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efficiency of different viral promoters in directing gene expression in mammalian cells: effect of 3'-untranslated sequences.we compared (i) the enhancer/promoter (mcmv promoter) from the murine cytomegalovirus (cmv) major immediate early gene,(ii) the enhancer/promoter from human cmv major immediate early gene, containing a short promoter (h1cmv) or a long stretch of 5' untranslated region (utr) from the gene promoter (h2cmv) and (iii) the simian virus 40 (sv40) enhancer/early region promoter (sv2) for their ability to direct foreign gene expression in transiently transfected mammalian cell lines. two series of recom ...19968654943
hepatitis b virus core particles as epitope carriers.hbv core (hbc) particle is one of the most intensively studied particulate carriers for the insertion of foreign peptide sequences. recombinant hbc protein expressed from the cloned gene undergoes the correct folding in a large variety of bacterial, yeast, insect and mammalian cells. unique assembly properties and shape of 30/34-nm hbc particles allow substantial insertions into their primary structure without loss of their capsid-forming ability. n- and c-terminal regions, as well as the immuno ...19958666525
function and regulation of natural killer (nk) cells during viral infections: characterization of responses in vivoalthough in vitro systems have provided important information about the composition and nature of various immune responses, understanding physiologically relevant function and regulation requires evaluating in vivo conditions. two different models of acute viral infections have made possible the characterization of a variety of responses to these agents, including natural killer (nk) cell activation and regulation during infection; these are mouse infections with lymphocytic choriomeningitis vir ...19968812691
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
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
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
prophylactic treatment of cytomegalovirus infection with traditional herbs.hot water extracts of four traditional herbs, geum japonicum, syzygium aromaticum, terminalia chebula and rhus javanica, which have been shown to have anti-herpes simplex virus (hsv) activity in vivo, were examined for anti-cytomegalovirus (cmv) activity in vitro and in vivo in this study. they inhibited replication of human cmv and murine cmv (mcmv) in vitro. these anti-cmv activities in vivo were examined in an mcmv infection model using immunosuppressed mice. mice were subcutaneously treated ...19968891165
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
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
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
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
interferon-alpha/beta inhibition of interleukin 12 and interferon-gamma production in vitro and endogenously during viral infection.interferon (ifn)-alpha/beta-mediated negative regulation of interleukin 12 (il-12) and ifn-gamma proteins is reported here. both ifn-alpha and ifn-beta inhibited fixed staphylococcus aureus cowan strain induction of il-12 and ifn-gamma production by mouse splenic leukocytes in culture. extended studies with ifn-alpha demonstrated that inhibition was at the level of biologically active il-12 p70. effects were selective, as induction of tumor necrosis factor was unaffected and induction of il-6 wa ...19979012836
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
adoptive transfer of murine cytomegalovirus-immune lymph node cells prevents retinitis in t-cell-depleted mice.the purpose of this study was to determine whether adoptive transfer of murine cytomegalovirus (mcmv)-immune lymph node cells prevents retinitis in immunosuppressed mice.19979040462
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
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
ifn-gamma is a prerequisite for optimal antigen processing of viral peptides in vivo.the immediate early protein pp89 of mouse cmv is processed into the nonapeptide yphfmptnl, which is presented to cd8+ t lymphocytes by the h-2 ld molecule. the tissue distribution of this peptide was determined during the course of mouse cmv infection. in tissues, there was no general correlation between peptide processing and infectious virus productivity. immunosuppression by sublethal irradiation resulted in enhanced mcmv replication but did not increase the peptide yield and drastically redu ...19979120287
down-regulation of mhc class i synthesis by murine cytomegalovirus occurs in immortalized but not primary fibroblasts.murine cytomegalovirus downregulates expression of mhc class i molecules required for recognition of virus-specific cd8+ ctl, effector cells which mediate clearance of virus from the host. we previously identified two mechanisms of mhc class i downregulation in mcmv-infected immortalized fibroblasts: a defect in transport of the class i molecules from the endoplasmic reticulum to the cell surface, and a significant inhibition in class i heavy chain synthesis. we now report that these two mechani ...19979123864
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
disordered migration and loss of virus-infected neuronal cells in developing mouse brains infected with murine cytomegalovirus.microcephaly is the most prominent symptom of the developmental brain abnormalities induced by congenital cytomegalovirus (cmv) infection. to investigate the effect of cmv infection on neuronal migration in developing brains, mouse embryos on one side of uteri received, on day 15.5 of gestation (e15.5), an injection of murine cmv (mcmv) into the cerebral ventricles, and the embryos on the other side of the uteri were injected with minimum essential medium (mem). labeling with 5-bromo-2-deoxyurid ...19979194893
