Publications

cytomegalovirus mck-2 controls mobilization and recruitment of myeloid progenitor cells to facilitate dissemination.	murine cytomegalovirus encodes a secreted, pro-inflammatory chemokine-like protein, mck-2, that recruits leukocytes and facilitates viral dissemination. we have shown that mck-2-enhanced recruitment of myelomonocytic leukocytes with an immature phenotype occurs early during infection and is associated with efficient viral dissemination. expression of mck-2 drives the mobilization of a population of leukocytes from bone marrow that express myeloid marker mac-1 (cd11b), intermediate levels of gr-1 ...	2006	16046529
mouse embryonic stem cells are not susceptible to cytomegalovirus but acquire susceptibility during differentiation.	cytomegalovirus (cmv) is the most significant infectious cause of congenital anomalies of the central nervous system caused by intrauterine infection in humans. the timing of infection and the susceptibility of cells in early gestational stages are not well understood. in this study we investigated the susceptibility of embryonic stem (es) cells to cmv infection during differentiation.	2006	16470616
crystal structure of the murine cytomegalovirus mhc-i homolog m144.	large dna viruses of the herpesvirus family produce proteins that mimic host mhc-i molecules as part of their immunoevasive strategy. the m144 glycoprotein, expressed by murine cytomegalovirus, is thought to be an mhc-i homolog whose expression prolongs viral survival in vivo by preventing natural killer cell activation. to explore the structural basis of this m144 function, we have determined the three-dimensional structure of an m144/beta2-microglobulin (beta2m) complex at 1.9a resolution. thi ...	2006	16500675
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
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
mixed infection with multiple strains of murine cytomegalovirus occurs following simultaneous or sequential infection of immunocompetent mice.	as with human cytomegalovirus (hcmv) infection of humans, murine cmv (mcmv) infection is widespread in its natural host, the house mouse mus domesticus, and may consist of mixed infection with different cmv isolates. the incidence and mechanisms by which mixed infection occurs in free-living mice are unknown. this study used two approaches to determine whether mixed infection with mcmv could be established in laboratory mice. the first utilized two naturally occurring mcmv strains, n1 and g4, in ...	2006	16603512
role for tlr2 in nk cell-mediated control of murine cytomegalovirus in vivo.	natural killer (nk) cells are essential for the early control of murine cytomegalovirus (mcmv) infection. here, we demonstrate that toll-like receptor 2 (tlr2) plays a role in the nk cell-mediated control of mcmv. tlr2 knockout (ko) mice had elevated levels of mcmv in the spleen and liver on day 4 postinfection compared to c57bl/6 mice. in vivo depletion of nk cells with anti-nk1.1 antibodies, however, eliminated the differences in viral titers between the two groups, suggesting that the effect ...	2006	16611887
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
induction of apoptosis limits cytomegalovirus cross-species infection.	cross-species infections are responsible for the majority of emerging and re-emerging viral diseases. however, little is known about the mechanisms that restrict viruses to a certain host species, and the factors viruses need to cross the species barrier and replicate in a different host. cytomegaloviruses (cmvs) are representatives of the beta-herpesviruses that are highly species specific. they replicate only in cells of their own or a closely related species. in this study, the molecular mech ...	2006	16688216
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
cellular and molecular requirements for association of the murine cytomegalovirus protein m4/gp34 with major histocompatibility complex class i molecules.	the murine cytomegalovirus (mcmv) protein m4/gp34 is unique among known viral genes that target the major histocompatibility complex (mhc) class i pathway of antigen presentation in the following two ways: it is found in association with class i mhc molecules at the cell surface, and it inhibits antigen presentation without reducing cell surface class i levels. the current study was undertaken to define more clearly the structural and cellular requirements for m4/gp34 association with the mhc cl ...	2006	16731943
pathogenesis and vertical transmission of a transplacental rat cytomegalovirus.	cytomegalovirus (cmv) congenital infection is the major viral cause of well-documented birth defects in human. because cmv is species-specific, the main obstacle to developing animal models for congenital infection is the difference in placental architecture, which preludes virus transmission across the placenta. the rat placenta, resembling histologically to that of human, could therefore facilitate the study of cmv congenital infection in human.	2006	16737550
