| 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 ... | 2000 | 11005206 |
| 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 ... | 2000 | 11090146 |
| 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 ... | 2000 | 11090153 |
| 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 ... | 2000 | 11218223 |
| 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 ... | 2001 | 11413295 |
| murine cytomegalovirus is regulated by a discrete subset of natural killer cells reactive with monoclonal antibody to ly49h. | antiviral roles of natural killer (nk) cell subsets were examined in c57bl/6 mice infected with murine cytomegalovirus (mcmv) and other viruses, including lymphocytic choriomeningitis virus (lcmv), vaccinia virus (vv), and mouse hepatitis virus (mhv). each virus vigorously induced an nk cell infiltrate into the peritoneal cavity and liver, causing some redistributions of nk cell subsets defined by monoclonal antibody (mab) directed against ly49a, c/i, d, and g2. striking results were seen with a ... | 2001 | 11435470 |
| characterization of nuclear rnases that cleave hepatitis b virus rna near the la protein binding site. | hepatitis b virus (hbv) rna is downregulated by inflammatory cytokines induced in the liver by adoptively transferred hbv-specific cytotoxic t lymphocytes (ctls) and during murine cytomegalovirus (mcmv) infections of the livers of hbv transgenic mice. the disappearance of hbv rna is tightly associated with the cytokine-induced proteolytic cleavage of a previously defined hbv rna-binding protein known as la autoantigen. la binds to a predicted stem-loop structure at the 5' end of the posttranscri ... | 2001 | 11435567 |
| in vitro and in vivo activity of 1-o-hexadecylpropanediol-3-phospho-ganciclovir and 1-o-hexadecylpropanediol-3-phospho-penciclovir in cytomegalovirus and herpes simplex virus infections. | human cytomegalovirus (hcmv) and herpes simplex virus (hsv) can cause a wide variety of clinical manifestations in man. ganciclovir (gcv) is effective against hcmv infection when administered by the intravenous route and may be used orally in large doses for prophylaxis of hcmv infections in organ transplantation patients and in aids patients. in previous studies with acyclovir (acv), we found that covalent attachment of an alkyl glycerol phosphate moiety greatly increased oral bioavailability a ... | 2001 | 11437323 |
| the interferon-inducible 204 gene is transcriptionally activated by mouse cytomegalovirus and is required for its replication. | infection of cells with viable or uv-inactivated murine cytomegalovirus (mcmv) increased the ifn-inducible 204 gene at both the mrna and the protein levels. the activity of a reporter gene driven by the mouse ifi204 promoter induced following virus infection showed that this increase was due to transcriptional activation. moreover, facs analysis of infected mouse embryo fibroblasts (mef) stably transfected with a p204-dominant-negative mutant (p204dmmef) revealed that they do not accumulate at t ... | 2001 | 11485393 |
| a novel nonnucleoside inhibitor specifically targets cytomegalovirus dna maturation via the ul89 and ul56 gene products. | 3-hydroxy-2,2-dimethyl-n-[4([[5-(dimethylamino)-1-naphthyl]sulfonyl]amino)-phenyl]propanamide (bay 38-4766) is a novel selective nonnucleoside inhibitor of cytomegalovirus (cmv) replication with an excellent safety profile. this compound and structural analogues inhibit neither viral dna synthesis nor viral transcription and translation. accumulation of dense bodies and noninfectious enveloped particles coincides with inhibition of both concatemer processing and functional cleavage at intergenom ... | 2001 | 11533171 |
| the murine cytomegalovirus immune evasion protein m4/gp34 forms biochemically distinct complexes with class i mhc at the cell surface and in a pre-golgi compartment. | we have recently demonstrated that the murine cmv (mcmv) gene m4 is an immune evasion gene that protects mcmv-infected targets from some virus-specific ctl clones. m4 encodes m4/gp34, a 34-kda glycoprotein that binds to major histocompatibility complex class i in the endoplasmic reticulum and forms a detergent-stable complex that is exported to the surface of the cell. to investigate how m4/gp34 promotes ctl evasion, we analyzed the assembly and export of m4/gp34-k(b) complexes. we found that 50 ... | 2001 | 11564807 |
| nk cell functions restrain t cell responses during viral infections. | nk cell functions for regulation of t cell responses were evaluated during acute viral infections. in vivo depletion studies established that the presence of nk cells in murine cytomegalovirus (mcmv)-infected immunocompetent mice negatively affected cd4 and cd8 t cell ifn-gamma expression, bromodeoxyuridine (brdu) incorporation, and expansion. to evaluate nk cell effects, under conditions when nk cells do not control viral replication, experiments were performed using lymphocytic choriomeningiti ... | 2001 | 11592081 |