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
metabolism of ganciclovir and cidofovir in cells infected with drug-resistant and wild-type strains of murine cytomegalovirus.murine cytomegalovirus (mcmv) has been used extensively as an animal model for human cytomegalovirus (hcmv). understanding drug resistance and its treatment in mcmv may lead to more effective treatments of hcmv disease. most ganciclovir-resistant hcmv clinical isolates exhibit a decreased capacity to induce ganciclovir phosphorylation (to its biologically active form) in infected cells. using an mcmv strain resistant to both ganciclovir and cidofovir, the intracellular metabolism of these drugs ...19979217245
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
low-dose oral type i interferons reduce early virus replication of murine cytomegalovirus in vivo.immunity to viral infections involves both innate and antigen-specific immune responses. the antiviral properties of interferons (ifns) are part of the innate immune response. low doses of type i ifns (ifn-alpha and ifn-beta) administered daily (10 iu per mouse) by the oral route significantly reduced the early replication of murine cytomegalovirus (mcmv) in both the spleen and liver of mcmv-infected susceptible balb/c mice. significant inhibition of virus replication was observed for two differ ...19979355964
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
augmentation of natural killer cell activity induced by cytomegalovirus infection in mice treated with fk506.comparable rates of patient and graft survival after fk506 and cyclosporine treatments have been reported in the prevention of liver allograft rejection. on this basis, we examined the effect of fk506 on pathogenesis of cytomegalovirus (cmv) infection in mice. fk506 induced apparent immunosuppression in mice which could be monitored by the level of antibody production. the effective dose of trinitrophenyl-keyhole limpet hemocyanin (tnp-klh) for 50% reduction in antibody production was 0.9 mg/kg. ...19979391652
cellular localization of latent murine cytomegalovirus.herpesviruses typically establish latent infection in their hosts. the cell(s) responsible for harboring latent virus, in most cases, is not known. using immunofluorescence and pcr-in situ hybridization (pish), a technique which combines the sensitivity of pcr with the localization and specificity of in situ hybridization, we provide the first direct evidence that endothelial cells are a major site of murine cytomegalovirus (mcmv) dna in latently infected animals. these findings are consistent w ...19989420204
mucosal and parenteral vaccination against acute and latent murine cytomegalovirus (mcmv) infection by using an attenuated mcmv mutant.we used a live attenuated murine cytomegalovirus (mcmv) mutant to analyze mechanisms of vaccination against acute and latent cmv infection. we selected mcmv mutant rv7 as a vaccine candidate since this virus grows well in tissue culture but is profoundly attenuated for growth in normal and severe combined immunodeficient (scid) mice (v. j. cavanaugh et al., j. virol. 70:1365-1374, 1996). balb/c mice were immunized twice (0 and 14 days) subcutaneously (s.c.) with tissue culture-passaged rv7 and t ...19989420244
(z)- and (e)-2-((hydroxymethyl)cyclopropylidene)methyladenine and -guanine. new nucleoside analogues with a broad-spectrum antiviral activity.new nucleoside analogues 14-17 based on a methylenecyclopropane structure were synthesized and evaluated for antiviral activity. reaction of 2,3-dibromopropene (19) with adenine (18) led to bromoalkene 20, which was benzoylated to give n6,n6-dibenzoyl derivative 23. attempts to convert 20 or 23 to bromocyclopropanes 21 and 22 by reaction with ethyl diazoacetate catalyzed by rh2(oac)4 were futile. by contrast, 2,3-dibromopropene (19) afforded smoothly (e)- and (z)-dibromocyclopropane carboxylic e ...19989438017
virus attenuation after deletion of the cytomegalovirus fc receptor gene is not due to antibody control.the murine cytomegalovirus (mcmv) fcr-1 gene codes for a glycoprotein located at the surface of infected cells which strongly binds the fc fragment of murine immunoglobulin g. to determine the biological significance of the fcr-1 gene during viral infection, we constructed mcmv fcr-1 deletion mutants and revertants. the fcr-1 gene was disrupted by insertion of the escherichia coli lacz gene. in another mutant, the marker gene was also deleted, by recombinase cre. as expected for its hypothetical ...19989445038
[cytomegalovirus infection and its possible treatment with herbal medicines].medicinal herbs, geum japonicum, syzygium aromaticum, terminalia chebula, and rhus javanica, with anti-herpes simplex virus therapeutic activity, inhibited replication of human cytomegalovirus(cmv) and murine cmv(mcmv) in vitro. these anti-cmv activities were examined in an mcmv infection model using immunosuppressed mice. geum japonicum, syzygium aromaticum, and terminalia chebula significantly suppressed mcmv yields in lungs of treated mice compared with water treatment. efficacy of oral treat ...19989465682
murine cytomegalovirus infection inhibits ifn gamma-induced mhc class ii expression on macrophages: the role of type i interferon.macrophage (m phi) activation, as measured by cell surface expression of mhc class ii, was examined during infection of immunocompetent and immunocompromised mice with murine cytomegalovirus (mcmv). intraperitoneal infection of cb17 scid mice with 10(6) pfu of mcmv elicited a large population of m phi which expressed low levels of mhc class ii. this was surprising since infection of scid mice with lower doses (e.g., 10(4) pfu) of mcmv elicits m phi expressing high levels of mhc class ii (m. t. h ...19989499808