differential expression of the immediate-early 2 and 3 proteins in developing mouse brains infected with murine cytomegalovirus.	murine cytomegalovirus (mcmv) immediate-early (ie) 2 protein has been reported to be dispensable for growth and latency in mice. therefore, its role in viral pathogenesis and tissue tropism is not known. here we prepared specific antibodies to the ie2 and ie3 proteins by using fusion proteins expressed in escherichia coli as antigens. immunostaining of mcmv-infected cultured fibroblasts revealed ie2 protein to be expressed diffusely in the nucleoplasm similar to the ie1 protein. in contrast, exp ...	2006	16755372
genes of murine cytomegalovirus exist as a number of distinct genotypes.	murine cytomegaloviruses encode a number of genes which modulate polymorphic host immune responses. we suggest that these viral genes should themselves therefore exhibit sequence polymorphism. additionally, clinical isolates of human cytomegalovirus (hcmv) have been shown to vary extensively from the common laboratory strains. almost all research conducted on murine cytomegalovirus (mcmv) has used the laboratory strains smith and k181, which have been extensively passaged in vitro and in vivo si ...	2006	16781754
four distinct patterns of memory cd8 t cell responses to chronic murine cytomegalovirus infection.	cmvs are beta herpesviruses that establish lifelong latent infection of their hosts. acute infection of c57bl/6 mice with murine cmv elicits a very broad cd8 t cell response, comprising at least 24 epitopes from 18 viral proteins. in contrast, we show here that the cd8 t cell response in chronically infected mice was dominated by only five epitopes. altogether, four distinct cd8 t cell kinetic patterns were evident. responses to some epitopes, including m45, which dominates the acute response, c ...	2006	16785542
experimental confirmation of global murine cytomegalovirus open reading frames by transcriptional detection and partial characterization of newly described gene products.	murine cytomegalovirus (mcmv) and human cmv (hcmv) share many features making the mouse system a potential small-animal model for hcmv. although the genomic dna sequence and the predicted open reading frames (orfs) of mcmv have been determined, experimental evidence that the orfs are actually transcribed has been lacking. we developed an mcmv global-dna microarray that includes all previously predicted orfs and 14 potential ones. a total of 172 orfs were confirmed to be transcribed, including 7 ...	2006	16809293
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
cytomegalovirus encodes a positive regulator of antigen presentation.	murine cytomegalovirus encodes three regulators of antigen presentation to antiviral cd8 t cells. according to current paradigms, all three regulators are committed to the inhibition of the presentation of antigenic peptides. whereas m152/gp40 catalyzes the retention of peptide-loaded major histocompatibility complex (mhc) class i molecules in a cis-golgi compartment, m06/gp48 binds stably to class i molecules and directs them into the cellular cargo-sorting pathway of lysosomal degradation. reg ...	2006	16840340
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
rat cytomegalovirus infection interferes with anti-cd4 mab-(rib 5/2) mediated tolerance and induces chronic allograft damage.	in order to assess the role of heterologous immunity on tolerance induction (ti) by signal 1 modification, the influence of rat cytomegalovirus infection (rcmvi) on ti by a non-depleting monoclonal anti-cd4 mab (monoclonal antibody) (rib 5/2) in a rat kidney transplant (ktx) model was investigated. orthotopic rat ktx (dark agouty (da)-->lewis (lew)) was performed after ti with rib 5/2 [10 mg/kg body weight (bw); day -1, 0, 1, 2, 3; i.p. (intraperitoneal route)]. rcmvi (5x10e5 plaque forming unit ...	2006	16869800
beta-adrenoceptor blockade markedly attenuates transgene expression from cytomegalovirus promoters within the cardiovascular system.	the major immediate-early cytomegalovirus enhancer/promoter (miecmv), widely used in cardiovascular gene therapy, contains several positively regulatory camp response elements (cre). catecholamine signaling via beta-adrenoceptors might increase transgene expression from miecmv, and if so, beta-blockers may have a detrimental effect on the efficacy of clinical cardiovascular gene therapy strategies.	2006	16888240
acute rejection and cardiac allograft vascular disease is reduced by suppression of subclinical cytomegalovirus infection.	anticytomegalovirus (cmv) prophylaxis prevents the acute disease but its impact on subclinical infection and allograft outcome is unknown. we sought to determine whether cmv prophylaxis administered for three months after heart transplant would improve patient outcomes.	2006	16906040