| nitric oxide targets bronchiolar epithelial cells in murine cytomegalovirus-associated disease in lungs that are free of the virus. | at 4 weeks after intraperitoneal (i.p.) injection of 0.2ld50 (50% lethal dose) of murine cytomegalovirus (mcmv) in adult balb/c mice, productive virus and the viral dna were detected only in the salivary glands, but not in the lungs. a single i.p. injection of anti-cd3 mab to these mice provoked pulmonary lesions, which included a thickening of the interstitium and peribronchiolar areas, accompanied with a cellular infiltration in those areas. as a result, half of the mice died. in a histochemic ... | 2001 | 11676413 |
| secreted virus-encoded proteins reflect murine cytomegalovirus productivity in organs. | mouse infection with murine cytomegalovirus (mcmv) is an established model for studying human cytomegalovirus infection. in this study, the relationship was analyzed between mcmv activity in organs of infected mice and the presence of infectious virus (viremia), viral genomes (dnaemia), or secreted virus-encoded proteins in the blood. for the latter, 2 recombinant viruses were constructed that encode for the hepatitis b virus surface antigen and the secreted alkaline phosphatase, respectively, a ... | 2001 | 11679922 |
| viral escape mechanisms--escapology taught by viruses. | viruses have 'studied' immunology over millions of years of coevolution with their hosts. during this ongoing education they have developed countless mechanisms to escape from the host's immune system. to illustrate the most common strategies of viral immune escape we have focused on two murine models of persistent infection, lymphocytic choriomeningitis virus (lcmv) and murine cytomegalovirus (mcmv). lcmv is a fast replicating small rna virus with a genome prone to mutations. therefore, lcmv es ... | 2001 | 11703537 |
| cytomegalovirus infection accelerates inflammation in vascular tissue overexpressing monocyte chemoattractant protein-1. | cardiovascular disease is the leading cause of mortality in the united states. atherosclerosis is responsible for most of this pathology and is an inflammatory disease with multiple cytokines and adhesion molecules expressed during atherogenesis. cytomegalovirus (cmv), monocytes, and monocyte chemoattractant protein-1 (mcp-1) have all been implicated in human atherogenesis. a transgenic mouse overexpressing mcp-1 in the myocardium and pulmonary arteries develops myocarditis and pulmonary vascula ... | 2001 | 11739289 |
| immunomodulation of murine cytomegalovirus-induced myocarditis in mice treated with lipopolysaccharide and tumor necrosis factor. | murine cytomegalovirus (mcmv) infection of balb/c mice produces acute and chronic myocarditis similar to clinical disease in humans. in contrast, mcmv-infected c57bl/6 mice develop only mild acute myocarditis. we have investigated the effect of administration of the immunomodulator lipopolysaccharide (lps) on the development of postviral myocarditis in mice. lps exacerbated heart inflammation in both strains of mcmv-infected mice, with normally resistant c57bl/6 mice developing chronic myocardit ... | 2001 | 11747356 |
| early gene m18, a novel player in the immune response to murine cytomegalovirus. | the identification of all antigenic peptides encoded by a pathogen, its t cell 'immunome', is a research aim for rational vaccine design. screening of proteome-spanning peptide libraries or computational prediction is used to identify antigenic peptides recognized by cd8 t cells. based on their high coding capacity, cytomegaloviruses (cmvs) could specify numerous antigenic peptides. yet, current evidence indicates that the memory cd8 t cell response in a given haplotype is actually focused on a ... | 2002 | 11807223 |
| interferon alpha/beta and interleukin 12 responses to viral infections: pathways regulating dendritic cell cytokine expression in vivo. | interferon (ifn)-alpha/beta and interleukin (il)-12 are cytokines critical in defense against viruses, but their cellular sources and mechanisms of regulation for in vivo expression remain poorly characterized. the studies presented here identified a novel subset of dendritic cells (dcs) as major producers of the cytokines during murine cytomegalovirus (mcmv) but not lymphocytic choriomeningitis virus (lcmv) infections. these dcs differed from those activated by toxoplasma antigen but were relat ... | 2002 | 11854364 |
| failure to infect embryos after virus injection in mouse zygotes. | the intracytoplasmic injection of sperm raises the problem that viral elements may be transported into the oocyte by the spermatozoon or the surrounding medium. it also raises questions about how the developing zygote will behave. | 2002 | 11870132 |