maize chlorotic mottle machlomovirus and wheat streak mosaic rymovirus concentrations increase in the synergistic disease corn lethal necrosis.corn lethal necrosis (cln) is caused by the synergistic interaction between maize chlorotic mottle machlomovirus (mcmv) and any potyvirus which infects cereals. interactions between mcmv and wheat streak mosaic rymovirus (wsmv) in n28ht corn produced mcmv concentrations that averaged 3.3- to 11.2-fold higher in doubly infected plants than the average concentrations in plants inoculated with mcmv. mcmv-negative sense rna concentrations were similarly increased, and the ratio of full-length to sub ...19989501040
inhibition of hepatitis b virus replication during adenovirus and cytomegalovirus infections in transgenic mice.we have previously demonstrated that hepatitis b virus (hbv) replication and gene expression are abolished in the livers of hbv transgenic mice by cytotoxic t lymphocytes (ctls) and during lymphocytic choriomeningitis virus (lcmv) infection, stimuli that trigger the production of alpha/beta interferon, gamma interferon, and tumor necrosis factor alpha in the liver. we now report that hepatic hbv replication and gene expression are inhibited by the local induction of these cytokines during adenov ...19989525579
murine cytomegalovirus inhibits interferon gamma-induced antigen presentation to cd4 t cells by macrophages via regulation of expression of major histocompatibility complex class ii-associated genes.cd4 t cells and interferon gamma (ifn-gamma) are required for clearance of murine cytomegalovirus (mcmv) infection from the salivary gland in a process taking weeks to months. to explain the inefficiency of salivary gland clearance we hypothesized that mcmv interferes with ifn-gamma induced antigen presentation to cd4 t cells. mcmv infection inhibited ifn-gamma-induced presentation of major histocompatibility complex (mhc) class ii associated peptide antigen by differentiated bone marrow macroph ...19989529320
adenovirus-mediated expression of an elastase-specific inhibitor (elafin): a comparison of different promoters.this report describes the design and construction of three recombinant adenoviruses of serotype 5 (ad5) expressing elafin (el), also called elastase-specific inhibitor. three promoters were chosen to drive the synthesis of elafin: the small (380 bp) human cytomegalovirus promoter (hcmv), the ad2 major late promoter (mlp) and the mouse cytomegalovirus (mcmv) promoter. human alveolar epithelial cells (a549), as well as rat and human primary pulmonary fibroblasts were infected with ad5-hcmv-el, ad5 ...19989614555
early atherosclerotic plaques in the aorta following cytomegalovirus infection of mice.we show here that balb/c mice inoculated with murine cytomegalovirus (mcmv) express viral antigens in the endothelial and smooth muscle cells of the aortic wall, and that accumulation of inflammatory cells in the aortic lumen, similar to that seen in early atherosclerotic lesions in humans, colocalizes with the site of virus antigen expression. immunosuppression of the mice at the time of virus infection increased the expression of viral antigens and the size of early atherosclerotic lesions in ...19989638340
systemic murine cytomegalovirus infection of mice with retrovirus-induced immunodeficiency results in ocular infection but not retinitis.experiments were performed to explore the ability of murine cytomegalovirus (mcmv) to disseminate to the eye following intravenous inoculation and to cause infection of ocular tissues and necrotizing retinitis in c57bl/6 mice with retrovirus-induced immunodeficiency syndrome (maids). although infectious virus could be detected in whole eye homogenates of mice with maids at 10 days after intravenous mcmv inoculation, a recombinant mcmv (rm461) that carries an mcmv ie1 promoter-lacz insert was use ...19989704333
wild isolates of murine cytomegalovirus induce myocarditis and antibodies that cross-react with virus and cardiac myosin.the laboratory-adapted k181 strain of murine cytomegalovirus (mcmv) induces both acute and chronic myocarditis, associated with autoantibodies to cardiac myosin, in susceptible balb/c mice. however, the k181 mcmv strain has been maintained in the laboratory for many years and may not resemble naturally occurring strains of mcmv in its ability to induce myocarditis. accordingly, six different isolates of mcmv from wild mus domesticus were compared with k181 mcmv for their ability to induce myocar ...19989741351
enhancer requirement for murine cytomegalovirus growth and genetic complementation by the human cytomegalovirus enhancer.the cytomegalovirus (cmv) enhancer is a highly complex regulatory region containing multiple elements that interact with a variety of host-encoded transcription factors. many of these sequence elements are conserved among the different species strains of cmv, although the arrangement of the various elements and overall sequence composition of the cmv enhancers differ remarkably. to delineate the importance of this region to a productive infection and to explore the possibility of generating a mu ...19989765387