ikaros is required for plasmacytoid dendritic cell differentiation.	plasmacytoid dendritic cells (pdcs) are specialized dcs that produce high levels of type i ifn upon viral infection. despite their key immunoregulatory role, little is known about pdc ontogeny or how developmental events regulate their function. we show that mice expressing low levels of the transcription factor ikaros (ik(l/l)) lack peripheral pdcs, but not other dc subsets. loss of pdcs is associated with an inability to produce type i ifn after challenge with toll-like receptor-7 and -9 ligan ...	2006	16912230
dap12 signaling regulates plasmacytoid dendritic cell homeostasis and down-modulates their function during viral infection.	dap12 is an itam-containing adaptor molecule conveying activating properties to surface receptors on many cell types. we show here that dap12 paradoxically down-modulates plasmacytoid dendritic cell (pdc) cytokine production in vivo during murine cmv (mcmv) infection. higher levels of ifn-alphabeta and il-12 were detected upon mcmv infection or cpg treatment in dap12-deficient (dap12(o)) mice as compared with wild-type (wt) mice. this resulted from altered homeostasis and enhanced responsiveness ...	2006	16920926
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
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
stat1 contributes to dsrna inhibition of liver regeneration after partial hepatectomy in mice.	increasing evidence suggests that liver regeneration is suppressed in patients with chronic hcv infection; however, the underlying mechanisms remain unclear. previously, we demonstrated that injection of the synthetic double-stranded rna (dsrna) poly i:c to mimic viral infection suppresses liver regeneration in the partial hepatectomy (phx) model, whereby ifn-gamma contributes to the inhibition. in this study, we examined the role of the ifn-gamma-activated downstream signal (stat1) and genes (i ...	2006	17006930
dap12 signaling directly augments proproliferative cytokine stimulation of nk cells during viral infections.	nk cells vigorously proliferate during viral infections. during the course of murine cmv infection, this response becomes dominated by the preferential proliferation of nk cells that express the activation receptor ly49h. the factors driving such selective nk cell proliferation have not been characterized. in this study, we demonstrate that preferential nk cell proliferation is dependent on dap12-mediated signaling following the binding of ly49h to its virally encoded ligand, m157. ly49h signali ...	2006	17015680
[inhibitory effect of murine cytomegalovirus infection on neural stem cells' differentiation and its mechanisms].	cytomegalovirus (cmv) is the leading infectious cause of congenital anomalies of the central nervous system caused by intrauterine infection. however, the exact pathogenesis of these brain abnormalities has not been fully elucidated. it has been reported that periependymitis, periventricular necrosis and calcification are the most frequent findings in the brains of congenital cmv infection. because a number of multipotential neural stem cells (nscs) have been identified from ventricular zone, it ...	2006	17044975
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
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
identification and characterization of two antisense transcripts from the major immediate early region of rat cytomegalovirus.	we have identified and characterized two antisense transcripts from the rat cytomegalovirus (rcmv) major immediate early (mie) region. these transcripts, designated ie-as1 and ie-as2, are complementary to part of the sense ie1 transcript. the ie-as transcripts were first detected in peripheral blood leukocytes (pbl) of rcmv-infected rats at 7 days post-infection (pi) in the absence of ie1 transcription. nevertheless, both the ie1 and ie-as transcripts were found at the same time in the salivary ...	2005	16052287
effect of posttranscriptional regulatory elements on transgene expression and virus production in the context of retrovirus vectors.	ineffective transgene expression in a sufficient amount of target cells is still a limitation in retroviral vector mediated gene therapy. thus, we systematically evaluated four genetic modulators, (i) the woodchuck posttranscriptional regulatory element (wpre), (ii) the mouse rna transport element (rte), (iii) the constitutive transport element (cte) of the simian retrovirus type 1 (srv-1), and (iv) the 5' untranslated region of the human heat shock protein 70 (hsp70 5'utr), all of them involved ...	2005	16054668