| broad-spectrum antiviral activity of pnu-183792, a 4-oxo-dihydroquinoline, against human and animal herpesviruses. | we identified a novel class of 4-oxo-dihydroquinolines represented by pnu-183792 which specifically inhibit herpesvirus polymerases. pnu-183792 was highly active against human cytomegalovirus (hcmv, ic(50) value 0.69 microm), varicella zoster virus (vzv, ic(50) value 0.37 microm) and herpes simplex virus (hsv, ic(50) value 0.58 microm) polymerases but was inactive (ic(50) value >40 microm) against human alpha (alpha), gamma (gamma), or delta (delta) polymerases. in vitro antiviral activity again ... | 2002 | 11888654 |
| development of a vaccine against murine cytomegalovirus (mcmv), consisting of plasmid dna and formalin-inactivated mcmv, that provides long-term, complete protection against viral replication. | we previously demonstrated that immunization of mice with plasmid dnas (pdnas) expressing the murine cytomegalovirus (mcmv) genes ie1-pp89 and m84 provided synergistic protection against sublethal viral challenge, while immunization with plasmids expressing putative virion proteins provided no or inconsistent protection. in this report, we sought to augment protection by increasing the breadth of the immune response. we identified another mcmv gene (m04 encoding gp34) that provided strong and co ... | 2002 | 11967299 |
| processing and presentation of murine cytomegalovirus porfm164-derived peptide in fibroblasts in the face of all viral immunosubversive early gene functions. | cd8 t cells are the principal effector cells in the resolution of acute murine cytomegalovirus (mcmv) infection in host organs. this undoubted antiviral and protective in vivo function of cd8 t cells appeared to be inconsistent with immunosubversive strategies of the virus effected by early (e)-phase genes m04, m06, and m152. the so-called immune evasion proteins gp34, gp48, and gp37/40, respectively, were found to interfere with peptide presentation at different steps in the major histocompatib ... | 2002 | 12021337 |
| mcmv glycoprotein gp40 confers virus resistance to cd8+ t cells and nk cells in vivo. | the susceptibility of certain inbred mouse strains to murine cytomegalovirus (mcmv) is related to their inability to generate a strong natural killer (nk) cell response. we addressed here whether the mcmv susceptibility of the balb/c strain is due to viral functions that control nk cell activation in a strain-specific manner. mcmv expresses two proteins, gp48 and gp40, that are encoded by the genes m06 and m152, respectively; they down-regulate major histocompatibility complex (mhc) class i expr ... | 2002 | 12021778 |
| mechanisms of human cytomegalovirus persistence and latency. | human cytomegalovirus (hcmv) is a ubiquitous beta-herpesvirus that causes severe disease primarily in immunosuppressed individuals. a major characteristic of hcmv with obvious clinical importance is the ability of the virus to establish lifelong infection within the host following the initial acute infection. one strategy used by hcmv to maintain itself within the host is the establishment of cellular sites of persistent infection and viral latency. recent studies have identified endothelial cel ... | 2002 | 12045013 |
| characterisation of murine cytomegalovirus myocarditis: cellular infiltration of the heart and virus persistence. | myocarditis triggered by a viral infection has integral viral and immunological aspects associated with the pathogenesis of disease. the present study was performed to analyse the cellular inflammatory response in the heart and cytomegalovirus replication during the development of myocarditis in vivo. we examined murine cytomegalovirus in an animal model of myocarditis using both susceptible balb/c and resistant c57bl/6 mice. the heart infiltrating cells of balb/c mice were found to comprise pre ... | 2002 | 12054850 |
| recognition of a virus-encoded ligand by a natural killer cell activation receptor. | natural killer (nk) cells express inhibitory and activation receptors that recognize mhc class i-like molecules on target cells. these receptors may be involved in the critical role of nk cells in controlling initial phases of certain viral infections. indeed, the ly49h nk cell activation receptor confers in vivo genetic resistance to murine cytomegalovirus (mcmv) infections, but its ligand was previously unknown. herein, we use heterologous reporter cells to demonstrate that ly49h recognizes mc ... | 2002 | 12060703 |
