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intraocular viral replication after systemic murine cytomegalovirus infection requires immunosuppression.human cytomegalovirus retinitis is the most common blinding complication of acquired immune deficiency syndrome. however, the pathogenesis of the disease is poorly understood. the authors sought to characterize intraocular viral replication after systemic murine cytomegalovirus (mcmv) infection in the normal and immunosuppressed balb/c mouse.19957558728
induction of protective cytotoxic t cells to murine cytomegalovirus by using a nonapeptide and a human-compatible adjuvant (montanide isa 720).the use of synthetic peptides representing cytotoxic t-cell (ctl) epitopes for human vaccination requires the identification of a suitable adjuvant formulation. a single immunization with montanide isa720/tetanus toxoid/yphfmptnl protected mice against murine cytomegalovirus and induced epitope-specific ctl. such formulations will find application in peptide-based ctl anti-viral vaccines.19957815511
the potential of murine cytomegalovirus as a viral vector for immunocontraception.wild populations of house mice (mus domesticus) regularly undergo population eruptions in the cereal growing regions of s.e. australia, causing significant damage to crops. rodenticides are costly and are of limited usefulness, and the need for a biological control agent is widely recognized. the options for the use of an infectious agent to control mouse populations are considered. the three main types are: infectious agents which establish lethal infection; those which directly interfere with ...19947831489
murine cytomegalovirus-associated arteritis.unique inflammatory lesions affecting the ascending aorta and pulmonary artery of balb/c and c57bl/6 mice infected with murine cytomegalovirus (mcmv) were identified in a pilot and two subsequent experiments to characterize the potential effect of mcmv infection on diet-induced atherosclerotic lesions. suckling balb/c and c57bl/6 mice were inoculated with mcmv and subsequently fed either a commercial mouse diet or a synthetic atherogenic diet from weaning. the three experiments varied with respe ...19957771052
identification and molecular characterization of the murine cytomegalovirus homolog of the human cytomegalovirus ul100 gene.the ul100 gene of human cytomegalovirus (hcmv) has been shown to encode an envelope glycoprotein that might play an important role in hcmv infection. using the hcmv ul100 gene as a probe in low stringency hybridization studies, we were able to identify the putative ul100 homologous gene of murine cytomegalovirus (mcmv), strain smith. the mcmv gene was sequenced and localized to the left end of the ecori fragment h on the mcmv physical map. this genomic location is similar to that found for the h ...19957653096
analysis of the role of cd4+ t-cells during murine cytomegalovirus infection in different strains of mice.we examined the role of cd4+ t-cells in peritoneal exudate cells (pecs) during the course of acute murine cytomegalovirus (mcmv) infection in two strains of mice. cell counts of pecs and cytofluorometric analysis showed that c57bl/6, a resistant strain, had more cd4+ t-cells than balb/c, a susceptible strain, after intraperitoneal infection of 3 x 10(3) pfu of the smith strain of mcmv, though both strains had an equivalent number of cd8+ t-cells. cd4+ t-cells of both strains expressed mrna of if ...19957653101
nk cell response to viral infections in beta 2-microglobulin-deficient mice.because class i mhc ags have been implicated as modulators of target cell sensitivity to nk cell-mediated lysis, the regulation of virus infections and the fate of nk cells and their natural targets was examined in beta 2-microglobulin-deficient mice, which have defective class i mhc expression. infections with either the nk cell-sensitive murine cytomegalovirus (mcmv) or the nk cell-resistant lymphocytic choriomeningitis virus (lcmv) significantly augmented nk cell activity in either c57bl/6 (+ ...19957529286
induction of apoptosis of t cells by infecting mice with murine cytomegalovirus.cytomegalovirus (cmv) is associated with several lymphocyte dysfunctions, but the precise mechanisms of the dysfunctions are still unclear. to elucidate the mechanisms, a cell cycle-dna content analysis was performed on splenic t cells of murine cmv (mcmv)-infected balb/c mice. t cells from mice infected with 3 x 10(3) pfu of mcmv contained a higher percentage of hypodiploid nuclei after 12 or 24 h of culture than those from naive mice. t cells from infected mice also contained a larger amount o ...19957609043
antiviral activity of nk 1.1+ natural killer cells in c57bl/6 scid mice infected with murine cytomegalovirus.the activation, proliferation, and antiviral effects of natural killer (nk) cells were examined in a newly developed stock of mice, c57bl/6jsz mice homozygous for the severe combined immunodeficiency (scid) mutation. these mice lack functional t and b cells and express the nk 1.1 alloantigen. such nk 1.1 expression facilitates the analysis of nk cells and their depletion in vivo with a monoclonal anti-nk 1.1 antibody. these mice, therefore, provide an excellent model to examine unambiguously the ...19947833623
mapping and transcriptional analysis of the murine cytomegalovirus homologue of the human cytomegalovirus ul103 open reading frame.murine cytomegalovirus (mcmv) has been widely used as a model for human cytomegalovirus (hcmv) infection since the two viruses share many biological and pathogenic properties. to further evaluate the similarities in the genomes of these viruses we have sought to identify mcmv genes that encode immunoreactive proteins by screening a lambda gt11 cdna library with anti-mcmv monoclonal antibodies (mab). clone 430, identified on the basis of its reactivity with the mab 6/20/1, was completely sequence ...19947941355
nucleotide analogs related to acyclovir and ganciclovir are effective against murine cytomegalovirus infections in balb/c and severe combined immunodeficient mice.acyclovir phosphonate [9-(3-phosphono-propyloxymethyl)guanine; sr3722] and the s enantiomer (sr3772), r enantiomer (sr3773), and r,s enantiomeric mixture (sr3745a) of ganciclovir phosphonate (9-[((+/-)-1-hydroxymethyl-3-phosphono)propyloxymethyl]guanine) were evaluated for their antiviral activities against murine cytomegalovirus. in severe combined immunodeficient mice infected with murine cytomegalovirus, sr3773 and sr3745a (12.5, 25, and 50 mg/kg of body weight per day) were superior to ganci ...19947811037
mouse cytomegalovirus reactivation in severe combined immune deficient mice after implantation of latently infected salivary gland.the hypothesis that replication-competent mouse cytomegalovirus (mcmv) is detectable in severe combined immunodeficient (scid) mice after implantation of latently infected tissue was examined. sections of latently infected salivary gland from 5 balb/c mice were implanted into 20 c.b-17 scid mice. recipient scid mice were sacrificed weekly for 5 weeks, and mcmv infection was detected in target organs using culture and dna polymerase chain reaction (pcr). all donors were negative by standard cultu ...19957622898
bone marrow atrophy induced by murine cytomegalovirus infection.acute, sublethal infection of mice with murine cytomegalovirus (mcmv) resulted in up to 80% decreases in the number of cells recoverable from the bone marrow, and a decrease in peripheral blood leucocyte counts during the first week of infection. depopulation of the leucopoietic areas of the marrow was evident from examination of histological sections. the severity of bone marrow atrophy in mcmv-infected mice of different strains correlated with previously described genetically determined sensit ...19947959876