neuropathogenesis in cytomegalovirus infection: indication of the mechanisms using mouse models.	cytomegalovirus (cmv) is the most frequent infectious cause of developmental brain disorders and also causes brain damage in immunocompromised individuals. although the brain is one of the main targets of cmv infection, little is known about the neuropathogenesis of the brain disorders caused by cmv in humans because of the limitations in studying human subjects. murine cmv (mcmv) is similar to human cmv (hcmv) in terms of genome structure, pattern of gene expressions, cell tropism and infectiou ...	2005	16100703
functional analysis of granzyme m and its role in immunity to infection.	cytotoxic lymphocytes express a large family of granule serine proteases, including one member, granzyme (grz)m, with a unique protease activity, restricted expression, and distinct gene locus. although a number of grzs, including grzm, have been shown to mediate target cell apoptosis in the presence of perforin, the biological activity of grz has been restricted to control of a number of viral pathogens, including two natural mouse pathogens, ectromelia, and murine cmv (mcmv). in this article, ...	2005	16116214
identification of a monoclonal antibody from peromyscus maniculatus (deer mouse) cytomegalovirus (pcmv) which binds to a protein with homology to the human cmv matrix protein hcmv pp71.	in this study we identified and characterized a monoclonal antibody against the matrix protein of a cytomegalovirus isolated from the common deer mouse (peromyscus maniculatus) (pcmv). the monoclonal antibody was isolated using previously described technology which could be applied to the production of monoclonal antibodies against zoonotic disease. the antibody was found to react with a protein homologous to the human cytomegalovirus (hcmv) matrix protein (pp71), the product of the ul82 open re ...	2005	15582693
interaction between conventional dendritic cells and natural killer cells is integral to the activation of effective antiviral immunity.	dendritic cells (dcs) regulate various aspects of innate immunity, including natural killer (nk) cell function. here we define the mechanisms involved in dc-nk cell interactions during viral infection. nk cells were efficiently activated by murine cytomegalovirus (mcmv)-infected cd11b(+) dcs. nk cell cytotoxicity required interferon-alpha and interactions between the nkg2d activating receptor and nkg2d ligand, whereas the production of interferon-gamma by nk cells relied mainly on dc-derived int ...	2005	16142239
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
mitochondrial cell death suppressors carried by human and murine cytomegalovirus confer resistance to proteasome inhibitor-induced apoptosis.	human cytomegalovirus carries a mitochondria-localized inhibitor of apoptosis (vmia) that is conserved in primate cytomegaloviruses. we find that inactivating mutations within ul37x1, which encodes vmia, do not substantially affect replication in townevaratcc (towne-bac), a virus that carries a functional copy of the betaherpesvirus-conserved viral inhibitor of caspase 8 activation, the ul36 gene product. in towne-bac infection, vmia reduces susceptibility of infected cells to intrinsic death in ...	2005	16160147
rat cytomegalovirus and listeria monocytogenes infection enhance chronic rejection after allogenic rat lung transplantation.	the role of infection in the pathomechanism of obliterative bronchiolitis (ob) after human lung transplantation is controversial. in a rat lung transplantation model, we analyzed the effect of viral [rat cytomegalovirus (rcmv)] and bacterial infection [listeria monocytogenes (lm)] on the development of chronic allograft rejection. fisher rats underwent single left lung transplantation with allografts from lewis rats. postoperatively, animals were infected with either rcmv or lm, or served as non ...	2005	16162104
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
expression of il-1beta and tnf-alpha in mcmv myocarditis and its role.	in order to study the expression of il-1beta and tnf-alpha in the myocardium of mcmv myocarditis and their role in the myocardial damages, 60 balb/c mice of 4 weeks were randomly divided into two groups: 36 were injected intraperitoneally with mcmv and 24 served as control group. immunohistochemistry was used to detect il-1beta and tnf-alpha expression in the myocardium, and myocardial lesions were observed histopathologically. histopathological study on the myocardium from infected mice reveale ...	2005	16201263
viral interference with antigen presentation to cd8+ t cells: lessons from cytomegalovirus.	cytomegaloviruses (cmv), in common with other herpesviruses, establish lifelong persistence in their hosts. these highly host-specific viruses each encode viral genes that interfere with antigen presentation to cd8+ t cells, although the molecular mechanisms by which this end is achieved differ for human and murine cmvs. in each case, there has been a presumption that these genes are necessary for virus persistence in the host. however, recent data in the murine model casts doubt on that presump ...	2005	16212522