| type i interferon gene therapy protects against cytomegalovirus-induced myocarditis. | type i interferons (ifns) are produced early in response to viral infection and modulate adaptive immunity. previously we demonstrated localized protection against murine cytomegalovirus (mcmv) infection in ifn dna-inoculated mice. here we examine the effect of seven ifn subtypes (ifna1, a2, a4, a5, a6, a9 and b), administered by dna inoculation, on systemic mcmv infection and myocarditis. ifn transgene expression altered the pathogenesis of mcmv infection with regard to virus titre and myocardi ... | 2002 | 12100732 |
| human cytomegalovirus persistence and latency in endothelial cells and macrophages. | human cytomegalovirus (hcmv) is a clinically significant herpes virus that maintains a lifelong infection in the host. hcmv infection of endothelial cells and macrophages plays an important role in the establishment of latency and persistence, which appears critical for the maintenance of hcmv within the host. hcmv infection is profoundly influenced by endothelial cell origin and the specific pathway of macrophage differentiation. multiple hcmv genes appear to be involved in enabling virus repli ... | 2002 | 12160860 |
| persisting murine cytomegalovirus can reactivate and has unique transcriptional activity in ocular tissue. | cytomegalovirus (cmv) retinitis is an important ocular complication in human immunodeficiency virus-infected individuals and the leading cause of blindness in those not undergoing highly active antiretroviral therapy. murine cmv (mcmv) infection of mice has been shown to be a useful small-animal model for the study of cmv pathogenesis in the eye. the purpose of this study was to evaluate cmv persistence in ocular tissue and to determine the potential for reactivation. following subretinal inocul ... | 2002 | 12186900 |
| innate immune responses to cytomegalovirus infection in the developing mouse brain and their evasion by virus-infected neurons. | cytomegalovirus (cmv) is the most frequent infectious cause of developmental brain disorders in humans. here we show the role of innate immune responses caused by natural killer (nk) cells and nitric oxide (no) derived from brain macrophages during murine cmv (mcmv) infection of the developing brain. viral replication in the brain of newborn mice was significantly enhanced by administration of anti-asialo-gm1 antibody, specific for nk cells, or l-n6-(1-imminoethyl)-lysine, a specific inhibitor o ... | 2002 | 12213720 |
| ecological basis for fertility control in the house mouse (mus domesticus) using immunocontraceptive vaccines. | laboratory studies confirm the potential for fertility control in the house mouse mus domesticus using mouse cytomegalovirus (mcmv) as a vector for an immunocontraceptive vaccine. this article presents an overview of key results from research in australia on enclosed and field populations of mice and the associated epidemiology of mcmv. the virus is geographically widespread in australia. it also persists in low population densities of mice, although if population densities are low for at least ... | 2002 | 12220162 |
| synergy of type i interferon-a6 and interferon-b naked dna immunotherapy for cytomegalovirus infection. | delivery of type i ifn transgenes by naked dna immunization can protect against cytomegalovirus infection and myocarditis. here, we investigate ifn transgene expression, antiviral efficacy, and immunomodulation of myocarditis using various treatment regimes in a mouse cmv model. in vivo expression of the ifn transgene was observed in the sera for 35 days post-dna inoculation. prophylactic ifn-a6 and ifn-b dna treatment for 14 days prior to murine cytomegalovirus (mcmv) infection was more efficac ... | 2002 | 12225378 |
| mouse models of cytomegalovirus latency: overview. | background: the molecular regulation of viral latency and reactivation is a central unsolved issue in the understanding of cytomegalovirus (cmv) biology. like human cmv (hcmv), murine cmv (mcmv) can establish a latent infection in cells of the myeloid lineage. since mcmv genome remains present in various organs after its clearance from hematopoietic cells first in bone marrow and much later in blood, there must exist one or more widely distributed cell type(s) representing the cellular site(s) o ... | 2002 | 12361754 |
| a model for reactivation of cmv from latency. | reactivation of cmv from latency results in serious morbidity and mortality in immunocompromised transplant recipients. the mechanism by which cmv reactivates from latency has not been well understood. | 2002 | 12361763 |
| apoptosis in the retina during mcmv retinitis in immunosuppressed balb/c mice. | cytomegalovirus (cmv) retinitis is the most common opportunistic ocular infection observed in immunosuppressed (is) adult and pediatric patients. due to the species restriction of the cytomegaloviruses, mice infected with murine cmv (mcmv) have been used to study the pathogenesis of cmv retinitis. | 2002 | 12361764 |