expression of a murine cytomegalovirus early-late protein in "latently" infected mice.monoclonal antibodies were isolated from the spleen of a latently infected mouse to identify possible antigenic markers for latent murine cytomegalovirus infection. one antibody, am3, was selected for further study. characterization of the antigen recognized by am3 confirmed that it is the early-late phosphoprotein pp50. the antigen was readily detected by immunoautoradiography in the spleens of acutely and latently infected mice. low levels of the am3/pp50 transcript were also detected in laten ...19957622880
dna sequence and transcriptional analysis of the glycoprotein m gene of murine cytomegalovirus.we have characterized the gene encoding the murine cytomegalovirus (mcmv) homologue of the human cytomegalovirus (hcmv) ul100 open reading frame (orf) that encodes the hcmv glycoprotein m (gm) molecule. it was identified based on its collinearity with mcmv homologues of the hcmv ul99, ul102, ul103 and ul104 orfs which lie in the hindiii g fragment of the k181 strain of mcmv. sequencing of a 2.3 kb ecori-bamhi subfragment of the ecori g fragment adjacent to the ecori a fragment revealed the prese ...19957595401
mhc proteins and heparan sulphate proteoglycans regulate murine cytomegalovirus infection.factors influencing mcmv infection mediated by mhc class 1 molecules were analysed further as previous studies showed that the effects of the mhc genotype on sensitivity to this virus are important in vivo. here we show that h-2d, h-2b, h-2r and h-2v macrophages are highly sensitive to mcmv. moreover, transfection of h-2k l-cells with kb or dd conferred sensitivity to mcmv. this was not affected by amino acid substitutions in kb alpha 1 or alpha 2, although previous studies demonstrated that exc ...19957493766
requirement for natural killer cell-produced interferon gamma in defense against murine cytomegalovirus infection and enhancement of this defense pathway by interleukin 12 administration.the presence of natural killer (nk) cells contributes to early defense against murine cytomegalovirus (mcmv) infection. although nk cells can mediate in vivo protection against mcmv, the mechanism by which they do so has not been defined. the studies presented here evaluate cytokine production by nk cells activated during mcmv infection and the role of nk cell-produced cytokines in early in vivo antiviral defenses. experiments with normal c57bl/6, t cell-deficient c57bl/6 nude, and severe combin ...19957561678
effect of a retroviral immunodeficiency syndrome on resistance to mcmv: a role for natural killer cells.mice exhibiting t cell immunodeficiency and lymphadenopathy induced by lp-bm5 mulv (maids) were assessed for their ability to control murine cytomegalovirus (mcmv) infection. elevated replication of mcmv was observed in spleens 4-6 days after mcmv infection. production of interferon alpha/beta in response to mcmv was abrogated by maids and natural killer (nk) cell activity, assessed by lysis of yac-1 target cells, was correspondingly depressed on day 1. however, this was elevated at later times. ...19957552475
characterization of a conserved gene block in the murine cytomegalovirus genome.the nucleotide sequence between the lytic origin and the gh gene of the murine cytomegalovirus genome (map units 0.416-0.455) was determined. five of the 15 open reading frames identified encode polypeptides, which exhibit significant homology to polypeptides of human cytomegalovirus (hcmv) (ul69, ul71, and ul73) and to polypeptides of several other herpesviruses (dutpase and helicase/primase). the location in the genome of the five open reading frames and their direction of transcription is per ...19957483291
antiviral activities of nucleosides and nucleotides against wild-type and drug-resistant strains of murine cytomegalovirus.resistance of human cytomegalovirus to approved antiviral drugs is becoming a problem of increasing concern. in order to further study drug resistance in a related virus, strains of murine cytomegalovirus (mcmv) have been prepared in vitro by extensive adaptation of the virus to increasingly higher concentrations of either ganciclovir, foscarnet, or (s)-9-(3-hydroxy-2-[phosphonylmethoxy]propyl)cytosine (hpmpc). plaque reduction 50% effective concentrations (ec50) for the above inhibitors increas ...19957741517
cloning, characterization, and expression of the murine cytomegalovirus homologue of the human cytomegalovirus 28-kda matrix phosphoprotein (ul99).we have identified, characterized, and expressed in bacteria and recombinant vaccinia viruses a protein which likely represents the murine cytomegalovirus (mcmv) homologue of the human cytomegalovirus (hcmv) 28-kda matrix phosphoprotein, the product of the hcmv ul99 open reading frame (orf). this protein, referred to as the mcmv ul99, is encoded by a 336-nucleotide orf within the hindiii g fragment of mcmv strain smith (k181). using a dna probe that corresponded to the amino terminus of the orf, ...19947975245
a murine cytomegalovirus-neutralizing monoclonal antibody exhibits autoreactivity and induces tissue damage in vivo.the autoreactivity of murine cytomegalovirus (mcmv)-neutralizing monoclonal antibody (mab) ac1 was examined in vitro and in vivo. both mab ac1 and a human antiserum reactive with u1-small nuclear ribonucleoprotein (u1-snrnp) stained uninfected mouse embryo fibroblasts (mef) in a speckled nuclear pattern and reacted with 70,000 molecular weight (mw) mef nuclear antigens by immunoblotting, suggesting that mab ac1 cross-reacted with the 70,000 mw component of u1-snrnp. however, only mab ac1 cross-r ...19947515848
influence of the endocrine environment on herpes virus infection in rat lacrimal gland acinar cells. 19948030474
efficacy of ganciclovir in combination with zidovudine against cytomegalovirus in vitro and in vivo.in cultured mrc-5 cells, ganciclovir (gcv) alone had good activity against both the established ad169 strain (ic50 8 and 9 microm) and a clinical isolate (ic50 14 microm) of human cytomegalovirus (cmv), while 3'-azido-3'-deoxythymidine (azt) was relatively inactive [ic50 508 and > 800 (ad169 strain); > 800 microm (clinical isolate)]. when reductions in plaques were compared against reductions in the cellular metabolism of mtt at all gcv and azt combination concentrations using an improved 3-dime ...19938215302
effects of tumor necrosis factor-alpha treatment on mortality in murine cytomegalovirus-infected mice.the effects of treatment with recombinant dna-derived tumor necrosis factor-alpha (tnf-alpha) in a murine model of cytomegalovirus infection were investigated. treatment of 3-week-old swiss webster mice with murine tnf-alpha prior to infection with murine cytomegalovirus (mcmv) had no demonstrable effect on mortality. however, if mice were treated prior to infection with a combination of murine ifn-gamma and murine tnf-alpha, the dose of ifn-gamma required to achieve significant reduction in mor ...19938215304
host defense mechanisms against murine cytomegalovirus infection induced by poly i:c in severe combined immune deficient (scid) mice.the role of host defense mechanism against murine cytomegalovirus (mcmv) infection in mice with severe combined immunodeficiency (scid) was investigated using polyinosinic:polycytidylic acid (poly i:c) as a nonspecific stimulator of the immune system. when administered ip at doses of 3.7 or 15 mg/kg 18 hr prior to infection of scid mice with 10(3) or 10(4) plaque-forming units of mcmv, poly i:c significantly increased the animals' life span. poly i:c enhanced, in a dose-dependent manner (0.01-1 ...19947524103