myd88-dependent and -independent murine cytomegalovirus sensing for ifn-alpha release and initiation of immune responses in vivo.	antiviral immunity requires early and late mechanisms in which ifn-alpha and il-12 play major roles. however, the initial events leading to their production remain largely unclear. given the crucial role of tlr in innate recognition, we investigated their role in antiviral immunity in vivo. upon murine cmv (mcmv) infection, both myd88-/- and tlr9-/- mice were more susceptible and presented increased viral loads compared with c57bl/6, tlr2-/-, tlr3-/-, or tlr4-/- mice. however, in terms of resist ...	2005	16272328
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
rat cytomegalovirus induces a temporal downregulation of major histocompatibility complex class i cell surface expression.	herpesviruses are known to influence expression of major histocompatibility complex (mhc) class i molecules on the surface of infected cells using a variety of mechanisms. downregulation of mhc class i expression prohibits detection and elimination of infected cells by cytotoxic t lymphocytes. to investigate the effect of rat cytomegalovirus (rcmv) infection on mhc class i expression, we infected immortalized and primary rat fibroblasts with rcmv and monitored surface expression of mhc class i m ...	2005	16359227
genetic analysis of innate resistance to mouse cytomegalovirus (mcmv).	innate immunity is inherited and is, therefore, particularly susceptible to analysis by classical genetic methods. the 'phenotype first' approach has already revealed the principal receptors of the innate immune system as well as several essential signalling intermediates. it has recently emerged that innate resistance to mouse cytomegalovirus (mcmv) infection depends upon a large number of host genes with non-redundant functions; hence, random germline mutagenesis frequently causes susceptibili ...	2005	16420746
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
systemic priming-boosting immunization with a trivalent plasmid dna and inactivated murine cytomegalovirus (mcmv) vaccine provides long-term protection against viral replication following systemic or mucosal mcmv challenge.	we previously demonstrated that vaccination of balb/c mice with a pool of 13 plasmid dnas (pdnas) expressing murine cytomegalovirus (mcmv) genes followed by formalin-inactivated mcmv (fi-mcmv) resulted in complete protection against viral replication in the spleen and salivary glands following sublethal intraperitoneal (i.p.) challenge. here, we found that following intranasal (i.n.) challenge, titers of virus in the lungs of the immunized mice were reduced approximately 1,000-fold relative to t ...	2005	15596812
mouse cytomegalovirus early m112/113 proteins control the repressive effect of ie3 on the major immediate-early promoter.	the mouse cytomegalovirus major immediate-early (ie) transcript is differentially spliced to produce two ie proteins: ie1, which functions partly to maintain its own promoter, the major ie promoter (miep), free from repression, and ie3, which functions partly as a repressor of miep. paradoxically, the site where transcription of the viral genome occurs is also the site where the greatest amounts of ie3 accumulate. this raises the question of how the repression capabilities of ie3 are controlled ...	2005	15596821
role for tumor necrosis factor alpha in murine cytomegalovirus transcriptional reactivation in latently infected lungs.	interstitial pneumonia is a major clinical manifestation of primary or recurrent cytomegalovirus (cmv) infection in immunocompromised recipients of a bone marrow transplant. in a murine model, lungs were identified as a prominent site of cmv latency and recurrence. pulmonary latency of murine cmv is characterized by high viral genome burden and a low incidence of variegated immediate-early (ie) gene expression, reflecting a sporadic activity of the major ie promoters (mieps) and enhancer. the en ...	2005	15596827
conditional cytomegalovirus replication in vitro and in vivo.	we have established a conditional gene expression system for cytomegalovirus which allows regulation of genes independently from the viral replication program. due to the combination of all elements required for regulated expression in the same viral genome, conditional viruses can be studied in different cell lines in vitro and in the natural host in vivo. the combination of a self-sufficient tetracycline-regulated expression cassette and flp recombinase-mediated insertion into the viral genome ...	2005	15596841
natural killer cells utilize both perforin and gamma interferon to regulate murine cytomegalovirus infection in the spleen and liver.	natural killer (nk) cells are critical for innate regulation of the acute phase of murine cytomegalovirus (mcmv) infection and have been reported to utilize perforin (pfp)- and gamma interferon (ifn-gamma)-dependent effector mechanisms in an organ-specific manner to regulate mcmv infection in the spleen and liver. in this study, we further examined the roles of nk cells, pfp, and ifn-gamma in innate immunity to mcmv infection. with the recently described nk cell-deficient (nkd) mouse, we confirm ...	2005	15596864
