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the rgd sequence in the cytomegalovirus dna polymerase accessory protein can mediate cell adhesion.the murine cytomegalovirus (mcmv) polymerase processivity factor ppm44 (also referred to as pp50) is an abundant phosphoprotein found in mcmv-infected cells. sequence analysis of the mcmv m44 open reading frame revealed an "rgd" motif that is also present in the human cytomegalovirus (hcmv) ul44 open reading frame. in this report, histidine-tagged m44 protein produced in escherichia coli or the vaccinia/t7 expression system was purified to near homogeneity by metal chelation affinity chromatogra ...200010873773
murine cytomegalovirus infection causes apoptosis of uninfected retinal cells.to determine the role of apoptosis in prevention and/or exacerbation of retinal disease in a mouse model of cytomegalovirus retinitis.200010892869
the immunogenicity of human and murine cytomegaloviruses.cytomegaloviruses are strictly host-species-specific. during an aeon of co-evolution, virus and host have found an arrangement: the productive and cytopathogenic cycle of viral gene expression is held in check by the host's immune response. as a consequence, cytomegalovirus disease is restricted to the immunocompromised host. the virus has evolved strategies to avoid its elimination and eventually hides itself in a silent state, referred to as 'viral latency'. redundant molecular mechanisms have ...200010899017
construction and characterization of murine cytomegaloviruses that contain transposon insertions at open reading frames m09 and m83.a transposon derived from escherichia coli tn3 was introduced into the genome of murine cytomegalovirus (mcmv) to generate a pool of viral mutants, including two recombinant viruses that contained the transposon sequence within open reading frames m09 and m83. our studies provide the first direct evidence to suggest that m09 is not essential for viral replication in mouse nih 3t3 cells. studies in cultured cells and in both balb/c-byj and cb17 severe combined immunodeficient (scid) mice indicate ...200010906194
complete dna sequence of the rat cytomegalovirus genome.we have determined the complete genome sequence of the maastricht strain of rat cytomegalovirus (rcmv). the rcmv genome has a length of 229,896 bp and is arranged as a single unique sequence flanked by 504-bp terminal direct repeats. rcmv was found to have counterparts of all but one of the open reading frames (orfs) that are conserved between murine cmv (mcmv) and human cmv (hcmv). like hcmv, rcmv lacks homologs of the genes belonging to the mcmv m02 glycoprotein gene family. however, rcmv cont ...200010906222
suppression of collagen induced arthritis in mice utilizing plasmid dna encoding interleukin 10.to investigate the therapeutic efficacy as well as the immunological effects of inoculation of an expression vector encoding interleukin 10 (il-10) in murine type ii collagen induced arthritis (cia).200010914840
immune transfer protects severely immunosuppressed mice from murine cytomegalovirus retinitis and reduces the viral load in ocular tissue.cytomegalovirus (cmv) retinitis is a sight-threatening disease that affects immunosuppressed people and is prevalent in people with aids. the purpose of this study was to evaluate murine cmv (mcmv) retinitis in a replenishing model with adoptive immune transfer into severely immunosuppressed animals. adult balb/c mice, immunosuppressed with cyclophosphamide, were infected subretinally with 5x102 plaque-forming units of mcmv. four to six hours later, 3-4x107 donor cells were transferred by intrav ...200010950756
the thymidylate synthase inhibitor zd1694 potently inhibits murine and human cytomegalovirus replication in quiescent fibroblasts.tomudex (zd1694) is a quinazoline-based folate analog and a powerful inhibitor of cellular thymidylate synthase and is approved in europe for use in oncology. here the first evidence of its activity against murine and human cytomegalovirus (mcmv and hcmv) is reported. zd1694 irreversibly inhibited the replication and dna synthesis of both viruses in quiescent fibroblasts. the corresponding 50% effective concentrations were 0.006 and 0.002 microm respectively, whereas the 50% cytotoxic concentrat ...200010996399
enhanced green fluorescent protein as a marker for localizing murine cytomegalovirus in acute and latent infection.a recombinant murine cytomegalovirus (mcmv) that expresses enhanced green fluorescent protein (egfp) under control of the native immediate-early 1/3 promoter was constructed to detect directly sites of viral activity in latent and reactivated infections. the recombinant virus had acute and latent infection characteristics similar to those of wild-type mcmv. rare green-fluorescing foci were observed in paraffin sections from lungs and spleens infected latently. positive immunoperoxidase staining ...200010996640
in vitro and in vivo characterization of a murine cytomegalovirus with a transposon insertional mutation at open reading frame m43.we have recently generated a pool of murine cytomegalovirus (mcmv) mutants by using a tn3-based transposon mutagenesis approach. in this study, one of the mcmv mutants, rvm43, which contained the transposon inserted in open reading frame m43, was characterized. our results provide the first direct evidence to suggest that m43 is not essential for viral replication in vitro in nih 3t3 cells. moreover, rvm43 exhibited a titer similar to that of the wild-type virus in the lungs, livers, spleens, an ...200011000218
replication-defective mutants of mouse cytomegalovirus protect against wild-type virus challenge.five temperature-sensitive mutants (tsm9, tsm13, tsm20, tsm22, tsm30) of murine cytomegalovirus have been shown previously not to produce infectious virus in mice. in the present study, the stage at which these mutants are blocked in their replication in vitro was examined by transcriptional analysis of 4 temporally regulated marker genes (ie-1, e-1, gb and gh) using a semi-quantitative reverse transcription polymerase chain reaction (rt-pcr) coupled with an electron microscopic analysis of infe ...200011002240
cytomegalovirus infection of the central nervous system stem cells from mouse embryo: a model for developmental brain disorders induced by cytomegalovirus.cytomegalovirus (cmv) is the most frequent infectious cause of developmental disorders of the central nervous system (cns) in humans. infection of the cns stem cells seems to be primarily responsible for the generation of the brain abnormalities. in this study, we evaluated the infectivity of murine cmv (mcmv) in epidermal growth factor (egf)-responsive cns stem cells prepared from fetal mouse brains, and studied the effect of infection on growth and differentiation of the stem cells. the cns st ...200011005206
characterization of cd4- cd8- cd3+ t-cell receptor-alphabeta+ t cells in murine cytomegalovirus infection.in this study, we have investigated that after the intraperitoneal infection with murine cytomegalovirus (mcmv), the cd3+ cd4- cd8-(double negative; dn) t-cell receptor (tcr)alphabeta+ t cells increased in peritoneal cavity, liver and spleen in both resistant c57bl/6 and susceptible balb/c mice. the total cellular population of these cells showed peak levels around day 5 after infection in all the three investigated organs and the following phenotypical and functional characteristics emerged. th ...200011012749