isolation and preliminary characterisation of twenty-five temperature-sensitive mutants of mouse cytomegalovirus.to study the pathogenicity of mouse cytomegalovirus (mcmv) and to identify virulence determinants, we have isolated and phenotypically characterised 25 temperature-sensitive (ts) mutants. six of these (tsm9, tsm13, tsm20, tsm22, tsm28 and tsm30) failed to replicate in mice and were avirulent. five mutants (tsm14, tsm18, tsm19, tsm25 and tsm27) were of similar virulence to the parental wild-type (wt) virus, five (tsm7, tsm15, tsm24, tsm26 and tsm31) were 12-100 fold less virulent, five (tsm8, tsm ...19938270190
selective inhibition of cytomegaloviruses by 9-(3'-ethylphosphono-1'-hydroxymethyl-1'-propyloxy-methyl)g uanine.9-(3'-ethylphosphono-1'-hydroxymethyl-1'-propyloxy-methyl)gu anine (sr 3727a) was significantly inhibitory to strain ad169 of human cytomegalovirus (hcmv) utilizing plaque reduction and inhibition of intra- and extracellular virus yield in mrc-5 cells. the 50% effective concentrations (ec50) ranged from 6-17 microm for three laboratory strains of hcmv, whereas the 50% cytotoxic doses were > 4200 microm as determined by viable cell assay and inhibition of radiolabeled precursors into dna, rna and ...19938250544
developmental disorders of the mouse brain induced by murine cytomegalovirus: animal models for congenital cytomegalovirus infection.developmental disorders induced by congenital cytomegalovirus (cmv) infection mainly involve the central nervous system. the type and degree of the brain disorders seems to depend on infection time during gestation, virulence, route of infection and viral susceptible cells in each embryonal stage. since transplacental transmission has been reported not to occur with murine cmv (mcmv), we developed mouse models for congenital cmv infection by surgical injection of mcmv into the mouse conceptus or ...19957742931
new inhibitors of cytomegalovirus replication: in vitro evaluation, mechanism of action, and in vivo activity.human cytomegalovirus (hcmv) infections are a major cause of mortality and morbidity in human transplant recipients and a serious problem in patients with aids. furthermore, cmv is the most frequent viral cause of congenital abnormalities. two drugs are currently licensed for the treatment of severe cmv infections, i.e. ganciclovir (cymevene) and foscarnet (foscavir). however, both compounds may give severe side-effects, and resistant strains may emerge during long-term therapy. therefore, the d ...19947892749
restoration of murine cytomegalovirus (mcmv) induced myelosuppression by as101.infection with cytomegalovirus (cmv) continues to be one of the most common complications following allogeneic bone marrow transplantation. the gravest danger for the host occurs when the virus is reactivated as a result of immunosuppression. in this report we studied the effects of sublethal murine cytomegalovirus (mcmv) infection on the hemopoietic system including bone marrow (bm) cellularity, production of colony stimulating factor (csf) and interleukin-6 (il-6) and the development of granul ...19947721328
detection of murine cytomegalovirus (mcmv) dna in skin using the polymerase chain reaction (pcr).we used the polymerase chain reaction (pcr) and primers for the immediate early gene of murine cytomegalovirus (mcmv) to detect mcmv dna in skin harvested from mice during acute infection. mcmv dna was also detected in dna extracted from spleen and salivary gland of mcmv-infected mice, but not in the skin, salivary gland, or spleen of uninfected, seronegative mice. detection of mcmv dna in skin provides direct evidence that skin can serve as a vehicle for transmission of mcmv. this observation i ...19938412624
murine cytomegalovirus with a deletion of genes spanning hindiii-j and -i displays altered cell and tissue tropism.murine cytomegalovirus (mcmv) gene products dispensable for growth in cell culture are likely to have important functions within the infected host, influencing tissue tropism, dissemination, or immunological responses against the virus. to identify such genes, our strategy was to delete large regions of the mcmv genome likely to contain genes nonessential for virus replication in nih 3t3 cells. mutant virus rv7 contained a deletion of 7.7 kb spanning portions of mcmv hindiii-j and -i. this virus ...19968627652
selective cytotoxicity towards cytomegalovirus-infected cells by immunotoxins consisting of gelonin linked to anti-cytomegalovirus antibody.an immunotoxin specific for cells infected with human cytomegalovirus (hcmv) was constructed by attaching the ribosome-inactivating enzyme, gelonin, through a disulfide linkage to polyclonal human immunoglobulin (igg). in uninfected cells, there was no difference between [35s]methionine incorporation in untreated cultures and those treated with immunotoxin at 100 micrograms/ml. in hcmv-infected cells, there was a significant decrease in [35s]methionine incorporation in the immunotoxin-treated cu ...19958585763
spread of murine cytomegalovirus to inner ocular structures following disruption of the blood-retina barrier in immunosuppressed balb/c mice.the aims of this study were to determine whether disruption of the blood-retina barrier (brb) increases spread of murine cytomegalovirus (mcmv) to the eye after intraperitoneal inoculation and whether systemic immunosuppression influences the location of mcmv in the ocular compartment.19968603879
[ocular murine cytomegalovirus infection in immunocompromised hosts].cytomegalovirus (cmv) chorioretinitis is one of the commonest complications in immunocompromised hosts. however, the entire scope of ocular involvement during generalized cmv infection in immunocompromised hosts is yet to be elucidated. balb/c nude mice were inoculated intraperitoneally with smith strain of salivary gland passaged murine cytomegalovirus. eight days after infection, they were sacrificed and the pathological features of virus spread were studied by immunofluorescence method. subco ...19947976841
analysis of target organs for the latency of murine cytomegalovirus dna using specific pathogen free and germfree mice.cytomegalovirus (cmv) establishes a latent infection in its host; however, the organ sites of viral latency and its mechanism still remain to be fully clarified. to elucidate this issue, a latent infection with murine (m) cmv was attempted to induce in mice and the organ sites of the latent viral genome were examined for more than one year by a polymerase chain reaction (pcr). as a result, latent mcmv dna was detectable in both the lung and the spleen as late as 59 weeks after infection. the hea ...19957605198
investigation of murine cytomegalovirus latency and reactivation in mice using viral mutants and the polymerase chain reaction.studies with 6 ts mutants of mouse cytomegalovirus indicated that mutants tsm1, tsm2, tsm3, and tsm6, like wild-type (wt) virus, produced acute infection in mice, became latent, and were reactivated as infectious virus immunosuppression. using pcr, all five viruses expressed immediate-early (ie)-1, early (e)-1, and late (l, gb) genes during acute infection in all tissues examined (salivary glands, lung, spleen, liver, kidney, and heart). dna was present in most tissues during latent infection wi ...19968699162