genetic dissection of innate immunity to infection: the mouse cytomegalovirus model.	resistance to infection is largely inherited rather than acquired, and is encoded by a definable set of host genes designated the 'resistome'. logically speaking, piecemeal disruption of the resistome gives us the best chance to define it, and the most spectacular advances in understanding innate immunity have grown from spontaneous or induced germline mutations of the resistome. mutations induced by random germline mutagenesis have now become so numerous that we are nearly in a position to defi ...	2005	15653308
the english strain of rat cytomegalovirus (cmv) contains a novel captured cd200 (vox2) gene and a spliced cc chemokine upstream from the major immediate-early region: further evidence for a separate evolutionary lineage from that of rat cmv maastricht.	sequence data for eight genes, together with time-course northern blotting and 3'- and 5'-race (rapid amplification of cdna ends) analysis for some mrnas from a 12 kb region upstream from the major immediate-early (mie) genes of the english isolate of rat cytomegalovirus (rcmv), are presented. the results identified important differences compared to both murine cytomegalovirus (mcmv) and the maastricht isolate of rcmv. a striking finding is the presence of a highly conserved, rightwards-oriented ...	2005	15659745
monocyte chemoattractant protein-1 and ccr2 interactions are required for ifn-alpha/beta-induced inflammatory responses and antiviral defense in liver.	ifn-alpha/beta-mediated functions promote production of mip-1alpha (or ccl3) by mediating the recruitment of mip-1alpha-producing macrophages to the liver during early infection with murine cmv. these responses are essential for induction of nk cell inflammation and ifn-gamma delivery to support effective control of local infection. nevertheless, it remains to be established if additional chemokine functions are regulated by ifn-alpha/beta and/or play intermediary roles in supporting macrophage ...	2005	15661915
leukotriene b4 protects latently infected mice against murine cytomegalovirus reactivation following allogeneic transplantation.	human cmv is often associated with transplant rejection and opportunistic infections such as pneumonia in immunosuppressed patients. current anti-cmv therapies, although effective, show relatively high toxicity, which seriously limits their long-term use. in this study, we provide evidence that leukotriene b(4) (ltb(4)) plays an important role in the fight against murine cmv (mcmv) infection in vivo. intravenous administration of 50 and 500 ng/kg/day of ltb(4) to mice infected with a lethal dose ...	2005	15661920
selective down-regulation of the nkg2d ligand h60 by mouse cytomegalovirus m155 glycoprotein.	both human and mouse cytomegaloviruses (cmvs) encode proteins that inhibit the activation of nk cells by down-regulating cellular ligands for the activating nk cell receptor nkg2d. up to now, three ligands for the nkg2d receptor, named rae-1, h60, and mult-1, have been identified in mice. the resistance of mouse strains to murine cmv (mcmv) infection is determined by their ability to generate an effective nk cell response. the mcmv gene m152, a member of the m145 gene family, down-regulates the ...	2005	15709011
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
direct effects of t-bet and mhc class i expression, but not stat1, on peripheral nk cell maturation.	the homeostatic maturation of nk cells is severely impaired in mice lacking the transcription factor t-bet, and the expression of the nk cell maturation marker killer cell lectin-like receptor g1 (klrg1) has been shown to be dependent on mhc class i molecules. interferon (ifn)-gamma signaling via the signal transducer and activator of transcription (stat)1 is vital for t-bet and mhc class i induction. here we investigated the relationship between stat1, t-bet, and mhc class i molecules with rega ...	2005	15719366
nasal peptide vaccination elicits cd8 responses and reduces viral burden after challenge with virulent murine cytomegalovirus.	infection of balb/c mice with murine cytomegalovirus (mcmv) leads to cd8 cell responses to an immunodominant epitope yphfmptnl. we presented this epitope as a nasal peptide vaccine in combination with cholera toxin adjuvant, and evaluated immune responses and protection from mcmv challenge. vaccination of naive mice generated elevated numbers of peptide-specific interferon-gamma-secreting splenocytes (median 80/million, range 60 to 490), compared to control mice (median 2/million, range -4.5 to ...	2005	15722596
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