multifactorial protective mechanisms to limit viral replication in the lung of mice during primary murine cytomegalovirus infection.in this article, we investigated the protective host immune mechanisms against acute murine cytomegalovirus (mcmv) infection. for this purpose, we used various knockout mice lacking molecules, which include interferon-gamma (ifn-gamma), interferon-gamma receptor (ifn-gamma-r), interferon regulatory factor-1 (irf-1), inducible nitric oxide synthase (inos), and perforin. we also used mutant mice lacking fas molecule. when we infected these mice with mcmv and determined the viral titers in their lu ...200011016594
comparison between human cytomegalovirus pul97 and murine cytomegalovirus (mcmv) pm97 expressed by mcmv and vaccinia virus: pm97 does not confer ganciclovir sensitivity.the ul97 protein (pul97) of human cytomegalovirus (hcmv) is a protein kinase that also phosphorylates ganciclovir (gcv), but its biological function is not yet clear. the m97 protein (pm97) of mouse cytomegalovirus (mcmv) is the homolog of pul97. first, we studied the consequences of genetic replacement of m97 by ul97. using the infectious bacterial plasmid clone of the full-length mcmv genome (m. wagner, s. jonjic, u. h. koszinowski, and m. messerle, j. virol. 73:7056-7060, 1999), we replaced t ...200011044117
cutting edge: selective il-18 requirements for induction of compartmental ifn-gamma responses during viral infection.optimal protective effects for defense against infection require orchestration of immune responses spanning multiple host compartments and divergent local regulation at particular sites. during murine cytomegalovirus infections known to target spleen and liver, il-12-induced ifn-gamma from nk cells is crucial for resistance. however, the roles for il-18 and/or il-12 in regulating hepatic ifn-gamma responses, as compared with systemic or splenic responses, have not been defined. in this report, m ...200011046000
murine cytomegalovirus containing a mutation at open reading frame m37 is severely attenuated in growth and virulence in vivo.a pool of murine cytomegalovirus (mcmv) mutants was generated by using a tn3-based transposon mutagenesis procedure. one of the mutants, rvm37, which contained the transposon sequence at open reading frame m37, was characterized both in tissue culture and in immunocompetent balb/c and immunodeficient scid mice. our results provide the first direct evidence to suggest that m37 is not essential for viral replication in vitro in nih 3t3 cells. compared to the wild-type strain and a rescued virus th ...200011070005
the major immediate-early gene ie3 of mouse cytomegalovirus is essential for viral growth.the significance of the major immediate-early gene ie3 of mouse cytomegalovirus (mcmv) and that of the corresponding ie2 gene of human cytomegalovirus to viral replication are not known. to investigate the function of the mcmv ie3 regulatory protein, we generated two different mcmv recombinants that contained a large deletion in the ie3 open reading frame (orf). the mutant genomes were constructed by the bacterial artificial chromosome mutagenesis technique, and mcmv ie3 deletion mutants were re ...200011070009
identification of a k(d)-restricted antigenic peptide encoded by murine cytomegalovirus early gene m84.the two sister cytomegaloviruses (cmvs), human and murine cmv, have both evolved immune evasion functions that interfere with the major histocompatibility complex class i (mhc-i) pathway of antigen processing and presentation and are effectual in the early (e) phase of virus gene expression. however, studies on murine cmv have shown that e-phase immune evasion is leaky. an e-phase protein involved in immune evasion, namely m04-gp34, was found to simultaneously account for an antigenic peptide pr ...200011086134
potential pathways for regulation of nk and t cell responses: differential x-linked lymphoproliferative syndrome gene product sap interactions with slam and 2b4.sap, the gene that is altered or absent in the x-linked lymphoproliferative syndrome (xlp), encodes a small protein that comprises a single sh2 domain and binds to the cell-surface protein slam which is present on activated or memory t and b cells. because defective nk cell activity also has been reported in xlp patients, we studied the sap gene in nk cells. sap was induced upon viral infection of scid mice and shown to be expressed in nk cells by in vitro culturing in the presence of il-2. more ...200011099315
atherosclerosis in apoe knockout mice infected with multiple pathogens.cytomegalovirus (cmv) and chlamydia pneumoniae (cp) possibly contribute to atherosclerosis. murine cmv (mcmv) and cp increase lesion size in apoe knockout mice. in this study, apoe knockout mice were infected with mcmv and cp to determine whether infection with multiple pathogens increases lesion size to a greater extent than either pathogen alone and whether infection with mcmv changes serum cytokine levels in a manner that could increase lesion development. one group of mice received mcmv at 2 ...200111120928
identification and characterization of a spliced c-type lectin-like gene encoded by rat cytomegalovirus.the english isolate of rat cytomegalovirus (rcmv) encodes a 20-kda protein with a c-type lectin-like domain that is expressed in the delayed-early and late phases of the viral replication cycle. genomic sequence analysis of the restriction fragment kpnr of rcmv revealed significant homology to several c-type lectin-containing molecules implicated in natural killer (nk) and t-cell interactions, as well as genes from four poxviruses and african swine fever virus. the gene is spliced into five exon ...200111134273
nk1.1+ cells and murine cytomegalovirus infection: what happens in situ?nk cells mediate early host defense against viral infection. in murine cmv (mcmv) infection nk cells play a critical role in controlling viral replication in target organs, such as spleen and liver. until now it has not been possible to directly examine the role of nk cells in mcmv-induced inflammation in situ due to the inability to stain specifically for nk cells in infected tissues. in this study, we describe a method of in vivo fixation, resulting in the first identification of nk cells in s ...200111160226
murine cytomegalovirus open reading frame m27 plays an important role in growth and virulence in mice.using a tn3-based transposon mutagenesis approach, we have generated a pool of murine cytomegalovirus (mcmv) mutants. in this study, one of the mutants, rvm27, which contained the transposon sequence at open reading frame m27, was characterized both in tissue culture and in immunocompetent balb/c mice and immunodeficient scid mice. our results suggest that the m27 carboxyl-terminal sequence is dispensable for viral replication in vitro. compared to the wild-type strain and a rescued virus that r ...200111160668
non-specific antiviral activity of antisense molecules targeted to the e1 region of human papillomavirus.antisense phosphorothioate oligonucleotides (odn1 0x5 ome) directed against the e1 start region of human papillomavirus 11 (hpv11) can inhibit papillomavirus induced growth of implanted human foreskin in a mouse xenograft model. administration of a mismatch control oligonucleotide (odn9 0x5 ome), in which guanine was replaced with adenine in the same model, had no effect on papilloma induced growth. however, the apparent antiviral activity of odn1 0x5 ome was also shown in a lethal mouse cytomeg ...200011164505