exacerbation of collagen-induced arthritis in rats by rat cytomegalovirus is antigen-specific.collagen-induced arthritis (cia) is an experimentally induced and genetically controlled animal model of chronic joint inflammation. in rats, there are informative strain differences in susceptibility to cia. da rats (rt1avl) develop severe cia after immunization with bovine (bii), chick (cii), or homologous rat (rii) type ii collagens. in contrast, the mhc-congenic da. 1n(bn) and wf.1n(bn) rats (rt1n) are relatively resistant to cia and develop moderate cia in response to immunization with cii ...19947858103
cytomegalovirus hepatitis: characterization of the inflammatory infiltrate in resistant and susceptible mice.mice susceptible and resistant to murine cytomegalovirus (mcmv) were infected with this virus and livers were harvested after 2-231 days. cryostat sections were stained to visualize cells bearing cd4, cd8 or mac-1 antigens. mac-1+ cells were prevalent in inflammatory foci after 2 days. these cells persisted in susceptible balb/c and a/j mice, but disappeared from livers of resistant c57bl/6 and cba/cah mice by day 28. t cell inflammation peaked on days 7-11. this declined by day 56 in c57bl/6 an ...19947994901
il12 in acute viral infectious disease. 19958839166
trans-activation of the mouse cytomegalovirus immediate early gene enhancer by ras oncogenes.the ras gene family encodes 21k proteins that reside on the inner face of the plasma membrane and bind gtp and gdp with an equally high affinity. cotransfection of nih 3t3 cells with a mammalian expression vector containing a viral harvey-ras (v-ha-ras) cdna, together with a plasmid (pcmvcat) carrying the immediate early (ie) enhancer of the murine cytomegalovirus (mcmv) linked to the chloramphenicol acetyltransferase (cat) reporter gene strongly stimulated cat activity. basal levels of pcmvcat ...19948021597
down-regulation of major histocompatibility complex class i synthesis by murine cytomegalovirus early gene expression.murine cytomegalovirus (mcmv) infection of c57bl/6 (h-2b) mice prevents priming of antigen-specific helper and cytotoxic t lymphocytes (ctl) (j. s. slater, w. s. futch, v. j. cavanaugh, and a. e. campbell, virology 185:132-139, 1991). in vitro, mcmv infection alters presentation of antigens to antigen-specific, mhc class i-restricted ctl (a. e. campbell, j. s. slater, v. j. cavanaugh, and r. m. stenberg, j. virol. 66:3011-3017, 1992). this is accompanied by a significant decrease in surface expr ...19948107242
studies of the pathogenesis of wild-type virus and six temperature-sensitive mutants of mouse cytomegalovirus.a comparison of six temperature-sensitive (ts) mutants with the parental wild-type (wt) virus showed that, when 1-week-old balb/c mice were inoculated intraperitoneally with 300 pfu of mouse passaged virus, the viruses could be broadly categorized into two groups. two viruses (wt and tsm6) were lethal at this dose (10 and 2 ld50 respectively); animals died within 4-6 days of inoculation and the virus became generalized infecting heart, lung, liver, spleen, kidney, and salivary glands to high tit ...19947964641
identification, analysis, and evolutionary relationships of the putative murine cytomegalovirus homologs of the human cytomegalovirus ul82 (pp71) and ul83 (pp65) matrix phosphoproteins.we have identified three open reading frames (orfs) in murine cytomegalovirus (mcmv), designated m82, m83, and m84, which likely encode homologs of the human cytomegalovirus (hcmv) ul82 and ul83 matrix phosphoproteins. these orfs, in the hindiii c fragment of mcmv, are colinear with the ul82, ul83, and ul84 orfs of hcmv. m82 encodes a 598-amino-acid (aa) protein with homology to ul82, m83 encodes an 809-aa protein with homology to ul82 and ul83, and m84 encodes a 587-aa protein with homology to ...19968892916
antiviral activity of an immunomodulatory lipophilic desmuramyl dipeptide analog.bch-527, the lipophilic hydrochloride salt of octadecyl d-alanyl l-glutamine, was evaluated for efficacy against experimentally induced murine cytomegalovirus (mcmv), influenza a (h1n1) (iv-a), and punta toro virus (ptv) infections in mice. the compound was administered i.p. every other day for a total of 4 injections commencing 24 h previrus exposure. doses ranged from 12.5 to 200 mg/kg per injection in the various experiments. the mcmv infection was significantly inhibited in two experiments b ...19957605113
[serum stimulates the transcriptional activity of the enhancer of the immediate-early genes of the murine cytomegalovirus through p21 ras].the analysis of the mcmv ie enhancer revealed the presence of many putative binding sites for the transcription factors ap-1 and nfkb. previous studies suggested that such factors represent a final target for the metabolic cascade triggered by serum and growth factors. on these basis we wanted to verify if serum stimulates the transcriptional activity of the mcmv ie enhancer through p21ras and ap-1 and nfkb according to the actual model of transduction of the mitogenic signal. our data demonstra ...19948706976
peptides control the gain and loss of allele specificity by mutated mhc class i molecules.to analyze the molecular basis of mhc class i allele-restricted peptide recognition, a set of eight ld/lq mutants was constructed and tested for peptide recognition by allele-restricted and peptide-specific ctl. the mhc molecules h-2ld and h-2lq differ at six amino acid positions (95, 97, 107, 116, 155, 157) located within the alpha 2 domain of the molecule. both molecules present the lymphocytic choriomeningitis virus (lcmv) nucleoprotein-derived peptide rpqasgvym and the murine cytomegalovirus ...19957722309
characterization of early il-12, ifn-alphabeta, and tnf effects on antiviral state and nk cell responses during murine cytomegalovirus infection.murine cytomegalovirus (mcmv) infection of mice induces early cytokines. although certain of these can directly inhibit viral replication, they also can promote defense by activating nk cells. mcmv induces ifn-alphabeta-dependent nk cell cytotoxicity and il-12-dependent nk cell ifn-gamma production. studies were initiated to define cytokine-mediated nk and t cell-independent antiviral defense and specific cytokine-elicited nk cell responses during mcmv infections. ifn-alphabeta, tnf, il-12, and ...19968648121
[protein p53 inhibits the activity of the enhancer of the immediate-early genes of murine cytomegalovirus].the protein encoded by the tumor suppressor gene p53 can complex and functionally interact with cytomegalovirus proteins produced during the immediate-early phase of infection. the functions of these complex are unclear but there is some evidence to suggest that binding of p53 to these viral proteins may inactivate p53 functions. recent reports have shown that p53 is involved in regulation of transcription. in this study we have considered the possibility that p53 may regulate transcription of c ...19948706975
dna immunization confers protection against murine cytomegalovirus infection.the murine cytomegalovirus (mcmv) immediate-early gene 1 (ie1) encodes an 89-kda phosphoprotein (pp89) which plays a key role in protecting balb/c mice against the lethal effects of the mcmv infection. in this report, we have addressed the question of whether "naked dna" vaccination with a eukaryotic expression vector (pcdna-89) that contains the mcmv ie1 gene driven by a strong enhancer/promoter can confer protection. balb/c mice were immunized intradermally with pcdna-89 or with the plasmid ba ...19968892915