| mcmv infection increases early t-lymphocyte influx in atherosclerotic lesions in apoe knockout mice. | multiple epidemiological studies have suggested that cytomegalovirus (cmv) infection is associated with atherosclerotic disease. however, conclusive proof that the virus is directly related to the progression of the disease is still lacking. | 2002 | 12361766 |
| coimmunisation with type i ifn genes enhances protective immunity against cytomegalovirus and myocarditis in gb dna-vaccinated mice. | viral dna vaccines encoding the glycoprotein b (gb) of cytomegalovirus provide partial protective immunity upon challenge with infectious virus. although it is known that type i ifn can stimulate the adaptive immune response, their direct use in vaccines has been limited. here we show that coimmunisation of type i ifn and gb cmv dna constructs enhances protective immunity in mice. in vivo expression of ifn transgenes ranged from 1.2 to 2.0 x 10(4) iu/g tibialis anterior muscle. viral titre in ma ... | 2002 | 12365002 |
| the amount of immature glial cells in organotypic brain slices determines the susceptibility to murine cytomegalovirus infection. | cytomegalovirus (cmv) is the most common infectious cause of congenital anomalies of the brain and also causes brain damage in immunocompromised individuals. we investigated the effects of murine cytomegalovirus (mcmv) infection on the developing mouse brain in terms of susceptible cells and age-related resistance to mcmv in brain slice cultures. brain slices from balb/c mice at different developmental stages were infected with recombinant mcmv in which the lacz gene was inserted into a late gen ... | 2002 | 12379769 |
| human cytomegalovirus infection induces cellular thymidylate synthase gene expression in quiescent fibroblasts. | productive infection of non-proliferating cells by cytomegalovirus (cmv) requires the coordinated stimulation of host biochemical pathways that prepare cells to synthesize dna. here we illustrate the ability of human cmv (hcmv) to stimulate cellular thymidylate synthase (ts) gene expression in quiescent human embryonic lung fibroblasts. ts mrna and protein levels are nearly undetectable in quiescent cells, but are greatly increased following hcmv infection. inhibition of ts activity was shown to ... | 2002 | 12466474 |
| effective inhibition of k(b)- and d(b)-restricted antigen presentation in primary macrophages by murine cytomegalovirus. | macrophages play an important role in murine cytomegalovirus (mcmv) infection in vivo, both in disseminating infection and in harboring latent virus. mcmv encodes three immune evasion genes (m4, m6, and m152) that interfere with the ability of cytotoxic t cells (ctl) to detect virus-infected fibroblasts, but the efficacy of immune evasion in macrophages has been controversial. here we show that mcmv immune evasion genes function in h-2(b) primary bone marrow macrophages (bmmphi) in the same way ... | 2003 | 12477835 |
| mouse cytomegalovirus immediate-early protein 1 binds with host cell repressors to relieve suppressive effects on viral transcription and replication during lytic infection. | herpesviruses start their transcriptional cascade at nuclear domain 10 (nd10). the deposition of virus genomes at these nuclear sites occurs due to the binding of the interferon-inducible repressor protein promyelocytic leukemia protein (pml) and/or daxx to a viral dna-protein complex. however, the presence of repressive proteins at the nuclear site of virus transcription has remained unexplained. we investigated the mouse cytomegalovirus (mcmv) immediate-early 1 protein (ie1), which is necessar ... | 2003 | 12502852 |
| [primary studies on the establishment of cytomegalovirus murine model]. | intraperitoneal inoculation of murine cytomegalovirus(mcmv) into balb/c mice at age of 4 weeks resulted in acute mcmv infection of the mice. the infected mice had body weight reduction, growth retardation, salivary gland swelling and death. a lethal dose was 5 x 10(6) pfu/ml of mcmv. virus could be recovered from salivary gland and the infectivity titer of mcmv reached to a high titer of 2 x 10(5) pfu/ml. plaque formation of mcmv in 3t3/swiss albino cells was identified. histopathological examin ... | 1998 | 12515174 |
| vigorous innate and virus-specific cytotoxic t-lymphocyte responses to murine cytomegalovirus in the submaxillary salivary gland. | to better understand the immunological mechanisms that permit prolonged shedding of murine cytomegalovirus (mcmv) from the salivary gland, the phenotypic and functional characteristics of leukocytes infiltrating the submaxillary gland (smg) were analyzed in infected balb/c mice. a robust innate immune response, comprised of cd11c+ major histocompatibility complex class ii+ cd11b- cd8alpha+ dendritic cells and gamma/delta t-cell receptor-bearing cd3+ t cells was prominent through at least 28 days ... | 2003 | 12525604 |