apoptosis mediated by fas but not tumor necrosis factor receptor 1 prevents chronic disease in mice infected with murine cytomegalovirus.the role of fas- and tnf-receptor 1 (tnf-r1)-mediated apoptosis in the clearance of virally infected cells and in the regulation of the immune response was analyzed after murine cytomegalovirus (mcmv) infection of c57bl/6 (b6)-+/+ mice, fas-mutant b6-lpr/lpr mice, tnf-r1 knockout b6-tnfr0/0 mice, and double-deficient b6-tnfr0/0 lpr/lpr mice. there was approximately equivalent clearance of mcmv in b6-+/+, b6-tnfr0/0, and b6-lpr/lpr mice, and by day 28 no infectious virus could be detected in the ...19989769336
protective heterologous antiviral immunity and enhanced immunopathogenesis mediated by memory t cell populations.a basic principle of immunology is that prior immunity results in complete protection against a homologous agent. in this study, we show that memory t cells specific to unrelated viruses may alter the host's primary immune response to a second virus. studies with a panel of heterologous viruses, including lymphocytic choriomeningitis (lcmv), pichinde (pv), vaccinia (vv), and murine cytomegalo (mcmv) viruses showed that prior immunity with one of these viruses in many cases enhanced clearance of ...19989802982
murine cytomegalovirus induces expression and enzyme activity of cellular dihydrofolate reductase in quiescent cells.murine cytomegalovirus (mcmv) productively infects quiescent fibroblasts in which the levels of nucleoside triphosphate precursors and cell functions involved in dna metabolism are minimal. it appears that mcmv has evolved molecular pathways in order to ensure the presence of nucleoside triphosphate precursors for the viral dna polymerase. here, we report that mcmv infection of quiescent nih 3t3 cells markedly stimulates transcription, expression and activity of the cellular dihydrofolate reduct ...19989820157
(z)- and (e)-2-(hydroxymethylcyclopropylidene)-methylpurines and pyrimidines as antiviral agents.several z- and e-methylenecyclopropane nucleoside analogues were synthesized and tested for antiviral activity in vitro against human and murine cytomegalovirus (hcmv, mcmv), epstein-barr virus (ebv), varicella zoster virus (vzv), hepatitis b virus (hbv), herpes simplex virus types 1 and 2 (hsv-1, hsv-2), human herpesvirus 6 (hhv-6) and human immunodeficiency virus type 1 (hiv-1). the z-2-amino-6-cyclopropylaminopurine analogue was the most effective agent against hcmv (ec50 or ec90 0.4-2 microm ...19989875413
the role of ly49 nk cell subsets in the regulation of murine cytomegalovirus infections.the distributions and functions of nk cell subsets, as defined by the expression of ly49 nk cell receptors, were examined in murine cmv (mcmv)-infected mice. mcmv induced a reduction in nk1.1+ cell number in the spleen and an increase in the peritoneal exudate cells. within the splenic nk1.1+ population, proportional increases in ly49a+ and ly49g2+ cells but decreases in ly49c+ and ly49d+ cells were observed 3 days post-mcmv infection, but within the peritoneal nk1.1+ cell populations there were ...19999916691
immunosuppression is not required for reactivation of latent murine cytomegalovirus.we have shown, for the first time, that tnf induces expression of mcmv ie rna in the lungs of latently infected mice in the absence of immunosuppression. these initial data suggest that tnf may play an important role in the reactivation of latent mcmv, in the absence of immunosuppression, and provide a provocative insight into the mechanisms of cmv reactivation. studies are in progress to determine whether genes associated with later stages of the viral life cycle are induced by tnf and whether ...199910083617
murine viruses in an island population of introduced house mice and endemic short-tailed mice in western australia.house mice (mus domesticus) were recently introduced to thevenard island, off the northwest coast of western australia. this island is also habitat for an endangered native rodent, the short-tailed mouse (leggadina lakedownensis). concerns have been raised that house mice may pose a threat to l. lakedownensis both through competition and as a source of infection. to assess the threat to l. lakedownensis posed by viral pathogens from m. domesticus, a serological survey was conducted from 1994 to ...199910231757
the role of il-12 in the control of mcmv is fundamentally different in mice with a retroviral immunodeficiency syndrome (maids).the present study investigates the susceptibility of c57bl mice exhibiting t cell immunodeficiency and lymphadenopathy induced by lp-bm5 murine leukaemia virus (maids) to murine cytomegalovirus (mcmv). treatment of normal (m-) mice with anti-il-12 increased the contribution of igg1 to the hypergammaglobulinaemia induced by mcmv, consistent with a shift towards a th2 phenotype. this impaired control of early mcmv replication in the liver, with little effect in the spleen. control of hepatic infec ...199910234548
the association between murine cytomegalovirus induced hepatitis and the accumulation of oval cells.the accumulation of oval cells is an early event in the development of hepatocellular carcinoma induced by certain experimental regimes involving hepatocarcinogens. oval cells have also been observed during chronic hepatitis induced by alcohol and iron overload. in this study, livers of murine cytomegalovirus (mcmv) infected mice were examined to determine whether hepatitis induced by this virus could initiate oval cell proliferation. balb/c and c57bl/6 mice were infected with mcmv and studied 4 ...199810319024