isolation and analysis of an aciclovir-resistant murine cytomegalovirus mutant.an aciclovir (acv)-resistant murine cytomegalovirus (mcmv) was isolated from the smith strain and the mutant was analysed. attempts were also made to identify directly the mutated gene. the 50% inhibitory concentration (ic(50)) of acv for the mutant strain was approximately 30 times higher than that for the wild-type strain. the mutant strain was equally sensitive to ganciclovir (gcv), but slightly resistant to cidofovir (cdv) and foscarnet (pfa) when compared with the wild-type. molecular analy ...200111166858
characterization of virus-induced interferon-gamma responses in mice previously infected with murine cytomegalovirus.these studies demonstrate that in vitro stimulation of spleen cells from murine cytomegalovirus (mcmv) immune mice with mcmv-infected fibroblasts induces production of interferon (ifn)-gamma. this response is specific to mcmv, is not generalized to heterologous viruses, and also is not h-2 restricted. both early and late cmv antigens induce ifn-gamma. in in vitro cell depletion and direct cell selection experiments, t lymphocytes were responsible for ifn-gamma production. although both cd4 and c ...200111181145
immune responses and cytokine induction in the development of severe hepatitis during acute infections with murine cytomegalovirus.salivary gland-derived murine cytomegalovirus (sgv) infections of mice have been widely used as models of human cytomegalovirus infections and in the study of cmv biology. still, many aspects of sgv pathogenesis are not clearly defined. fatal and non-fatal sgv infections were investigated to characterize pathogenetic correlates of mortality and to assess the role of the immune response in disease progression. suppression of immune responses was observed in both lethal and sublethal infections. d ...200011205107
role of nitric oxide synthase type 2 in acute infection with murine cytomegalovirus.whether or not no plays a critical role in murine cmv (mcmv) infection has yet to be elucidated. in this study, we examined the role of no in acute infection with mcmv using no synthase type 2 (nos2)-deficient mice. nos2(-/-) mice were more susceptible to lethal infection with mcmv than nos2(+/+) mice and generated a much higher peak virus titer in the salivary gland after acute infection. a moderate increase in the mcmv titer was also observed in other organs of nos2(-/-) mice such as the splee ...200111207313
a ribonucleotide reductase homolog of cytomegalovirus and endothelial cell tropism.human cytomegalovirus infects vascular tissues and has been associated with atherogenesis and coronary restenosis. although established laboratory strains of human cytomegalovirus have lost the ability to grow on vascular endothelial cells, laboratory strains of murine cytomegalovirus retain this ability. with the use of a forward-genetic procedure involving random transposon mutagenesis and rapid phenotypic screening, we identified a murine cytomegalovirus gene governing endothelial cell tropis ...200111209080
the prevalence of viral antibodies during a large population fluctuation of house mice in australia.we studied the seroprevalence of three viruses (mouse cytomegalovirus (mcmv), minute virus of mice (mvm), and mouse parvovirus (mpv)) in house mice (mus domesticus) in 1995 7. in the first year average mouse density was less than 1 mouse/ha. from november 1995 to may 1996 the population increased at an average rate of 7% per week, a doubling time of about 10 weeks. from august 1996 to may 1997 the population increased at an average rate of 10% per week, a doubling time of about 7.5 weeks. from a ...200011218223
random, asynchronous, and asymmetric transcriptional activity of enhancer-flanking major immediate-early genes ie1/3 and ie2 during murine cytomegalovirus latency in the lungs.the lungs are a major organ site of cytomegalovirus (cmv) pathogenesis, latency, and recurrence. previous work on murine cmv latency has documented a high load and an even distribution of viral genomes in the lungs after the resolution of productive infection. initiation of the productive cycle requires expression of the ie1/3 transcription unit, which is driven by the immediate-early (ie) promoter p(1/3) and generates ie1 and ie3 transcripts by differential splicing. latency is molecularly defi ...200111222693
structural organization and analysis of the viral terminase gene locus of tupaia herpesvirus.tupaia herpesvirus (thv) was isolated from spontaneously degenerating tissue cultures of malignant lymphoma, lung, and spleen cell cultures of tree shrews (tupaia spp.). in order to determine the phylogenetic relatedness of thv the complete nucleotide sequence of the viral terminase (vter) gene locus (6223 bp) of tupaia herpesvirus strain 2 (thv-2) was elucidated and analysed. the vter gene locus, encoding one of the most highly conserved herpes viral proteins is composed of two exons. the intro ...200111226571
murine cytomegalovirus m78 protein, a g protein-coupled receptor homologue, is a constituent of the virion and facilitates accumulation of immediate-early viral mrna.the m78 protein of murine cytomegalovirus exhibits sequence features of a g protein-coupled receptor. it is synthesized with early kinetics, it becomes partially colocalized with golgi markers, and it is incorporated into viral particles. we have constructed a viral substitution mutant, smsubm78, which lacks most of the m78 orf. the mutant produces a reduced yield in cultured 10.1 fibroblast and ic21 macrophage cell lines. the defect is multiplicity dependent and greater in the macrophage cell l ...200111248062
evasion of cytotoxic t lymphocytes by murine cytomegalovirus.murine cytomegalovirus causes lifelong infections with little pathology in normal host animals. control of viral replication and prevention of pathology depend on both innate and adaptive immune mechanisms, and cytolytic t lymphocytes play a key role in this process. the virus encodes a number of genes which alter the normal assembly of class i major histocompatability complex proteins, and thus interfere with the ability of infected cells to present antigen to cd8(+)t cells. this review will ex ...200111289796
ganciclovir and cidofovir treatment of cytomegalovirus-induced myocarditis in mice.the cardiovascular disease myocarditis is characterized by inflammation and necrosis of cardiac muscle. this disease has been associated with various viral etiologies, including cytomegalovirus (cmv). murine cmv (mcmv) infection of adult balb/c mice produces a disease with acute and chronic phases similar to that found in humans. in our murine model, we have investigated the therapeutic efficacy of antiviral drug administration on myocarditis. two drugs commonly used for cmv treatment, ganciclov ...200111302808
allogeneic transplantation induces expression of cytomegalovirus immediate-early genes in vivo: a model for reactivation from latency.reactivation of cytomegalovirus (cmv) from latency is a frequent complication of organ transplantation, and the molecular mechanism by which this occurs is unknown. previous studies have shown that allogeneic stimulation induces reactivation of human cmv (hcmv) in vitro (64). we find that transplantation of vascularized allogeneic kidneys induces murine cmv (mcmv) and hcmv immediate-early (ie) gene expression. this induction is accompanied by increased expression of transcripts encoding inflamma ...200111312353