| activation of natural killer (nk) t cells during murine cytomegalovirus infection enhances the antiviral response mediated by nk cells. | nk1.1+ t (nkt) cells are efficient regulators of early host responses which have been shown to play a role in tumor surveillance. the relevance of nkt cells in immune surveillance of viral infections, however, is not well understood. in this study, we investigated the functional relevance of nkt cells in controlling herpesvirus infections by using challenge with murine cytomegalovirus (mcmv) as the study model. this model has proven to be one of the best systems for evaluating the role of nk cel ... | 2003 | 12525622 |
| memory inflation: continuous accumulation of antiviral cd8+ t cells over time. | cd8+ t lymphocytes play an important role in the control of intracellular pathogens during both acute and persistent infections. this is particularly true in the case of persistent herpesviruses such as human cmv, which are typified by large virus-specific cd8+ t cell populations during viral latency. to understand the origin of these populations and the factors shaping them over time, we investigated the cd8+ t cell response after murine cmv (mcmv) infection. the kinetics of the acute response ... | 2003 | 12574372 |
| in vitro and in vivo characterization of a murine cytomegalovirus with a mutation at open reading frame m166. | 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 mutants, rvm166, which contained the transposon sequence at open reading frame m166, was characterized both in tissue culture and in immunocompetent balb/c mice and immunodeficient scid mice. the viral mutant replicated as well as the wild-type smith strain in vitro in nih 3t3 cells, whereas the transposon insertion precluded the expression of ... | 2003 | 12584312 |
| an essential role of the enhancer for murine cytomegalovirus in vivo growth and pathogenesis. | the transcription of cytomegalovirus (cmv) immediate-early (ie) genes is regulated by a large and complex enhancer containing an array of binding sites for a variety of cellular transcription factors. previously, using bacterial artificial chromosome recombinants of the virus genome, it was reported that the enhancer region of murine cmv (mcmv) is dispensable but performs a key function for viral multiplication (a. angulo, m. messerle, u. h. koszinowski, and p. ghazal, j. virol. 72:8502-8509, 19 ... | 2003 | 12584345 |
| loss of the perforin cytotoxic pathway predisposes mice to experimental cytomegalovirus retinitis. | aids-related human cytomegalovirus (hcmv) retinitis continues to be a chronic ophthalmologic problem among human immunodeficiency virus type 1 (hiv-1)-infected patients who do not respond to highly active antiretroviral therapy. although hcmv retinitis occurs during hiv-1-induced immunosuppression, the precise effector mechanism(s) that fails during the immunopathogenesis of aids to allow onset and progression of hcmv retinal disease remains unclear. we therefore performed a series of experiment ... | 2003 | 12610115 |
| experimental study of mouse cytomegalovirus infected mice. | in order to investigate the human cytomegalovirus (hcmv) infection, the mouse cytomegalovirus (mcmv) infected mice were experimentally studied. 6 to 8 week old female balb/c mice with immunosuppression were selected to undergo the mcmv inoculations: intracranial inoculation and peritoneal inoculation. mcmv of the infected mice in various organs and tissues were detected by using beta-gal staining and in situ nucleic acid hybridization assay. the pathological changes were observed in he staining ... | 2002 | 12658822 |
| dendritic cells under influence of mouse cytomegalovirus have a physiologic dual role: to initiate and to restrict t cell activation. | the aim of this study is to analyze the dynamics of the mouse cytomegalovirus (mcmv)-dendritic cell (dc) interaction. immature and mature dcs derived from the mouse stem cell line factor-dependent cell paterson mixed potential were infected with a recombinant mcmv expressing green fluorescent protein. infection of immature dcs resulted in dc activation and virus production, both of which may contribute to viral dissemination. the infection of mature dcs was nonproductive and was restricted to im ... | 2003 | 12660946 |
| role of murine cytomegalovirus us22 gene family members in replication in macrophages. | the large cytomegalovirus (cmv) us22 gene family, found in all betaherpesviruses, comprises 12 members in both human cytomegalovirus (hcmv) and murine cytomegalovirus (mcmv). conserved sequence motifs suggested a common ancestry and related functions for these gene products. two members of this family, m140 and m141, were recently shown to affect mcmv replication on macrophages. to test the role of all us22 members in cell tropism, we analyzed the growth properties in different cell types of mcm ... | 2003 | 12719548 |