cd13/aminopeptidase n and murine cytomegalovirus infection.	cd13/aminopeptidase n is a membrane-bound metalloproteinase implicated in human cytomegalovirus (hcmv) infection and pathogenesis. anti-cd13 antibodies can neutralize hcmv infectivity, and hcmv viremia after bone marrow transplantation induces anti-cd13 autoantibodies which correlate with development of chronic graft vs. host disease. we examined whether murine cd13/apn was similarly implicated in murine cytomegalovirus (mcmv) disease. mcmv infection did induce anti-cd13 antibodies in mice in a ...	2005	15749117
evolution of diverse antiviral cd8+ t cell populations after murine cytomegalovirus infection.	cytomegalovirus (cmv) is a major human pathogen normally controlled by cellular immune responses. the infection can be modeled in the mouse using murine cmv (mcmv). during the latent phase of infection, two different patterns of cd8(+) t cell responses have been observed: some specificities show increasing frequencies over time ("memory inflation"), while others, which are present acutely, are barely detectable at later time points. this distinction is independent of initial immunodominance. we ...	2005	15756645
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
immune modulation of the hypothalamic-pituitary-adrenal (hpa) axis during viral infection.	compelling data has been amassed indicating that soluble factors, or cytokines, emanating from the immune system can have profound effects on the neuroendocrine system, in particular the hypothalamic- pituitary-adrenal (hpa) axis. hpa activation by cytokines (via the release of glucocorticoids), in turn, has been found to play a critical role in restraining and shaping immune responses. thus, cytokine-hpa interactions represent a fundamental consideration regarding the maintenance of homeostasis ...	2005	15802953
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
highly protective in vivo function of cytomegalovirus ie1 epitope-specific memory cd8 t cells purified by t-cell receptor-based cell sorting.	reconstitution of antiviral cd8 t cells is essential for controlling cytomegalovirus (cmv) infection after bone marrow transplantation. accordingly, polyclonal cd8 t cells derived from balb/c mice infected with murine cmv protect immunocompromised adoptive transfer recipients against cmv disease. the protective population comprises cd8 t cells with t-cell receptors (tcrs) specific for defined and for as-yet-unknown viral epitopes, as well as a majority of nonprotective cells with unrelated speci ...	2005	15827154
evaluation of promoters for foreign gene expression in the e3 region of bovine adenovirus type-3.	in order to optimize foreign gene expression in the e3 region of badv-3, we constructed full-length badv-3 genomic dna clones containing a reporter gene (truncated glycoprotein gd of bovine herpesvirus 1, gdt), under the control of exogenous promoters inserted in either direction in the e3 region. irrespective of exogenous transcriptional elements, viable recombinant badv-3 viruses could only be isolated when the gdt expression cassettes were inserted in the e3 region parallel to the direction o ...	2005	15845268
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
rapid emergence of escape mutants following infection with murine cytomegalovirus in immunodeficient mice.	natural killer (nk) cells play a crucial role in the initial host defense against pathogens such as murine cytomegalovirus (mcmv). they respond rapidly and effectively control pathogen replication while the adaptive immune system is being activated. however, in the absence of an adaptive immune system, an effective initial nk cell response is not sufficient for long-term pathogen control as demonstrated by the late recrudescence of disease and mortality in immunodeficient mice infected with mcmv ...	2005	15870022
a cytomegaloviral protein reveals a dual role for stat2 in ifn-{gamma} signaling and antiviral responses.	a mouse cytomegalovirus (mcmv) gene conferring interferon (ifn) resistance was identified. this gene, m27, encodes a 79-kd protein that selectively binds and down-regulates for signal transducer and activator of transcription (stat)-2, but it has no effect on stat1 activation and signaling. the absence of pm27 conferred mcmv susceptibility to type i ifns (alpha/beta), but it had a much more dramatic effect on type ii ifns (gamma) in vitro and in vivo. a comparative analysis of m27(+) and m27(-) ...	2005	15883169
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
a lymphotoxin-ifn-beta axis essential for lymphocyte survival revealed during cytomegalovirus infection.	the importance of lymphotoxin (lt) betar (ltbetar) as a regulator of lymphoid organogenesis is well established, but its role in host defense has yet to be fully defined. in this study, we report that mice deficient in ltbetar signaling were highly susceptible to infection with murine cmv (mcmv) and early during infection exhibited a catastrophic loss of t and b lymphocytes, although the majority of lymphocytes were themselves not directly infected. moreover, bone marrow chimeras revealed that l ...	2005	15905567