treatment of chronic sialadenitis in a murine model of sjögren's syndrome by local fasl gene transfer.infection of fas (fas/cd95)-mutant c57bl/6 (b6)-lpr/lpr mice with murine cytomegalovirus (mcmv) leads to a chronic sialadenitis similar to that of sjögren's syndrome (ss). the aim of this study was to evaluate whether chronic sialadenitis would also occur in fas ligand (fasl/cd95l)-mutant b6-gld/gld mice upon infection with mcmv and whether the expression of fasl by local gene transfer using recombinant adenoviral vectors would be an effective therapeutic strategy.200111315936
a virus finds its natural killer. 200111326263
susceptibility to mouse cytomegalovirus is associated with deletion of an activating natural killer cell receptor of the c-type lectin superfamily.cytomegalovirus is the leading cause of congenital viral disease and the most important opportunistic infection in immunocompromised patients. we have used a mouse experimental infection model (mcmv) to study the genetic parameters of host/virus interaction. susceptibility to infection with mcmv is controlled by cmv1, a chromosome 6 locus that regulates natural killer (nk) cell activity against virally infected targets. here, we use a positional cloning strategy to isolate the gene mutated at th ...200111326273
from infection to autoimmunity.we have investigated two models of virally-induced autoimmune myocarditis in mice using widely different infectious agents. infection of susceptible balb/c mice with either coxsackievirus or murine cytomegalovirus results in the development of acute myocarditis from day 7-14 after infection, and chronic myocarditis from day 28 onwards. the chronic phase of myocarditis is associated with mononuclear infiltration of the myocardium and the production of autoantibodies to cardiac myosin, although in ...200111334481
vital involvement of a natural killer cell activation receptor in resistance to viral infection.natural killer (nk) cells are lymphocytes that can be distinguished from t and b cells through their involvement in innate immunity and their lack of rearranged antigen receptors. although nk cells and their receptors were initially characterized in terms of tumor killing in vitro, we have determined that the nk cell activation receptor, ly-49h, is critically involved in resistance to murine cytomegalovirus in vivo. ly-49h requires an immunoreceptor tyrosine-based activation motif (itam)-contain ...200111340207
interleukin-4 induces mouse cytomegalovirus interstitial pneumonia in a latent infection model.to better understand immune mechanisms involved in onset of cytomegalovirus pneumonia, we initially examined the replication of a low virulence strain of mouse cytomegalovirus (mcmv) in nude and balb/c mice infected by intranasal inoculation. mcmv was detected by plaque assay in the salivary glands of nude mice from days 3 to 16, and in those of balb/c mice from days 7 to 11. nude mice became infected with mcmv earlier than balb/c mice. moreover, mcmv-dna was detected in the salivary glands unti ...200111402620
products of us22 genes m140 and m141 confer efficient replication of murine cytomegalovirus in macrophages and spleen.efficient replication of murine cytomegalovirus (mcmv) in macrophages is a prerequisite for optimal growth and spread of the virus in its natural host. simultaneous deletion of us22 gene family members m139, m140, and m141 results in impaired replication of mcmv in macrophages and mice. in this study, we characterized the proteins derived from these three genes and examined the impact of individual gene deletions on viral pathogenesis. the m139, m140, and m141 gene products were identified as ea ...200111413295
experimental preemptive immunotherapy of murine cytomegalovirus disease with cd8 t-cell lines specific for ppm83 and pm84, the two homologs of human cytomegalovirus tegument protein ppul83 (pp65).cd8 t cells are the principal antiviral effectors controlling cytomegalovirus (cmv) infection. for human cmv, the virion tegument protein ppul83 (pp65) has been identified as a source of immunodominant peptides and is regarded as a candidate for cytoimmunotherapy and vaccination. two sequence homologs of ppul83 are known for murine cmv, namely the virion protein ppm83 (pp105) expressed late in the viral replication cycle and the nonstructural protein pm84 (p65) expressed in the early phase. here ...200111413326
activation of murine cytomegalovirus immediate-early promoter in cerebral ventricular zone and glial progenitor cells in transgenic mice.cytomegalovirus (cmv) is the most common infectious cause of congenital anomalies of the cns in humans. we recently reported that the murine cytomegalovirus (mcmv) immediate-early (ie) gene promoter directs astrocyte-specific expression in adult transgenic mice. in the present study, we analyzed the activation of the mcmv ie promoter in developing transgenic mouse brains and compared the activation with that of the musashi 1 (msi1) gene, which is expressed in neural progenitor cells, including n ...200111424191
murine cytomegalovirus is regulated by a discrete subset of natural killer cells reactive with monoclonal antibody to ly49h.antiviral roles of natural killer (nk) cell subsets were examined in c57bl/6 mice infected with murine cytomegalovirus (mcmv) and other viruses, including lymphocytic choriomeningitis virus (lcmv), vaccinia virus (vv), and mouse hepatitis virus (mhv). each virus vigorously induced an nk cell infiltrate into the peritoneal cavity and liver, causing some redistributions of nk cell subsets defined by monoclonal antibody (mab) directed against ly49a, c/i, d, and g2. striking results were seen with a ...200111435470
in vitro and in vivo activity of 1-o-hexadecylpropanediol-3-phospho-ganciclovir and 1-o-hexadecylpropanediol-3-phospho-penciclovir in cytomegalovirus and herpes simplex virus infections.human cytomegalovirus (hcmv) and herpes simplex virus (hsv) can cause a wide variety of clinical manifestations in man. ganciclovir (gcv) is effective against hcmv infection when administered by the intravenous route and may be used orally in large doses for prophylaxis of hcmv infections in organ transplantation patients and in aids patients. in previous studies with acyclovir (acv), we found that covalent attachment of an alkyl glycerol phosphate moiety greatly increased oral bioavailability a ...200111437323
inactivation of lrg-47 and irg-47 reveals a family of interferon gamma-inducible genes with essential, pathogen-specific roles in resistance to infection.the cytokine interferon (ifn)-gamma regulates immune clearance of parasitic, bacterial, and viral infections; however, the underlying mechanisms are poorly understood. recently, a family of ifn-gamma-induced genes has been identified that encode 48-kd gtp-binding proteins that localize to the endoplasmic reticulum of cells. the prototype of this family, igtp, has been shown to be required for host defense against acute infections with the protozoan parasite toxoplasma gondii, but not for normal ...200111457893