| mucosal immunization with a replication-deficient adenovirus vector expressing murine cytomegalovirus glycoprotein b induces mucosal and systemic immunity. | the murine cytomegalovirus (mcmv) glycoprotein b (gb) gene was expressed in an adenovirus replication-deficient vector. this virus, designated ad-gb, was used to immunize balb/c and b6 mice by the intranasal (i.n.) route to induce an immune response. following primary immunization, antibody was detected in serum of 100% of vaccinees, as well as the bronchoalveolar lavage, fecal suspensions and vaginal washings. the viral titer of lung and salivary gland of vaccinees 10 days after intranasal chal ... | 2003 | 12744900 |
| nkg2d-mediated natural killer cell protection against cytomegalovirus is impaired by viral gp40 modulation of retinoic acid early inducible 1 gene molecules. | natural killer (nk) cells play a critical role in the innate immune response against cytomegalovirus (cmv) infections. although cmv encodes several gene products committed to evasion of adaptive immunity, viral modulation of nk cell activity is only beginning to be appreciated. a previous study demonstrated that the mouse cmv m152-encoded gp40 glycoprotein diminished expression of ligands for the activating nk cell receptor nkg2d on the surface of virus-infected cells. here we have defined the p ... | 2003 | 12756263 |
| dendritic cells and hcmv cross-presentation. | the outcome of a viral infection is the result of an endless fight between the organism whose task is to mount an antiviral response and the virus that adapts strategies to circumvent the host response. human cytomegalovirus (hcmv), a latent herpesvirus, can be considered as a spearhead in exploiting co-existence with the host to develop numerous immuno-evasion mechanisms. the ability of the organism to initiate a primary immune response against viruses such as hcmv is highly dependent on the ca ... | 2003 | 12797453 |
| murine cytomegalovirus abortively infects human dendritic cells, leading to expression and presentation of virally vectored genes. | dendritic cells (dc) are potent antigen-presenting cells that play a crucial role in antigen-specific immune responses. thus, the targeting of exogenous antigens to dc has become a popular approach for cancer immunotherapy and vaccine development. in this report, we studied the interplay between murine cytomegalovirus (mcmv) and human monocyte-derived dc. the results showed that an enhanced green fluorescent protein (egfp)-encoding, replication-competent mcmv vector underwent abortive infection ... | 2003 | 12805417 |
| murine cytomegalovirus with a transposon insertional mutation at open reading frame m35 is defective in growth in vivo. | we had previously constructed a pool of murine cytomegalovirus (mcmv) mutants that contained a tn3-based transposon sequence randomly inserted in the viral genome. in the study reported here, one of the mutants, rvm35, which contains the transposon insertion at open reading frame m35, was characterized both in vitro in tissue cultures and in immunocompetent balb/c and immunodeficient scid mice. our results provide the first direct evidence to suggest that m35 is not essential for viral replicati ... | 2003 | 12829814 |
| cytomegalovirus m43 gene modulates t helper cell response. | role of viral genes in modulating t helper 1 (th1) and t helper 2 (th2) balance is of principal interest in the study of cytomegalovirus (cmv) immunity. murine cmv (mcmv) mutants were used to explore a possible mechanism for the ability of virus to induce a predominant th1 response and to suppress th2 response by examining the production of th1 (ifn-gamma, il-2) and th2 (il-4, il-10) cytokines by the splenocytes of mice infected with wild type (wt) and mcmv mutants. results (n=6) show that as co ... | 2003 | 12853158 |
| vaccination of mice with bacteria carrying a cloned herpesvirus genome reconstituted in vivo. | bacterial delivery systems are gaining increasing interest as potential vaccination vectors to deliver either proteins or nucleic acids for gene expression in the recipient. bacterial delivery systems for gene expression in vivo usually contain small multicopy plasmids. we have shown before that bacteria containing a herpesvirus bacterial artificial chromosome (bac) can reconstitute the virus replication cycle after cocultivation with fibroblasts in vitro. in this study we addressed the question ... | 2003 | 12857893 |