replication of murine cytomegalovirus in differentiated macrophages as a determinant of viral pathogenesis.blood monocytes or tissue macrophages play a pivotal role in the pathogenesis of murine cytomegalovirus (mcmv) infection, providing functions beneficial to both the virus and the host. in vitro and in vivo studies have indicated that differentiated macrophages support mcmv replication, are target cells for mcmv infection within tissues, and harbor latent mcmv dna. however, this cell type presumably initiates early, antiviral immune responses as well. in addressing this paradoxical role of macrop ...199910364349
sequence requirements for the nuclear localization of the murine cytomegalovirus m44 gene product pp50.the murine cytomegalovirus (mcmv) m44 gene product pp50 is normally present in the nuclei of virus-infected cells. during transient expression of pp50 in cos-1 cells, the phosphoprotein was readily detectable in the nuclei, indicating that it possesses a nuclear localization signal (nls). studies on the subcellular locations of n- and c-terminal deletion mutants of pp50 suggested that alterations in both the c terminus and the highly conserved n-terminal domains of pp50 affect nuclear localizati ...199910364488
cytomegaloviral control of mhc class i function in the mouse.cytomegaloviruses (cmvs) represent prototypic viruses of the beta-subgroup of herpesviruses. murine cytomegalovirus (mcmv) infects mice as its natural host. among viruses, cmvs have evolved the most extensive genetic repertoire to subvert mhc class i functions. to date three mcmv proteins have been identified which affect mhc i complexes. they are encoded by members of large virus-specific gene families located at either flanking region of the 235 kb mcmv genome. the mhc i subversive genes belon ...199910399073
the murine cytomegalovirus chemokine homolog, m131/129, is a determinant of viral pathogenicity.chemokines are important mediators of the early inflammatory response to infection and modify a wide range of host immune responses. functional homologs of cellular chemokines have been identified in a number of herpesviruses, suggesting that the subversion of the host chemokine response contributes to the pathogenesis of these viruses. transcriptional and reverse transcription-pcr analyses demonstrated that the murine cytomegalovirus (mcmv) chemokine homolog, m131, was spliced at the 3' end to ...199910400778
systematic excision of vector sequences from the bac-cloned herpesvirus genome during virus reconstitution.recently the mouse cytomegalovirus (mcmv) genome was cloned as an infectious bacterial artificial chromosome (bac) (m. messerle, i. crnkovic, w. hammerschmidt, h. ziegler, and u. h. koszinowski, proc. natl. acad. sci. usa 94:14759-14763, 1997). the virus obtained from this construct is attenuated in vivo due to deletion of viral sequences and insertion of the bac vector. we reconstituted the full-length mcmv genome and flanked the bac vector with identical viral sequences. this new construct rep ...199910400809
transcriptional analysis of the murine cytomegalovirus hindiii-i region: identification of a novel immediate-early gene region.cytomegaloviruses likely encode numerous gene products involved in regulating virus-host cell interactions and pathogenesis. we previously identified a region of murine cytomegalovirus (mcmv) within hindiii-j and -i that regulates pathogenesis of the virus [open reading frames (orfs) m139-m141] or is likely required for mcmv replication (orfs m142 and m143). as a prerequisite for further studies on the structure and function of this gene region, we mapped the transcripts encoded within mcmv hind ...199910405367
cadaveric skin allograft-associated cytomegalovirus transmission in a mouse model of thermal injury.as a routine procedure to provide temporary coverage for burn wounds, cadaveric skin allografts have been used in patients with massive thermal injuries. in this study, cmv infection associated with skin grafting was investigated. graft-associated cmv transmission was shown in a mouse model of thermal injury. skins from mice 100 days after a nonlethal dose of murine cmv (mcmv) infection contained mcmv dna and mrna, although the virus was not isolated from these murine skins. when these skins wer ...199910444362
efficacy of low-dose oral use of type i interferon in cytomegalovirus infections in vivo.oral administration of type i interferons (ifns; murine ifn-alpha and ifn-beta) reduces early replication of murine cytomegalovirus (mcmv) in both the spleen and liver of mcmv-infected balb/c mice. examination of a range of doses of ifn (1 to 1000 iu) showed that 10 iu administered daily for 1 week prior to virus infection was optimal for inhibition of mcmv replication. furthermore, low-dose orally administered ifn (10 iu/day) was effective in mice challenged with lethal and sublethal virus inoc ...199910476931
patchwork pattern of transcriptional reactivation in the lungs indicates sequential checkpoints in the transition from murine cytomegalovirus latency to recurrence.the lungs are a significant organ site of murine cytomegalovirus (mcmv) latency. we have shown that activity of the major immediate-early promoter (miep), which drives the transcription from the ie1-ie3 transcription unit, does not inevitably initiate the productive cycle (s. k. kurz, m. rapp, h.-p. steffens, n. k. a. grzimek, s. schmalz, and m. j. reddehase, j. virol. 73:482-494, 1999). thus, even though miep activity governed by the miep-enhancer is unquestionably the first condition for recur ...199910482614
the interferon-inducible 204 gene, a member of the ifi 200 family, is not involved in the antiviral state induction by ifn-alpha, but is required by the mouse cytomegalovirus for its replication.to examine whether ifi 200 genes are involved in antiviral state induction by ifns we expressed mutant forms capable of inactivating the endogenous p204 and analyzed replication of both rna and dna viruses following ifn-alpha treatment. inactivation of p204 does not impair replication of vesicular stomatitis virus, encephalomyocarditis virus, ectromelia virus, and herpes simplex virus 1 and does not alter an ifn-alpha induced antiviral state. by contrast, in cells lacking functional p204, mouse ...199910489335