the murine cytomegalovirus pp89 immunodominant h-2ld epitope is generated and translocated into the endoplasmic reticulum as an 11-mer precursor peptide.the 20s proteasome is involved in the processing of mhc class i-presented ags. a number of epitopes is known to be generated as precursor peptides requiring trimming either before or after translocation into the endoplasmic reticulum (er). in this study, we have followed the proteasomal processing and tap-dependent er translocation of the immunodominant epitope of the murine cmv immediate early protein pp89. for the first time, we experimentally linked peptide generation by the proteasome system ...200111466372
the interferon-inducible 204 gene is transcriptionally activated by mouse cytomegalovirus and is required for its replication.infection of cells with viable or uv-inactivated murine cytomegalovirus (mcmv) increased the ifn-inducible 204 gene at both the mrna and the protein levels. the activity of a reporter gene driven by the mouse ifi204 promoter induced following virus infection showed that this increase was due to transcriptional activation. moreover, facs analysis of infected mouse embryo fibroblasts (mef) stably transfected with a p204-dominant-negative mutant (p204dmmef) revealed that they do not accumulate at t ...200111485393
control of murine cytomegalovirus replication in salivary glands during acute infection is independent of the fas ligand/fas system.the course of mouse cytomegalovirus (mcmv) infection was compared between mutant c57bl/6 (b6) mice deficient in either perforin (perf-/-), or perforin, granzyme a and b (perfxgzmaxb-/-), and b6 gld mice lacking functionally active fas ligand to elucidate the contribution of the two main cytolytic pathways in the early control of mcmv infection. at 15 and 30 days post infection (p.i.) virus titers were elevated in salivary glands of perf-/- and perfxgzmaxb-/-, but almost undetectable in those of ...200111497079
murine cytomegalovirus infection induces cellular folylpolyglutamate synthetase activity in quiescent cells.cytomegalovirus (cmv) infection stimulates the expression of cellular enzymes involved in the biosynthesis of dna precursors. among them, dihydrofolate reductase (dhfr) and thymidylate synthase (ts) require folate as coenzymes. in growing cells, folates are readily converted to polyglutamated forms by the cellular enzyme folylpolyglutamate synthetase (fpgs). polyglutamated folates are selectively retained within the cell and have an increased affinity for dhfr and ts. here we report that murine ...200111509884
murine cytomegalovirus cc chemokine homolog mck-2 (m131-129) is a determinant of dissemination that increases inflammation at initial sites of infection.the murine cytomegalovirus cc chemokine homolog mck-2 (m131-129) is an important determinant of dissemination during primary infection. reduced peak levels of viremia at day 5 were followed by reduced levels of virus in salivary glands starting at day 7 when mck insertion (rm461) and point (rm4511) mutants were compared to mck-expressing viruses. a dramatic mck-2-enhanced inflammation occurred at the inoculation site over the first few days of infection, preceding viremia. the data further reinf ...200111559829
the murine cytomegalovirus immune evasion protein m4/gp34 forms biochemically distinct complexes with class i mhc at the cell surface and in a pre-golgi compartment.we have recently demonstrated that the murine cmv (mcmv) gene m4 is an immune evasion gene that protects mcmv-infected targets from some virus-specific ctl clones. m4 encodes m4/gp34, a 34-kda glycoprotein that binds to major histocompatibility complex class i in the endoplasmic reticulum and forms a detergent-stable complex that is exported to the surface of the cell. to investigate how m4/gp34 promotes ctl evasion, we analyzed the assembly and export of m4/gp34-k(b) complexes. we found that 50 ...200111564807
experimental inoculation of male mice with murine cytomegalovirus and effect on offspring.murine cytomegalovirus (mcmv) was used to examine aspects of viral infection in male mice, and its possible transmission to their offspring.200111574489
the multiple immune-evasion genes of murine cytomegalovirus are not redundant: m4 and m152 inhibit antigen presentation in a complementary and cooperative fashion.both human cytomegaloviruses (hcmvs) and murine cytomegaloviruses (mcmvs) encode multiple genes that interfere with antigen presentation by major histocompatibility complex (mhc) class i, and thus protect infected targets from lysis by virus-specific cytotoxic t lymphocytes (ctls). hcmv has been shown to encode four such genes and mcmv to encode two. mcmv m152 blocks the export of class i from a pre-golgi compartment, and mcmv m6 directs class i to the lysosome for degradation. a third mcmv gene ...200111581318
nk cell functions restrain t cell responses during viral infections.nk cell functions for regulation of t cell responses were evaluated during acute viral infections. in vivo depletion studies established that the presence of nk cells in murine cytomegalovirus (mcmv)-infected immunocompetent mice negatively affected cd4 and cd8 t cell ifn-gamma expression, bromodeoxyuridine (brdu) incorporation, and expansion. to evaluate nk cell effects, under conditions when nk cells do not control viral replication, experiments were performed using lymphocytic choriomeningiti ...200111592081
serum of cytomegalovirus-infected mice induces monocyte chemoattractant protein-1 expression by endothelial cells.inflammation plays a central role in atherogenesis. it was hypothesized that infection of apolipoprotein e-deficient mice with murine cytomegalovirus (mcmv) increases serum levels of proinflammatory cytokines, which may induce "proatherosclerotic" changes in endothelial cells (ecs). serum samples were collected from uninfected and infected mice. elisa was used to determine cytokine serum levels and monocyte chemoattractant protein-1 (mcp-1) levels in the supernatant of mouse ecs incubated with s ...200111598832
lymphotoxins and cytomegalovirus cooperatively induce interferon-beta, establishing host-virus détente.tumor necrosis factor (tnf)-related cytokines regulate cell death and survival and provide strong selective pressures for viruses, such as cytomegalovirus (cmv), to evolve counterstrategies in order to persist in immune-competent hosts. signaling by the lymphotoxin (lt)-beta receptor or tnf receptor-1, but not fas or trail receptors, inhibits the cytopathicity and replication of human cmv by a nonapoptotic, reversible process that requires nuclear factor kappa b (nf-kappa b)-dependent induction ...200111672543
analysis of in situ nk cell responses during viral infection.nk cells are required for early control of murine cmv (mcmv) infection, but the distribution of murine nk cells in situ has not been clearly defined. we tested the reactivity of all available nk cell receptor-specific mabs by immunohistochemistry. only one mab, 4d11 (anti-ly-49g2), was reactive with c57bl/6 tissue sections. mab 4d11-reactive cells expressed the nuclear morphology and flow cytometric profile of nk cells. in lymphoid organs, nk cells were distributed primarily in the splenic red p ...200111673544
nitric oxide targets bronchiolar epithelial cells in murine cytomegalovirus-associated disease in lungs that are free of the virus.at 4 weeks after intraperitoneal (i.p.) injection of 0.2ld50 (50% lethal dose) of murine cytomegalovirus (mcmv) in adult balb/c mice, productive virus and the viral dna were detected only in the salivary glands, but not in the lungs. a single i.p. injection of anti-cd3 mab to these mice provoked pulmonary lesions, which included a thickening of the interstitium and peribronchiolar areas, accompanied with a cellular infiltration in those areas. as a result, half of the mice died. in a histochemic ...200111676413