effect of ganciclovir on murine cytomegalovirus-induced reactivation of toxoplasma pneumonia.active cytomegalovirus (cmv) infection induces immunosuppression and predisposes to the development of life-threatening superinfections in immunocompromised patients. we have described a mouse model in which acute murine cmv (mcmv) infection reactivates previously dormant toxoplasma gondii infection, manifested as pneumonia. to determine whether therapy with ganciclovir might prevent mcmv-induced reactivation of t. gondii pneumonia, we administered ganciclovir to mice starting 1 day before to 2 ...19938228576
pathogenesis of ocular cytomegalovirus infection in the immunocompromised host.balb/c nude and c.b-17 scid mice were inoculated with salivary gland passaged cytomegalovirus (sg-mcmv) intraperitoneally. dissemination of the virus in the systemic and ocular tissues was studied by the direct immunofluorescence test, and the virus growth in each tissue was titrated in mouse embryonic fibroblasts. the mode of viral spread was assessed by inhibiting macrophage function by silica and administering polyclonal murine anti-mcmv antibody in the circulation. the virus first reached th ...19958636704
assessment of antigenicity and genetic variation of glycoprotein b of murine cytomegalovirus.an analysis of linear antibody-binding sites of the glycoprotein b (gb) molecule of murine cytomegalovirus (mcmv) and of genetic variation within these regions was performed. to achieve this, a series of overlapping fragments spanning the entire coding sequence of the gb gene of the k181 strain of mcmv was expressed in e. coli as fusion proteins with glutathione s-transferase (gst) using the pgex expression system. four antibody-binding regions were mapped to locations spanning amino acid residu ...19968558128
immunosuppression induces transcription of murine cytomegalovirus glycoprotein h in the eye and at non-ocular sites.in these studies, dna pcr was used to identify sites of murine cytomegalovirus (mcmv) latency after inoculation of virus into the supraciliary space of the eye. reverse transcription (rt) pcr for an immediate early gene and a late gene was used to identify putative sites of virus reactivation after methylprednisolone (steroid)-induced immunosuppression. ten weeks after inoculation of 5 x 10(2) pfu of mcmv, balb/c mice were immunosuppressed by intramuscular injection of steroid. control mice were ...19968645084
selective cytotoxicity of ricin a chain immunotoxins towards murine cytomegalovirus-infected cells.immunotoxins were constructed by linking immunoglobulins specific for murine cytomegalovirus (mcmv) to deglycosylated ricin a chain. toxicities toward mcmv-infected and uninfected cells were determined by measuring the inhibition of protein synthesis following a 48-h exposure to immunotoxins commencing 24 h after infection. the 50% inhibitory concentrations ranged from 0.4 to 4 micrograms/ml for infected cells and from 22 to 120 micrograms/ml for uninfected cells. selectivity indices ranged from ...19968834901
an absolute and restricted requirement for il-12 in natural killer cell ifn-gamma production and antiviral defense. studies of natural killer and t cell responses in contrasting viral infections.il-12 is a potent induce of ifn-gamma and is associated with a wide variety of immunoregulatory activities. using murine cmv (mcmv) and lymphocytic choriomeningitis virus (lcmv) models of acute viral infection, we show here that il-12 is integrally involved in certain aspects of antiviral immunity. experiments evaluating the production and function of il-12 demonstrated the induction of biologically active factor early during smith strain mcmv, but not armstrong strain lcmv, infection. the mcmv- ...19968557990
identification and characterization of a g protein-coupled receptor homolog encoded by murine cytomegalovirus.this report describes the identification of a murine cytomegalovirus (mcmv) g protein-coupled receptor (gcr) homolog. this open reading frame (m33) is most closely related to, and collinear with, human cytomegalovirus ul33, and homologs are also present in human herpesvirus 6 and 7 (u12 for both viruses). conserved counterparts in the sequenced alpha- or gammaherpesviruses have not been identified to date, suggesting that these genes encode proteins which are important for the biological charact ...19978995678
analysis of the complete dna sequence of murine cytomegalovirus.the complete dna sequence of the smith strain of murine cytomegalovirus (mcmv) was determined from virion dna by using a whole-genome shotgun approach. the genome has an overall g+c content of 58.7%, consists of 230,278 bp, and is arranged as a single unique sequence with short (31-bp) terminal direct repeats and several short internal repeats. significant similarity to the genome of the sequenced human cytomegalovirus (hcmv) strain ad169 is evident, particularly for 78 open reading frames encod ...19968971012
distinct organ-dependent mechanisms for the control of murine cytomegalovirus infection by natural killer cells.antiviral mechanisms by which natural killer (nk) cells control murine cytomegalovirus (mcmv) infection in the spleens and livers of c57bl/6 mice were measured, revealing different mechanisms of control in different organs. three days postinfection, mcmv titers in the spleens of perforin 0/0 mice were higher than in those of perforin +/+ mice, but no elevation of liver titers was found in perforin 0/0 mice. nk cell depletion in mcmv-infected perforin 0/0 mice resulted only in an increase in live ...19978985346
late expression of a beta chemokine homolog by murine cytomegalovirus.a gene (hj1) present in murine cytomegalovirus (mcmv) encodes an open reading frame (orf) whose predicted amino acid sequence shows homology to the beta (or c-c) class of chemotactic cytokines known as chemokines. the region of homology is located in the carboxyl-terminal portion of the 116-amino-acid orf. a 0.9-kb rna transcript corresponding to the hj1 gene is expressed in mcmv-infected fibroblasts and macrophages as a member of the late kinetic class of virally encoded transcripts. a transcri ...19978995698
combination of antiviral immunotoxin and ganciclovir or cidofovir for the treatment of murine cytomegalovirus infections.the effects of two anti-murine cytomegalovirus (mcmv) immunotoxins used in combination with ganciclovir (gcv) or cidofovir (hpmpc) against mcmv were determined in vitro and in mice. the inhibitors were added to cell cultures 24 or 48 h after mcmv adsorption so as to not affect the initial infection rate. the immunotoxins (0.63, 1.25 and 2.5 micrograms/ml) combined with gcv (1.25, 2.5 and 5 microm) or hpmpc (0.03, 0.06 and 0.12 microm) caused synergistic inhibition of virus yield in c127i cells a ...19968955511
impact of prophylactic ganciclovir on bronchoalveolar lavage lymphocyte numbers and phenotypes in murine cytomegalovirus-induced reactivation of toxoplasma pneumonia.in a mouse model of cytomegalovirus (cmv)-induced immunosuppression, murine cmv (mcmv) infection results in reactivation of toxoplasma pneumonia, and prophylactic but not delayed administration of ganciclovir attenuates the severity of this pneumonia. we now report that the protection observed with ganciclovir is associated with blunting of the alterations in bronchoalveolar lavage (bal) lymphocyte numbers and phenotypes observed in untreated mice. specifically, prophylactic ganciclovir prevents ...19968833887
further studies of 31 temperature-sensitive mutants of mouse cytomegalovirus: thermal stability, replication and analysis of temperature-sensitive functions by temperature shift.a study of 31 temperature-sensitive mutants of mouse cytomegalovirus has indicated that two mutants (tsm1, tsm31) may be defective in immediate-early/early functions, two (tsm2, tsm3) may be defective in early functions and six (tsm9, tsm18, tsm22, tsm23, tsm28, tsm30) may be defective in early/late functions while the remainder are late function-defective mutants as determined by temperature-shift experiments. three mutants (tsm1, tsm2, tsm3) were more thermostable than wild-type virus while th ...19938288108
