleted or rendered anergic. like t and b cells, natural killer (nk) cells express certain receptors, such as ly49h, associated with immunoreceptor tyrosine-based activation motif-bearing adaptor proteins that transmit activating signals through syk family kinases. ly49h binds with high affinity to a mouse cytomegalovirus (mcmv)-encoded glycoprotein, m157, but does not recognize self-antigens. ... | 2008 | 18606858 |