cytomegalovirus infection and proinflammatory cytokine activation modulate the surface immune determinant expression and immunogenicity of cultured murine extrahepatic bile duct epithelial cells.murine extrahepatic bile duct epithelial cells (mebec) were isolated from extrahepatic bile ducts of balb/c mice and established in primary culture. the epithelial origin was confirmed by positive cytokeratin 19 staining for these cells and the presence of microvilli and tight junctions under electron microscopy. by immunofluorescent staining with monoclonal antibodies and flow-cytometric analysis, mebec in culture constitutively express low levels of intercellular adhesion molecule (icam)-1, cl ...200111678903
secreted virus-encoded proteins reflect murine cytomegalovirus productivity in organs.mouse infection with murine cytomegalovirus (mcmv) is an established model for studying human cytomegalovirus infection. in this study, the relationship was analyzed between mcmv activity in organs of infected mice and the presence of infectious virus (viremia), viral genomes (dnaemia), or secreted virus-encoded proteins in the blood. for the latter, 2 recombinant viruses were constructed that encode for the hepatitis b virus surface antigen and the secreted alkaline phosphatase, respectively, a ...200111679922
viral escape mechanisms--escapology taught by viruses.viruses have 'studied' immunology over millions of years of coevolution with their hosts. during this ongoing education they have developed countless mechanisms to escape from the host's immune system. to illustrate the most common strategies of viral immune escape we have focused on two murine models of persistent infection, lymphocytic choriomeningitis virus (lcmv) and murine cytomegalovirus (mcmv). lcmv is a fast replicating small rna virus with a genome prone to mutations. therefore, lcmv es ...200111703537
mouse type i ifn-producing cells are immature apcs with plasmacytoid morphology.we show here that mouse interferon-alpha (ifn-alpha)-producing cells (mipcs) are a unique subset of immature antigen-presenting cells (apcs) that secrete ifn-alpha upon stimulation with viruses. mipcs have a plasmacytoid morphology, can be stained with an antibody to ly6g and ly6c (anti-ly6g/c) and are ly6c+b220+cd11clocd4+; unlike other dendritic cell subsets, however, they do not express cd8alpha or cd11b. although mipcs undergo apoptosis in vitro, stimulation with viruses, ifn-alpha or cpg ol ...200111713464
two antigenic peptides from genes m123 and m164 of murine cytomegalovirus quantitatively dominate cd8 t-cell memory in the h-2d haplotype.the importance of cd8 t cells for the control of cytomegalovirus (cmv) infection has raised interest in the identification of immunogenic viral proteins as candidates for vaccination and cytoimmunotherapy. the final aim is to determine the viral "immunome" for any major histocompatibility complex class i molecule by antigenicity screening of proteome-derived peptides. for human cmv, there is a limitation to this approach: the t cells used as responder cells for peptide screening are usually memo ...200211739681
immunomodulation of murine cytomegalovirus-induced myocarditis in mice treated with lipopolysaccharide and tumor necrosis factor.murine cytomegalovirus (mcmv) infection of balb/c mice produces acute and chronic myocarditis similar to clinical disease in humans. in contrast, mcmv-infected c57bl/6 mice develop only mild acute myocarditis. we have investigated the effect of administration of the immunomodulator lipopolysaccharide (lps) on the development of postviral myocarditis in mice. lps exacerbated heart inflammation in both strains of mcmv-infected mice, with normally resistant c57bl/6 mice developing chronic myocardit ...200111747356
murine cytomegalovirus m02 gene family protects against natural killer cell-mediated immune surveillance.the murine cytomegalovirus m02 gene family encodes putative type i membrane glycoproteins named m02 through m16. a subset of these genes were fused to an epitope tag and cloned into an expression vector. in transfected and murine cytomegalovirus-infected cells, m02, m04, m05, m06, m07, m09, m10, and m12 localized to cytoplasmic structures near the nucleus, whereas m08 and m13 localized to a filamentous structure surrounding the nucleus. substitution mutants lacking the m02 gene (smsubm02) or the ...200211752177
the rat cytomegalovirus r33-encoded g protein-coupled receptor signals in a constitutive fashion.the rat cytomegalovirus (rcmv) r33 gene is conserved among all betaherpesviruses and encodes a protein (pr33) that shows sequence similarity with chemokine-binding g protein-coupled receptors (gpcrs). previously, the physiological significance of the r33 gene was demonstrated by the finding that an rcmv strain with r33 deleted is severely attenuated in vivo and is unable to either enter or replicate in the salivary glands of infected rats. here, we report that rcmv pr33 is expressed as a functio ...200211773407
early gene m18, a novel player in the immune response to murine cytomegalovirus.the identification of all antigenic peptides encoded by a pathogen, its t cell 'immunome', is a research aim for rational vaccine design. screening of proteome-spanning peptide libraries or computational prediction is used to identify antigenic peptides recognized by cd8 t cells. based on their high coding capacity, cytomegaloviruses (cmvs) could specify numerous antigenic peptides. yet, current evidence indicates that the memory cd8 t cell response in a given haplotype is actually focused on a ...200211807223
strong cd8 t-cell responses following coimmunization with plasmids expressing the dominant pp89 and subdominant m84 antigens of murine cytomegalovirus correlate with long-term protection against subsequent viral challenge.we previously showed that intradermal immunization with plasmids expressing the murine cytomegalovirus (mcmv) protein ie1-pp89 or m84 protects against viral challenge and that coimmunization has a synergistic protective effect (c. s. morello, l. d. cranmer, and d. h. spector, j. virol. 74:3696-3708, 2000). using an intracellular gamma interferon cytokine staining assay, we have now characterized the cd8+ t-cell response after dna immunization with pp89, m84, or pp89 plus m84. the pp89- and m84-s ...200211836387
interferon alpha/beta and interleukin 12 responses to viral infections: pathways regulating dendritic cell cytokine expression in vivo.interferon (ifn)-alpha/beta and interleukin (il)-12 are cytokines critical in defense against viruses, but their cellular sources and mechanisms of regulation for in vivo expression remain poorly characterized. the studies presented here identified a novel subset of dendritic cells (dcs) as major producers of the cytokines during murine cytomegalovirus (mcmv) but not lymphocytic choriomeningitis virus (lcmv) infections. these dcs differed from those activated by toxoplasma antigen but were relat ...200211854364