treatment of murine cytomegalovirus salivary-gland infection by combined therapy with ganciclovir and thymic humoral factor gamma 2.an optimal therapeutic regimen against primary cmv salivary-gland infection has not yet been developed. we used a murine cmv (mcmv) model system to assess the ability of combined thymic humoral factor thf-gamma 2 immunotherapy and ganciclovir (gcv) antiviral chemotherapy to eliminate detectable viral dna from salivary glands of infected animals. mice in different experimental groups were inoculated intraperitoneally with mcmv, treated, and then sacrificed either 2 weeks or 3 months later. to amp ...19968955853
adrenalitis and the adrenocortical response of resistant and susceptible mice to acute murine cytomegalovirus infection.murine cytomegalovirus (mcmv) induces adrenalitis in balb/c mice but does not compromise adrenal function, assessed by levels of circulating adrenocorticotropic hormone (acth) and by the response to challenge with synthetic acth. levels of corticosterone increased 2 days after infection in mice of this strain, consistent with previously established interactions between mediators of acute inflammation and activation of the hypothalmus-pituitary-adrenal axis. moreover, an adrenocortical response w ...19968889445
effect of host genotype in determining the relative roles of natural killer cells and t cells in mediating protection against murine cytomegalovirus infection.the influence of host genotype on the relative importance of t cell subsets and natural killer (nk) cells in controlling murine cytomegalovirus (mcmv) replication has been investigated. genetically susceptible balb/c and a/j, moderately resistant c57bl/10, and resistant cba/cah mouse strains were treated with monoclonal antibodies (mab) to the cd4 and cd8 markers and the extent of mcmv replication in major target tissues was determined. both mouse strain-specific and tissue-specific effects were ...19968887497
effect of natural sequence variation at the h-2ld-restricted cd8+ t cell epitope of the murine cytomegalovirus ie1-encoded pp89 on t cell recognition.the amino acid sequence yphfmptnl of pp89, the ie1-encoded product of murine cytomegalovirus (mcmv; smith strain), constitutes an immunodominant t cell epitope recognized in association with h-2ld. nucleotide sequencing of mcmv isolates derived from wild mice identified variation between amino acids 147-192 of pp89 in 19 of 27 isolates, including the region encompassing the ctl epitope (amino acid residues 168-176). four groups of isolates with naturally occurring variant sequences for the ctl e ...19968887498
potent anti-murine cytomegalovirus activity and reduced nephrotoxicity of ganciclovir cyclic phosphonate.ganciclovir cyclic phosphonate (sr3775) is a derivative of the r enantiomer (sr3773) of ganciclovir phosphonate (9-[((+/-)-1-hydroxymethyl-3-phosphono)propyloxymethyl]guanine), both of which are potent inhibitors of human ctyomegalovirus and murine cytomegalovirus (mcmv). against wild-type and four drug-resistant strains of mcmv, sr3773 was 2.3- to 3-fold more potent than sr3775. sr3775 was about half as active as sr3773 against mcmv infections in severe combined immunodeficient mice. however, w ...19968843317
late phase inhibition of murine cytomegalovirus replication by synergistic action of interferon-gamma and tumour necrosis factor.we have shown previously that the antiviral function of cd4+ t lymphocytes against murine cytomegalovirus (mcmv) is associated with the release of interferon-gamma (ifn-gamma). we now demonstrate that ifn-gamma and tumour necrosis factor alpha (tnf-alpha) display synergism in their antiviral activity. as little as 2 ng/ml of ifn-gamma and tnf-alpha reduced the virus yield by about three orders of magnitude. there was no effect on immediate early (ie) and early (e) gene expression as far as the c ...19948113718
inhibition by iota-carrageenan of the spread of murine cytomegalovirus from the peritoneal cavity to the blood plasma.the mechanism of iota-carrageenan (i-car)-induced protection against murine cytomegalovirus (mcmv) infection of mice was analysed. the virus titres in the target organs on the fourth day correlated with that in the plasma at 1 h after intraperitoneal inoculation of mcmv, irrespective of i-car treatment. pretreatment of mice with i-car induced infiltration of polymorphonuclear neutrophils into the peritoneal cavity and inhibition of viral spread from the peritoneal cavity to the plasma. although ...19948113719
expression of the murine cytomegalovirus glycoprotein h by recombinant vaccinia virus.the sequence of the gene encoding glycoprotein h (gh) of murine cytomegalovirus (mcmv) strain smith was determined and compared with the sequence of the gh of mcmv strain k181. transcriptional analysis showed that gh is encoded by a large mrna of 5.0 kb, which is synthesized late in infection. a recombinant vaccinia virus expressing the mcmv gh open reading frame was constructed (vac-gh). anti-mcmv serum precipitated a protein of 87k from vac-gh-infected cells. reactivity with a monoclonal antib ...19948113726
camp response element of murine cytomegalovirus immediate early gene enhancer is transactivated by ras oncogene products.products of ras oncogenes strongly stimulate the activity of the reporter gene, chloramphenicol acetyltransferase (cat), driven by a 1.2 kb fragment of the murine cytomegalovirus (mcmv) immediate early (ie) gene enhancer (pcmvcat). to define the role of proteins binding to the unique camp response element (cre) present in the ie enhancer, nih 3t3 cells were cotransfected with praszip6 plasmid, a mammalian expression vector containing a v-ha-ras cdna, together with p(delta)acmvcat (pcmvcat withou ...19959049320
suppression of high mobility group protein t160 expression impairs mouse cytomegalovirus replication.the high mobility group (hmg-1) box proteins bind both non-b-dna conformations and specific nucleotide sequences. they have been implicated in a wide variety of cellular functions involving dna, such as transcription, replication and recombination. to determine whether hmg-1 box protein t160 plays a role in virus replication, we employed an antisense strategy to inhibit its expression in nih 3t3 cells. the two t160 clones that expressed levels of t160 50% lower than those expressed by clones tra ...19979049420
a mouse cytomegalovirus glycoprotein, gp34, forms a complex with folded class i mhc molecules in the er which is not retained but is transported to the cell surface.murine cytomegalovirus (mcmv) interferes with antigen presentation by means of retaining major histocompatibility complex (mhc) class i molecules in the endoplasmic reticulum (er). here we identify and characterize an mcmv-encoded glycoprotein, gp34, which tightly associates with properly conformed mhc class i molecules in the er. gp34 is synthesized in large quantities during mcmv infection and it leaves the er only in association with mhc class i complexes. many but not all class i molecules a ...19979049298