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
predicting coding potential from genome sequence: application to betaherpesviruses infecting rats and mice.	prediction of protein-coding regions and other features of primary dna sequence have greatly contributed to experimental biology. significant challenges remain in genome annotation methods, including the identification of small or overlapping genes and the assessment of mrna splicing or unconventional translation signals in expression. we have employed a combined analysis of compositional biases and conservation together with frame-specific g+c representation to reevaluate and annotate the genom ...	2005	15919911
antiviral synergism.		2005	15920514
[balb/c mice model system of cytomegalovirus-induced myocarditis].	to establish a balb/c mice model system of cytomegalovirus-induced myocarditis.	2005	15932673
the host type i interferon response to viral and bacterial infections.	type i interferons (ifn) are well studied cytokines with anti-viral and immune-modulating functions. type i ifns are produced following viral infections, but until recently, the mechanisms of viral recognition leading to ifn production were largely unknown. toll like receptors (tlrs) have emerged as key transducers of type i ifn during viral infections by recognizing various viral components. furthermore, much progress has been made in defining the signaling pathways downstream of tlrs for type ...	2005	15987599
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
phospholipase c-gamma 2 is a critical signaling mediator for murine nk cell activating receptors.	phospholipase c-gamma (plcgamma) is a key regulator of intracellular ca(2+) mobilization. two isoforms of plcgamma have been identified, plcgamma1 and plcgamma2. previously, in vitro studies indicated that activating nk cell receptors signal through both isoforms. however, plcgamma2 deficiency alone was sufficient to induce a substantial impairment of nk cell-mediated cytotoxicity in vitro. why plcgamma2 is more important than plcgamma1 for nk cell activation and whether plcgamma2 is also critic ...	2005	16002670
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
murine cytomegalovirus resistant to antivirals has genetic correlates with human cytomegalovirus.	human cytomegalovirus (hcmv) resistance to antivirals is a significant clinical problem. murine cytomegalovirus (mcmv) infection of mice is a well-described animal model for in vivo studies of cmv pathogenesis, although the mechanisms of mcmv antiviral susceptibility need elucidation. mutants resistant to nucleoside analogues aciclovir, adefovir, cidofovir, ganciclovir, penciclovir and valaciclovir, and the pyrophosphate analogue foscarnet were generated by in vitro passage of mcmv (smith) in in ...	2005	16033961
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
t cell-mediated restriction of intracerebral murine cytomegalovirus infection displays dependence upon perforin but not interferon-gamma.	the authors have previously reported that adoptive transfer of splenocytes suppresses murine cytomegalovirus (mcmv) brain infection following intracerebroventricular injection of immunodeficient mice and that depletion of thy 1.2+ t lymphocytes abolishes this suppressive effect. here the authors report that splenocytes depleted of cd4+ t lymphocytes prior to adoptive transfer retained their ability to control viral expression in the brain. in sharp contrast, depletion of the cd8+ t-cell populati ...	2005	16036807
systemic immune deficiency necessary for cytomegalovirus invasion of the mature brain.	cytomegalovirus (cmv) is a significant opportunistic pathogen associated with aids and immunosuppressive therapy. infection of the mature central nervous system (cns) can cause significant pathology with associated neurological deficits, mental disorders, and cognitive impairment and may have potentially fatal consequences. using genetically immunocompromised mice, we studied mechanisms of cmv invasion into, and behavior within, the cns. adult immunodeficient (nude and scid) and control mice wer ...	2004	14722303
recognition of infected cells by natural killer cells.	under the influence of cytokines associated with innate immunity, natural killer (nk) cells rapidly become activated and migrate to sites of infection. upon contact with infected parenchyma they proliferate, release cytokines and/or kill cells harboring pathogens. multiple stimulatory and inhibitory receptors can provide the integrated signals that trigger this contact-mediated nk-cell function. recent work has begun to define the ligands for these receptors in the context of infection by certai ...	2004	14734107