tumor control in a model of bone marrow transplantation and acute liver-infiltrating b-cell lymphoma: an unpredicted novel function of cytomegalovirus.tumor relapse and cytomegalovirus (cmv) infection are major concerns in the therapy of hematopoietic malignancies by bone marrow transplantation (bmt). little attention so far has been given to a possible pathogenetic interplay between cmv and lymphomas. cmv inhibits stem cell engraftment and hematopoietic reconstitution. thus, by causing maintenance of bone marrow aplasia and immunodeficiency, cmv could promote tumor relapse. alternatively, cmv could aid tumor remission. one might think of cyto ...200211861853
failure to infect embryos after virus injection in mouse zygotes.the intracytoplasmic injection of sperm raises the problem that viral elements may be transported into the oocyte by the spermatozoon or the surrounding medium. it also raises questions about how the developing zygote will behave.200211870132
cutting edge: inhibitory functions of the killer cell lectin-like receptor g1 molecule during the activation of mouse nk cells.the killer cell lectin-like receptor g1 (klrg1) is the mouse homolog of the rat mast cell function-associated ag and contains an immunoreceptor tyrosine-based inhibitory motif in its cytoplasmic domain. in this study we demonstrate that both pathogenic and nonpathogenic in vivo activation of nk cells induces the expression of klrg1 on their cell surface. upon infection with murine cmv, this induction peaks between days 5 and 7 with about 90% of the nk cells expressing klrg1. on day 1.5 post-muri ...200211884419
identification and characterization of novel murine cytomegalovirus m112-113 (e1) gene products.the human cytomegalovirus (hcmv) ul112-113 gene products play important roles in viral dna replication and transcriptional regulation. in this report, we characterize two novel transcripts originating from the homologous m112-113 (e1) region of the murine cytomegalovirus (mcmv) genome. these transcripts of 2.0 and 2.4 kb represent alternatively spliced products of the e1 gene region. analysis of the e1 proteins demonstrates the presence of a previously unidentified 87-kda protein that is likely ...200211886278
broad-spectrum antiviral activity of pnu-183792, a 4-oxo-dihydroquinoline, against human and animal herpesviruses.we identified a novel class of 4-oxo-dihydroquinolines represented by pnu-183792 which specifically inhibit herpesvirus polymerases. pnu-183792 was highly active against human cytomegalovirus (hcmv, ic(50) value 0.69 microm), varicella zoster virus (vzv, ic(50) value 0.37 microm) and herpes simplex virus (hsv, ic(50) value 0.58 microm) polymerases but was inactive (ic(50) value >40 microm) against human alpha (alpha), gamma (gamma), or delta (delta) polymerases. in vitro antiviral activity again ...200211888654
characterization of the murine cytomegalovirus 38 kda m137 gene product.murine cytomegalovirus (mcmv) m137 null mutants, deltam137a and deltam137b, were generated by inserting a gpt cassette into a deleted region of the open reading frame. a polyclonal antiserum produced to an escherichia coli expressed gst-m137 fusion protein was used to show that a 38 kda polypeptide corresponding to the predicted m137 gene product was present in nih 3t3 fibroblasts infected with wild-type mcmv but was not detected in deltam137 infected cells. the protein did not fractionate with ...200211900850
direct recognition of cytomegalovirus by activating and inhibitory nk cell receptors.natural killer (nk) cells express inhibitory receptors for major histocompatibility complex (mhc) class i antigens, preventing attack against healthy cells. mouse cytomegalovirus (mcmv) encodes an mhc-like protein (m157) that binds to an inhibitory nk cell receptor in certain mcmv-susceptible mice. in mcmv-resistant mice, this viral protein engages a related activating receptor (ly49h) and confers host protection. these activating and inhibitory receptors are highly homologous, suggesting the po ...200211950999
development of a vaccine against murine cytomegalovirus (mcmv), consisting of plasmid dna and formalin-inactivated mcmv, that provides long-term, complete protection against viral replication.we previously demonstrated that immunization of mice with plasmid dnas (pdnas) expressing the murine cytomegalovirus (mcmv) genes ie1-pp89 and m84 provided synergistic protection against sublethal viral challenge, while immunization with plasmids expressing putative virion proteins provided no or inconsistent protection. in this report, we sought to augment protection by increasing the breadth of the immune response. we identified another mcmv gene (m04 encoding gp34) that provided strong and co ...200211967299
intra-abdominal bacterial infection reactivates latent pulmonary cytomegalovirus in immunocompetent mice.critically ill surgery patients are susceptible to pulmonary reactivation of latent cytomegalovirus (cmv), but what triggers this reactivation is unknown. immunosuppression and bacterial sepsis are thought to stimulate reactivation of cmv, and in this study it was hypothesized that immunosuppressive effects of surgery with or without concomitant bacterial infection may reactivate latent cmv. mice infected with cmv were allowed to develop latent infections. latently infected mice underwent a lapa ...200211992273
immunisation of balb/c mice with severely attenuated murine cytomegalovirus mutants induces protective cellular and humoral immunity.previously, we showed that two temperature-sensitive mutants of murine cytomegalovirus (tsm5 and tsm30) expressed immediate-early (ie-1), early (e-1), and late (gb) phase genes in the tissues of immunocompetent balb/c mice, yet failed to produce infectious progeny virus in any tissue at any time at 1-21 days post-infection. mice inoculated intraperitoneally with tsm5 became latently infected, but this latent virus could not be reactivated as an infectious virus after immunosuppression, although ...200211992579
immunology. a pathogen receptor on natural killer cells. 200212016296
processing and presentation of murine cytomegalovirus porfm164-derived peptide in fibroblasts in the face of all viral immunosubversive early gene functions.cd8 t cells are the principal effector cells in the resolution of acute murine cytomegalovirus (mcmv) infection in host organs. this undoubted antiviral and protective in vivo function of cd8 t cells appeared to be inconsistent with immunosubversive strategies of the virus effected by early (e)-phase genes m04, m06, and m152. the so-called immune evasion proteins gp34, gp48, and gp37/40, respectively, were found to interfere with peptide presentation at different steps in the major histocompatib ...200212021337
persistent rat cytomegalovirus (rcmv) infection of the salivary glands contributes to the anti-rcmv humoral immune response.the salivary glands are the major sites of persistent replication of rat cytomegalovirus (rcmv). at several months post infection (pi), infectious rcmv is usually still produced in the salivary glands but not in any other organ or tissue of the rat. to investigate whether the persistence of rcmv in the salivary glands is crucial to the pathogenesis of viral infection, we monitored the progression of rcmv-induced disease in rats from which the salivary glands had been surgically removed (desaliva ...200212034483