the murine cytomegalovirus m25 open reading frame encodes a component of the tegument.the murine cytomegalovirus (mcmv) monoclonal antibody 5c7:6 was used in western analysis to probe mcmv infected murine embryo cells (mec). this antibody recognizes three virus specific polypeptides of 130, 105, and 95 kda and pulse-chase experiments demonstrated that these three proteins, although antigenically related, are distinct. the 105- and 95-kda species were expressed with early kinetics, whereas the 130-kda protein was synthesized as a true late. by screening a lambdagt11 mcmv cdna libr ...199910502507
the immunoevasive function encoded by the mouse cytomegalovirus gene m152 protects the virus against t cell control in vivo.cytomegaloviruses encode numerous functions that inhibit antigen presentation in the major histocompatibility complex (mhc) class i pathway in vitro. one example is the mouse cytomegalovirus (mcmv) glycoprotein gp40, encoded by the m152 gene, which selectively retains murine but not human mhc class i complexes in the endoplasmic reticulum-golgi intermediate compartment/cis-golgi compartment (ziegler, h., r. thäle, p. lucin, w. muranyi, t. flohr, h. hengel, h. farrell, w. rawlinson, and u.h. kosz ...199910544200
the role of endogenous interleukin-12 in resistance to murine cytomegalovirus (mcmv) infection and a novel action for endogenous il-12 p40.biologically active interleukin-12 (il-12), comprising a 40 kda subunit (p40) covalently linked to a 35 kda subunit (p35), is produced in response to a range of infectious stimuli. here, we demonstrate that mice deficient in either il-12 p40 (p40-/-) or il-12 p35 (p35-/-) are susceptible to murine cytomegalovirus (mcmv) infection in terms of survival (balb/c p35-/-) and viral clearance (balb/c p35-/- and balb/c p40-/-), and this susceptibility may be correlated to a deficiency in serum interfero ...199910547154
effective treatment of murine cytomegalovirus infections with methylenecyclopropane analogues of nucleosides.a number of new nucleoside analogues with a z- or e-methylenecyclopropane structure exhibited significant activity against human and murine cytomegaloviruses (hcmv, mcmv) in tissue culture that was generally comparable to, or greater than, 9-[(1-3-dihydroxy-2-propoxy)methyl]guanine (ganciclovir, gcv). several of these analogues were chosen for further evaluation of therapeutic efficacy utilizing a mcmv infection. intraperitoneal (i.p.) inoculation of 3-week-old balb/c mice with 2.0 x 10(5) plaqu ...199910551375
cytomegalovirus cell tropism, replication, and gene transfer in brain.cytomegalovirus (cmv) infects a majority of adult humans. during early development and in the immunocompromised adult, cmv causes neurological deficits. we used recombinant murine cytomegalovirus (mcmv) expressing either green fluorescent protein (gfp) or beta-galactosidase under control of human elongation factor 1 promoter or cmv immediate early-1 promoter as reporter genes for infected brain cells. in vivo and in vitro studies revealed that neurons and glial cells supported strong reporter ge ...199910594076
migration of virus-infected neuronal cells in cerebral slice cultures of developing mouse brains after in vitro infection with murine cytomegalovirus.to investigate the effect of murine cytomegalovirus (mcmv) infection on the developing mouse brain in vitro, we developed an infection system using cerebral slice cultures. using a micromanipulator, the cerebral slices from mouse embryos on day 18.5 of gestation were injected in the subventricular zone with recombinant mcmv in which the lacz gene was inserted into a late gene, and were cultured for 7 days. viral infection, detected by beta-galactosidase reaction, was developed at the injection s ...199910603034
mutagenesis of murine cytomegalovirus using a tn3-based transposon.a transposon derived from escherichia coli tn3 was introduced into the genome of murine cytomegalovirus (mcmv) to generate a pool of viral mutants. we analyzed three of the constructed recombinant viruses that contained the transposon within the m25, m27, and m155 open reading frames. our studies provide the first direct evidence to suggest that m25 and m27 are not essential for viral replication in mouse nih 3t3 cells. studies in cultured cells and balb/c mice indicated that the transposon inse ...200010639313
acute murine cytomegalovirus infection: a model for determining antiviral activity against cmv induced hepatitis.acute intraperitoneal infection of weanling balb/c mice with murine cytomegalovirus (mcmv) resulted in an inoculum titer-dependent weight loss, mortality and elevation of plasma transaminases (alt: alanine transaminase and ast: aspartate transaminase). three days post infection (p.i.) with 10(4.85) plaque forming units (pfu) there was 90% mortality with a mean death day p.i. of 4.1 +/- 0.2. plasma levels of alt and ast were elevated 24- and 15-fold, respectively. organ titers of virus (log10 pfu ...199910651067
nitric oxide increases the amount of murine cytomegalovirus-dna in mice latently infected with the virus.at 5 wk after the intraperitoneal infection of murine cytomegalovirus (mcmv) in adult (c3h/he x balb/c) f1 (cbf1) mice, mcmv-dna was noted mainly in the salivary glands (sg). since graft-versus-host reaction (gvhr) is well known as a major risk factor for cmv reactivation, parental balb/c spleen cells were then intravenously transferred to these mice to induce gvhr. a high copy number of full-length mcmv-dna was thus observed in the lungs as well as the hearts and livers at 4 to 6 wk after the c ...199910664384