murine cytomegalovirus dna in peripheral blood of latently infected mice is detectable only in monocytes and polymorphonuclear leukocytes.cytomegalovirus (cmv), as do other herpesviruses, establishes a lifelong latent infection in its natural host. while in immunologically intact hosts most cmv infections are subclinical, clinical disease follows severe immunosuppression and immunodeficiency. in these situations cmv may produce serious life-threatening disease, and virus reactivated from the latent state is often responsible. essential to understanding this virus and its pathogenesis is the need to define particular tissue and cel ...19968806553
rat cytomegalovirus has a unique immediate early gene enhancer.the immediate early (ie) enhancer/promoter regions of human cytomegalovirus (hcmv), simian cytomegalovirus (scmv), and murine cytomegalovirus (mcmv) share the following characteristics: (1) they demonstrate high-level transcriptional properties, (2) multiple repetitive elements are found throughout the enhancer region, and (3) consensus binding sites for cellular transcription factors are frequently located within the repetitive elements. here we characterize the enhancer/promoter region of the ...19968806515
concurrent mcmv infection augments donor antihost-specific activity and alters clinical outcome following experimental allogenic bone marrow transplantation.the present studies were undertaken to examine whether concurrent mcmv infection during allogeneic bone marrow transplantation (bmt) could alter the developing donor-host immune interactions and affect the overall outcome of the transplant. in order to determine the effect of mcmv on antihost activity arising following an allogeneic bmt, specific donor antihost cytotoxicity was examined. the results demonstrated that concurrent virus infection in mice receiving a bmt from donors either h2-matche ...19968623149
latency versus persistence or intermittent recurrences: evidence for a latent state of murine cytomegalovirus in the lungs.the state of cytomegalovirus (cmv) after the resolution of acute infection is an unsolved problem in cmv research. while the term "latency" is in general use to indicate the maintenance of the viral genome, a formal exclusion of low-level persistent productive infection depends on the sensitivity of the assay for detecting infectious virus. we have improved the method for detecting infectivity by combining centrifugal infection of permissive indicator cells in culture, expansion to an infectious ...19979060657
latent murine cytomegalovirus infection in macrophages.in this study we show that macrophages (mphi) are latently infected with murine cytomegalovirus (mcmv). after clearance of acute mcmv infection, the predominant form of chronic infection in balb mice is latency rather than persistence. peritoneal exudate cells (pecs) from latently infected balb mice (3-9 months postinfection) contained mcmv genome and reactivatable virus. adherent cells from both resident and thioglycollate-elicited pecs carried more mcmv dna (measured by pcr) than nonadherent c ...19979007070
murine cytomegalovirus inactivated by sodium periodate is innocuous and immunogenic in mice and protects them against death and infection.sodium periodate (10 mm, 4 degrees c) inactivated murine cytomegalovirus (mcmv) very rapidly (loss of 2 to 3 log of viral infectivity per minute). periodate-treated mcmv (pi-mcmv) was shown to be innocuous in mice, as determined by the inability of the virus to replicate. pi-mcmv induced a strong humoral immune response, with a high level of neutralizing antibodies. mice immunized with pi-mcmv were protected against death and infection, when a lethal challenge with the virulent virus was adminis ...19969032900
efficacy of bms-180194 against experimental cytomegalovirus infections in immunocompromised mice.a new antiviral nucleoside, bms-180194 [1r-(1 alpha, 2 beta, 3 alpha)]- 2-amino-9[2,3-bis(hydroxymethyl)cyclobutyl]-1,9dihydro-6h-purin-6- one, is a broad spectrum antiviral agent. the antiviral effectiveness of bms-180194 against murine cytomegalovirus (mcmv) infection in immunocompromised c57bl/6 mice was investigated and was compared to that of ganciclovir (gcv). lp-bm5 murine retrovirus complex-induced immunocompromised c57bl/6 mice were challenged with mcmv then treated intraperitoneally or ...19968739602
antiviral activity of 9-[[(ethoxyhydroxyphosphinyl)-methoxy]methoxy] guanine against cytomegalovirus and herpes simplex virus.an isosteric analog of 9-[2-(phosphonomethoxy)ethyl]guanine (pmeg), 9-[[(ethoxyhydroxyphosphinyl)methoxy]methoxy]guanine (ski 1008), was evaluated for its in vitro antiviral activity against herpes simplex virus type 1 (hsv-1) and type 2 (hsv-2), murine cytomegalovirus (mcmv), and human cytomegalovirus (hcmv), and its in vivo antiviral efficacy against mcmv in mice. the in vitro anti-hsv activity of ski 1008 was much lower than that of acyclovir, even though ski 1008 showed similar antiviral act ...19958629816
the location and sequence composition of the murine cytomegalovirus replicator (orilyt).dna replication during human or simian cytomegalovirus (cmv) infection has been shown to be under control of a replicator region referred to as orilyt. the murine cmv orilyt has been mapped to a region of the genome located upstream of the gene encoding the herpesvirus-conserved single-stranded dna binding protein, analogous to human and simian cmv orilyts. a minimal orilyt of approximately 1.7 kbp has been identified using a transient replication system. like occurs with human and simian cmv co ...19979143291
the in vivo expression patterns of individual type i interferon genes in murine cytomegalovirus infections.type i interferon (ifn) family has more than 10 structurally related subtypes of alpha ifn (ifna) genes and a single beta ifn (ifnb) gene. this study examined the expression of muifna1, a4, a5, a6, a9 and muifnb mrnas in the livers and spleens of mcmv-infected mice at 2, 4 and 6 h post infection. the three strains of inbred mice studied were c57bl/6, b6.c-h-28c and balb/c. b6.c-h-28c strain is a congenic strain of c57bl/6 genomic background. detection of the specific mrnas was by an established ...19979107382
effect of a retroviral immunodeficiency syndrome on murine cytomegalovirus-induced hepatitis.we have studied the effects of lp-bm5 mulv-induced murine acquired immunodeficiency syndrome (maids) on concomitant murine cytomegalovirus (mcmv) infection in the livers of c57bl mice. a delayed inflammatory response in livers of mice with maids (m+) on day 4 was associated with impaired clearance of mcmv-infected cells 6 days after infection. this correlated with increased levels of inflammation and serum alanine transaminase. the latter reflects enhanced hepatic necrosis, which was evident his ...19979060844
characterization of early cytokine responses and an interleukin (il)-6-dependent pathway of endogenous glucocorticoid induction during murine cytomegalovirus infection.early infection with murine cytomegalovirus (mcmv) induces circulating levels of interleukin (il)-12, interferon (ifn)-gamma, and tumor necrosis factor (tnf). studies presented here further characterize these responses by defining kinetics and extending evaluation to include il-1, il-6, and glucocorticoids. il-12 p40, ifn-gamma, tnf, il-1alpha, and il-6 were shown to be increased, but il-1beta was undetectable, in serum of mcmv-infected mice. the il-12 p40, ifn-gamma, tnf, and il-6 responses wer ...19979104805
novel therapeutic strategies against cytomegalovirus infection.murine cmv (mcmv) presents a model for the study of the role of the immune system in the pathogenesis of human cmv (hcmv) infection. mcmv causes t cell immune impairment in the infected mice, manifested by suppressed responses to t cell mitogens and a profound reduction of con a induced il-2 production. thymic humoral factor (thf-gamma 2) is an octapeptide which was first isolated from calf thymus, characterized and chemically synthesized. this peptide has been shown to have immunoregulatory eff ...19958933819