a rat cytomegalovirus strain with a disruption of the r144 mhc class i-like gene is attenuated in the acute phase of infection in neonatal rats.we previously generated an rcmv strain in which the r144 gene, encoding a major histocompatibility complex class i homolog, had been deleted (rcmvdelta r144). to investigate the role of r144 during acute infection of neonatal rats, we infected three days-old neonatal rats with either rcmvdelta r144 or wild type (wt) rcmv and the presence of infectious virus as well as viral dna in various organs was determined at either 3, 5 or 21 days p.i.. in addition, we assessed both type and number of infla ...200212038690
mechanisms of human cytomegalovirus persistence and latency.human cytomegalovirus (hcmv) is a ubiquitous beta-herpesvirus that causes severe disease primarily in immunosuppressed individuals. a major characteristic of hcmv with obvious clinical importance is the ability of the virus to establish lifelong infection within the host following the initial acute infection. one strategy used by hcmv to maintain itself within the host is the establishment of cellular sites of persistent infection and viral latency. recent studies have identified endothelial cel ...200212045013
recognition of a virus-encoded ligand by a natural killer cell activation receptor.natural killer (nk) cells express inhibitory and activation receptors that recognize mhc class i-like molecules on target cells. these receptors may be involved in the critical role of nk cells in controlling initial phases of certain viral infections. indeed, the ly49h nk cell activation receptor confers in vivo genetic resistance to murine cytomegalovirus (mcmv) infections, but its ligand was previously unknown. herein, we use heterologous reporter cells to demonstrate that ly49h recognizes mc ...200212060703
reactivation of latent cytomegalovirus infection in mouse brain cells detected after transfer to brain slice cultures.cytomegalovirus (cmv) is the most significant infectious cause of brain disorders in humans involving the developing brain. it is hypothesized that the brain disorders occur after recurrent reactivation of the latent infection in some kinds of cells in the brains. in order to test this hypothesis, we examined the reactivation of latent murine cmv (mcmv) infection in the mouse brain by transfer to brain slice culture. we infected neonatal and young adult mice intracerebrally with recombinant mcmv ...200212072524
antiviral and immunomodulatory activity of the metal chelator ethylenediaminedisuccinic acid against cytomegalovirus in vitro and in vivo.antiviral activity of the metal chelator ethylenediaminedisuccinic acid (edds) was examined in vitro against human cytomegalovirus (hcmv) wild type strains and strains that are resistant against ganciclovir (gcv) and cidofovir (hpmpc). edds inhibited the replication of wild-type as well as gcv- and hpmpc-resistant strains with a 50% effective concentration of 7.4-12 microg/ml. at concentrations of 100 microg/ml edds, unlike gcv or hpmpc, suppressed hcmv-induced up-regulation of intercellular adh ...200212076762
the murine cytomegalovirus immunomodulatory gene m152 prevents recognition of infected cells by m45-specific ctl but does not alter the immunodominance of the m45-specific cd8 t cell response in vivo.although in vitro studies have shown that herpesviruses, including murine cmv (mcmv), encode genes that interfere with the mhc class i pathway, their effects on the ctl response in vivo is unclear. we identified a d(b)-restricted ctl epitope from mcmv m45 by screening an mcmv genomic library using ctl clones isolated from mice infected with mcmv lacking m152. because m152 severely inhibits ctl recognition of m45 in vitro, we questioned whether an m45-specific response would be generated in mice ...200212077265
viral latency: a link between myocarditis and dilated cardiomyopathy? 200212099707
type i interferon gene therapy protects against cytomegalovirus-induced myocarditis.type i interferons (ifns) are produced early in response to viral infection and modulate adaptive immunity. previously we demonstrated localized protection against murine cytomegalovirus (mcmv) infection in ifn dna-inoculated mice. here we examine the effect of seven ifn subtypes (ifna1, a2, a4, a5, a6, a9 and b), administered by dna inoculation, on systemic mcmv infection and myocarditis. ifn transgene expression altered the pathogenesis of mcmv infection with regard to virus titre and myocardi ...200212100732
virology. cmv makes a timely exit. 200212161637
cytomegalovirus recruitment of cellular kinases to dissolve the nuclear lamina.the passage of large-sized herpesviral capsids through the nuclear lamina and the inner nuclear membrane to leave the nucleus requires a dissolution of the nuclear lamina. here, we report on the functions of m50/p35, a beta-herpesviral protein of murine cytomegalovirus. m50/p35 inserts into the inner nuclear membrane and is aggregated by a second viral protein, m53/p38, to form the capsid docking site. m50/p35 recruits the cellular protein kinase c for phosphorylation and dissolution of the nucl ...200212161659
type i interferons regulate inflammatory cell trafficking and macrophage inflammatory protein 1alpha delivery to the liver.macrophage inflammatory protein 1alpha (mip-1alpha, ccl3) is critical for liver nk cell inflammation and delivery of ifn-gamma to mediate downstream protective responses against murine cytomegalovirus (mcmv) infections. this system was used to evaluate the upstream contribution of the type 1 ifns, ifn-alpha/beta, in promotion of mip-1alpha production. mice deficient in ifn-alpha/beta functions, as a result of mutation in the receptor for these cytokines (ifn-alpha/betar(-)), were profoundly defi ...200212163451
enhanced cytomegalovirus infection of developing brain independent of the adaptive immune system.cytomegalovirus (cmv) has been suggested as the most prevalent infectious agent causing neurological dysfunction in the developing brain; in contrast, cmv infections are rare in the adult brain. one explanation generally given for the developmental susceptibility to the virus is that the developing immune system is too immature to protect the central nervous system from viral infection, but as the immune system develops it can protect the brain. we suggest an alternate view: that developing brai ...200212163604
persisting murine cytomegalovirus can reactivate and has unique transcriptional activity in ocular tissue.cytomegalovirus (cmv) retinitis is an important ocular complication in human immunodeficiency virus-infected individuals and the leading cause of blindness in those not undergoing highly active antiretroviral therapy. murine cmv (mcmv) infection of mice has been shown to be a useful small-animal model for the study of cmv pathogenesis in the eye. the purpose of this study was to evaluate cmv persistence in ocular tissue and to determine the potential for reactivation. following subretinal inocul ...200212186900
ecological basis for fertility control in the house mouse (mus domesticus) using immunocontraceptive vaccines.laboratory studies confirm the potential for fertility control in the house mouse mus domesticus using mouse cytomegalovirus (mcmv) as a vector for an immunocontraceptive vaccine. this article presents an overview of key results from research in australia on enclosed and field populations of mice and the associated epidemiology of mcmv. the virus is geographically widespread in australia. it also persists in low population densities of mice, although if population densities are low for at least ...200212220162
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