vgamma1+ gammadelta t cells play protective roles at an early phase of murine cytomegalovirus infection through production of interferon-gamma.cytomegalovirus (cmv) causes severe opportunistic infection in immunocompromised hosts. the importance of conventional alphabeta t cells in protection against cmv infection has been well documented. however, the role of the second t-cell population (which express the gammadelta t-cell receptor) in cmv infection is not known. in the present study, we analysed the function and protective role of gammadelta t cells in a murine cytomegalovirus (mcmv) infection model. after intraperitoneal infection ...200010692035
murine cytomegalovirus homologues of cellular immunomodulatory genes.the study of 'molecular mimicry' or 'genetic piracy', with respect to the utilisation of cellular genes captured and modified during the course of virus evolution, has been an area of increasing research with the expansion in virus genome sequencing. examples of cellular immunomodulatory genes which have been captured from hosts have been identified in a number of viruses. this review concentrates upon studies of murine cytomegalovirus (mcmv), investigating the functions of viral genes homologou ...199910702715
antigen presenting cells expressing fas ligand down-modulate chronic inflammatory disease in fas ligand-deficient mice.we assessed the effect of modified antigen presenting cells (apcs) expressing high levels of fas ligand (apc-fasl) on post-viral chronic inflammatory disease. fasl-deficient b6-gld/gld mice infected with murine cytomegalovirus (mcmv) cleared the virus from their lungs, kidneys, and livers within 2 weeks of infection. however, inflammation persisted in these organs for more than 8 weeks, with a chronically increased t-cell response to mcmv-infected apcs and production of autoantibodies. administr ...200010727450
development of a highly sensitive quantitative competitive pcr assay for the detection of murine cytomegalovirus dna.viral persistence and molecular latency are characteristic of infection by the human cytomegalovirus (hcmv). using the murine cytomegalovirus (mcmv) as a model for human infection, a quantitative-competitive polymerase chain reaction (qc-pcr) assay was developed to detect and quantify mcmv-dna in the salivary glands of infected mice. the qc-pcr detected high numbers of mcmv dna copies in the absence of infectious virus. by comparing the dna content and the results obtained from a standard semiqu ...200010785285
murine cytomegalovirus stimulates cellular thymidylate synthase gene expression in quiescent cells and requires the enzyme for replication.herpesviruses accomplish dna replication either by expressing their own deoxyribonucleotide biosynthetic genes or by stimulating the expression of the corresponding cellular genes. cytomegalovirus (cmv) has adopted the latter strategy to allow efficient replication in quiescent cells. in the present report, we show that murine cmv (mcmv) infection of quiescent fibroblasts induces both mrna and protein corresponding to the cellular thymidylate synthase (ts) gene, which encodes the enzyme that cat ...200010799571
in vitro activities of methylenecyclopropane analogues of nucleosides and their phosphoralaninate prodrugs against cytomegalovirus and other herpesvirus infections.human cytomegalovirus (hcmv) infection does not generally cause problems in the immunocompetent adult but can result in severe clinical disease in the fetus, neonate, and immunocompromised host. ganciclovir (gcv), the agent currently used to treat most hcmv infections, has resulted in much therapeutic success; however, efficacy remains suboptimal. therefore, there is still a need to develop new compounds for use against hcmv infections. in the present study, several z- and e-series methylenecycl ...200010817700
murine cytomegalovirus replication in salivary glands is controlled by both perforin and granzymes during acute infection.the course of mouse cytomegalovirus (mcmv) infection was compared between wild-type and mutant c57bl / 6 (b6) mice deficient in either rag-2, perforin, granzyme a, granzyme b or combinations thereof at two time points post infection (p. i.). at day 15 p. i., virus titers were similarly elevated in salivary glands of all mutant, but not wild-type b6 mice and undetectable in lung and spleen tissues of any of the mouse strains. significant pathological alterations were only seen in salivary glands ...200010820381
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
protective effect of black seed oil from nigella sativa against murine cytomegalovirus infection.in this study, antiviral effect of black seed oil (bso) from nigella sativa was investigated using murine cytomegalovirus (mcmv) as a model. the viral load and innate immunity mediated by nk cells and mφ during early stage of the infection were analyzed. intraperitoneal (i.p.) administration of bso to balb/c mice, a susceptible strain of mcmv infection, strikingly inhibited the virus titers in spleen and liver on day 3 of infection with 1x10(5) pfu mcmv. this effect coincided with an increas ...200010884593
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