mechanisms for virus-induced liver disease: tumor necrosis factor-mediated pathology independent of natural killer and t cells during murine cytomegalovirus infection.the contribution of endogenous nk cells and cytokines to virus-induced liver pathology was evaluated during murine cytomegalovirus infections of mice. in immunocompetent c57bl/6 mice, the virus induced a self-limited liver disease characterized by hepatitis, with focal inflammation, and large grossly visible subcapsular necrotic foci. the inflammatory foci were most numerous and contained the greatest number of cells 3 days after infection; they colocalized with areas of viral antigen expression ...19979371583
the cmv1 host resistance locus is closely linked to the ly49 multigene family within the natural killer cell gene complex on mouse chromosome 6.natural killer (nk) cells play important roles in controlling tumor cells and against a range of infectious organisms. recent studies of mouse nk cell surface receptors, which may be involved in the specificity of nk cells, have shown that many of these molecules are encoded by the ly49 and ly55 (nkrp1) multigene families that map to distal mouse chromosome 6. also mapping to this nk cell gene complex (nkc) is the resistance locus, cmv1, which is involved in genetically determined resistance to ...19979169139
systemic cytokine immunotherapy for experimental cytomegalovirus retinitis in mice with retrovirus-induced immunodeficiency.to evaluate and compare the in vivo administration of interleukin-2 (il-2) or interleukin-12 (il-12) in the immunotherapy of necrotizing retinitis caused by murine cytomegalovirus (mcmv) in mice with a retrovirus-induced immunodeficiency syndrome (maids).19979191604
lactoferrin-mediated protection of the host from murine cytomegalovirus infection by a t-cell-dependent augmentation of natural killer cell activity.the administration of bovine lactoferrin (lf) with 1 mg/g body weight before the murine cytomegalovirus (mcmv) infection completely protected the balb/c mice from death due to the infection. in these lf-treated mice, a significant increase in the activity was found in the nk cells but not in the cytolytic t lymphocytes which recognized an mcmv-derived peptide. moreover, the elimination of the nk cell activity by an injection with anti-asialo gm1 antibody abrogated such augmented resistance, thus ...19968920822
murine cytomegalovirus replication in the lungs of athymic balb/c nude mice.murine cytomegalovirus (mcmv) infection in the lungs of t cell-deficient athymic balb/c (nu/ nu) mice and their immunocompetent heterozygous (nu/+) littermates was examined. following intranasal inoculation, mcmv replicated in the lungs of both nu/nu and nu/+ mice, but virus titers were significantly higher in t cell-deficient mice. after subcutaneous inoculation, virus disseminated to lung tissue of athymic mice, leading to progressive mcmv replication in lungs that was not seen in the immunoco ...19979203651
nitric oxide mediates murine cytomegalovirus-associated pneumonitis in lungs that are free of the virus.4 wk after intraperitoneal inoculation of 0.2 ld50 (50% lethal dose) of murine cytomegalovirus (mcmv) in adult balb/c mice, mcmv remained detectable in the salivary glands, but not in the lungs or other organs. when the t cells of these mice were activated in vivo by a single injection of anti-cd3 monoclonal antibody, interstitial pneumonitis was induced in the lungs that were free of the virus with an excessive production of the cytokines. in the lungs of such mice persistently infected with mc ...19979312183
differential expression of the immediate-early and early antigens in neuronal and glial cells of developing mouse brains infected with murine cytomegalovirus.brain disorders induced by congenital cytomegalovirus (cmv) infection may appear at a later time after birth as a consequence of persistent infection and/or the activation of a latent infection of the neural cells. we have analyzed the infection dynamics of the neural cells in the neonatal mouse brains infected with murine cmv (mcmv) in the late stage of gestation. first we prepared a rat monoclonal antibody to the major immediate-early (ie)-89k antigen and then used the antibody for comparison ...19979358759
effect of immunosuppression on balb/c mice infected with murine herpesvirus.balb/c mice were infected with murine herpesvirus (mhv-72) and subjected to immunosuppression (is) with the antibiotic fk506 either during the acute or chronic phase of infection. attempts to detect virus in various organs of immunosuppressed and non-immunosuppressed mice at different time interval were made. in the mice immunosuppressed on days 3-23 p.i. of the acute phase of infection virus was detected in various tested organs and tissues at 2.0 times higher rate than those of control mice. a ...19968886097
recombinant cytomegaloviruses for study of replication and pathogenesis.systematic mutagenesis of large viral genomes such as those of the cytomegaloviruses requires strategies for identifying relevant functions as well as for detailed analysis of particular genes. a number of genetic markers that have been developed in other biological systems have been useful for insertion mutagenesis in these viruses. thus far, 57 of the over 227 genes carried by wild-type human cytomegalovirus have been found to be dispensable for growth in cultured cells. because of the limitat ...19969130042
antibody alone does not prevent experimental cytomegalovirus retinitis in mice with retrovirus-induced immunodeficiency (maids).passive-transfer studies were performed to assess the ability of antibody alone to reduce the frequency and/or severity of necrotizing retinitis caused by murine cytomegalovirus (mcmv) in c57bl/6 mice with retrovirus-induced immunodeficiency syndrome (maids). initial experiments showed a gradual decline in the ability of mice to initiate humoral immunity during the evolution of maids so that neither mcmv-specific igm nor igg could be detected during late-stage maids. passively administered hyper ...19979380340
early murine cytomegalovirus (mcmv) infection induces liver natural killer (nk) cell inflammation and protection through macrophage inflammatory protein 1alpha (mip-1alpha)-dependent pathways.natural killer (nk) cells mediate defense against early murine cytomegalovirus (mcmv) infections in liver. the chemokine, macrophage inflammatory protein 1alpha (mip-1alpha), can promote inflammatory responses. our studies evaluated contributions of nk cells to early mcmv-induced liver inflammation and mip-1alpha requirements for inflammation and delivery of antiviral defenses. nk cells were shown to be responsible for focal inflammation, and to be induced to migrate at high levels, in mcmv-infe ...19989419206
a mouse cytomegalovirus glycoprotein retains mhc class i complexes in the ergic/cis-golgi compartments.the principle by which mouse cytomegalovirus blocks antigen presentation in the mhc class i pathway was investigated. the responsible gene m152, encoding a type i transmembrane glycoprotein of 40 kda, is a member of a gene family located in the right-hand terminal region of the 230 kb virus genome. expression of m152 in murine and human cells arrested the export of mouse class i complexes from the er-golgi intermediate compartment/cis-golgi compartment and inhibited lysis by cytotoxic t cells. t ...19979052837
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