synthesis and enantioselectivity of the antiviral effects of (r,z)-,(s,z)-methylenecyclopropane analogues of purine nucleosides and phosphoralaninate prodrugs: influence of heterocyclic base, type of virus and host cells.a series of r and s enantiomers of 2-aminopurine methylenecyclopropane analogues of nucleosides was synthesized. two diastereoisomeric lipophilic phosphate prodrugs derived from r and s enantiomers of 2,6-diaminopurine analogue were also prepared. enantioselectivity (diastereoselectivity in case of prodrugs) of in vitro antiviral effects was investigated with human and murine cytomegalovirus (hcmv and mcmv, respectively), herpes simplex virus types 1 and 2 (hsv-1 and hsv-2, respectively), human ...200010901290
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
immunization with dna, adenovirus or both in biodegradable alginate microspheres: effect of route of inoculation on immune response.to determine the potential for biodegradable alginate microspheres to be used as a delivery vehicle for dna based vaccines, we constructed a plasmid, pmne-gal-sv40, containing the bacterial beta-galactosidase (lacz) gene under the control of the murine cytomegalovirus (mcmv) immediate-early promoter and the simian virus 40 (sv40) polyadenylation signal. the effect of the route of administration and co-administration of adenovirus on systemic and mucosal immune responses were investigated. mice w ...200010930680
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
generation of mutant murine cytomegalovirus strains from overlapping cosmid and plasmid clones.we have developed a cosmid and plasmid system to generate mutant strains of murine cytomegalovirus (mcmv). the system is based on a series of seven overlapping cosmid clones that regenerate mcmv when cotransfected into mouse cells. the unaltered cosmids produce mcmv that is indistinguishable from wild-type mcmv based on restriction enzyme digest patterns of virus dna and growth rates both in vitro and in vivo. analysis of viral dna from plaque-purified recombinant isolates taken from in vitro an ...200010982341
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
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
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
mouse cytomegalovirus in developing brain tissue: analysis of 11 species with gfp-expressing recombinant virus.cytomegaloviruses (cmvs) are species-specific large double-stranded dna viruses. mouse and human cmvs have a similar morphology, similar gene sequence, and exert similar cellular effects, but the replication of the virus outside its primary host species is limited. this may confer upon cmv certain advantages for expression of foreign genes or cellular labels in brain cells of nonhost species. we examined the ability of recombinant mouse (m)cmv expressing green fluorescent protein (gfp) to serve ...200011056464
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
enrichment of immediate-early 1 (m123/pp89) peptide-specific cd8 t cells in a pulmonary cd62l(lo) memory-effector cell pool during latent murine cytomegalovirus infection of the lungs.interstitial cytomegalovirus (cmv) pneumonia is a clinically relevant complication in recipients of bone marrow transplantation (bmt). recent data for a model of experimental syngeneic bmt and concomitant infection of balb/c mice with murine cmv (mcmv) have documented the persistence of tissue-resident cd8 t cells after clearance of productive infection of the lungs (j. podlech, r. holtappels, m.-f. pahl-seibert, h.-p. steffens, and m. j. reddehase, j. virol. 74:7496-7507, 2000). it was proposed ...200011090146
expression of an altered ribonucleotide reductase activity associated with the replication of murine cytomegalovirus in quiescent fibroblasts.ribonucleotide reductase (rnr) is an essential enzyme for the de novo synthesis of both cellular and viral dna and catalyzes the conversion of ribonucleoside diphosphates into the corresponding deoxyribonucleoside diphosphates. the enzyme consists of two nonidentical subunits, termed r1 and r2, whose expression is very low in resting cells and maximal in s-phase cells. here we show that murine cytomegalovirus (mcmv) replication depends on ribonucleotide reduction since it is prevented by the rnr ...200011090153
dominance of virus over host factors in cross-species activation of human cytomegalovirus early gene expression.human cytomegalovirus (hcmv) exhibits a highly restricted host range. in this study, we sought to examine the relative significance of host and viral factors in activating early gene expression of the hcmv ul54 (dna polymerase) promoter in murine cells. appropriate activation of the ul54 promoter at early times is essential for viral dna replication. to study how the hcmv ul54 promoter is activated in murine cells, a transgenesis system based on yeast artificial chromosomes (yacs) was establishe ...200111119570
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
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
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
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
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
rat cytomegalovirus major immediate-early enhancer switching results in altered growth characteristics.it has been hypothesized that the major immediate-early (mie) enhancer of cytomegalovirus (cmv) is important in determining virus tropism and latency because of its essential role in initiating the cascade of early gene expression necessary for virus replication. although rat cmv (rcmv) and murine cmv (mcmv) exhibit extreme species specificity in vivo, they differ in their ability to replicate in tissue culture. mcmv can replicate in a rat embryo fibroblast (ref) cell line while rcmv does not gr ...200111333888
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
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