| murine cytomegalovirus retinitis during retrovirus-induced immunodeficiency (maids) in mice: interleukin-2 immunotherapy correlates with increased intraocular levels of perforin mrna. | mice with a retrovirus-induced immunosuppression (maids) are susceptible to experimental murine cytomegalovirus (mcmv) retinitis, but can be rendered resistant to retinitis by systemic interleukin-2 (il-2) immunotherapy. experiments were performed to explore the mechanism by which il-2 treatment during maids might restore resistance to mcmv retinitis. whereas 80% of untreated maids mice were susceptible to mcmv retinitis, none (0%) of il-2-treated maids mice developed necrotizing retinitis. in c ... | 2003 | 12895694 |
| cytokine expression in murine cytomegalovirus-induced myocarditis: modulation with interferon-alpha therapy. | cytomegalovirus-induced myocarditis is largely immune-mediated. balb/c mice produced higher levels of il-4 in the heart indicative of a th2-like response. although il-6, il-10, il-18, and tnf-alpha were produced in the heart during acute infection, balb/c mice lacked a substantial il-2 and ifn-gamma response. conversely, c57bl/6 mice produced significant levels of ifn-gamma in the heart with no significant levels of il-4 or il-6, suggestive of a dominant th1-like response to virus infection. ifn ... | 2003 | 12914761 |
| molecular genetic characterization of the distal nkc recombination hotspot and putative murine cmv resistance control locus. | the nk gene complex (nkc) controls murine cytomegalovirus (mcmv) immunity through cmv1-dependent natural killer (nk) cell responses. ly49h expression correlates with cmv1 phenotypes in different inbred strains, is required for mcmv resistance in c57bl/6 (b6) mice, and its interaction with the mcmv encoded m157 protein leads to nk cell-mediated destruction of virus-infected cells. however, genetic mapping studies have previously indicated that cmv1 should reside in the d6wum9-16 nkc interval, dis ... | 2003 | 12920489 |
| murine cytomegalovirus infection inhibits tumor necrosis factor alpha responses in primary macrophages. | despite robust host immune responses the betaherpesvirus murine cytomegalovirus (mcmv) is able to establish lifelong infection. this capacity is due at least in part to the virus utilizing multiple immune evasion mechanisms to blunt host responses. macrophages are an important cell for mcmv infection, dissemination, and latency despite expression in the host of multiple cytokines, including tumor necrosis factor alpha (tnf-alpha), that can induce an antiviral state in macrophages or other cells. ... | 2003 | 12941924 |
| adenovirus expression of il-1 and nf-kappab inhibitors does not inhibit acute adenoviral-induced brain inflammation, but delays immune system-mediated elimination of transgene expression. | despite their ability to provide long-term transgene expression in the central nervous system of naïve hosts, the use of first-generation adenovirus (ad) vectors for the treatment of chronic neurological disorders is limited by peripheral immunization, which stimulates anti-adenovirus immune responses and causes severe inflammation in the central nervous system (cns) and elimination of transgene expression. the purpose of this study was to investigate the roles of nf-kappab and interleukin-1 (il ... | 2003 | 12946313 |
| quantitative measurement of infectious murine cytomegalovirus genomes in real-time pcr. | acute virus replication in murine (m) cmv infected c57bl/6 (cmv1(r)) mice is severely limited by ly49h+ nk cells, but not in mcmv infected balb/c or bxd8 (cmv1(s)) mice that lack ly49h+ nk cells. interestingly, other nk cell receptors may also play a role in mcmv immunity, as cmv encoded gp40 protein can diminish expression of protein ligands recognized by the nk cell receptor nkg2d. to determine whether other additional gene products might influence mcmv immunity, we designed an efficient, sens ... | 2003 | 12951218 |
| specific history of heterologous virus infections determines anti-viral immunity and immunopathology in the lung. | having previously shown that previous immunity to one virus can influence the host response to a subsequent unrelated virus, we questioned whether the outcome to a given virus infection would be altered in similar or different ways by previous immunity to different viruses, and whether immunity to a given virus would have similar effects on all subsequent infections. in mouse models of respiratory viral infections, immunity to lymphocytic choriomeningitis virus (lcmv), murine cytomegalovirus (mc ... | 2003 | 14507643 |
| calling in the troops: regulation of inflammatory cell trafficking through innate cytokine/chemokine networks. | the recruitment of immune effector cells to localized sites of infection is crucial for the effective delivery of innate immune mechanisms. under the conditions of infections with murine cytomegalovirus (mcmv), a herpesvirus with pathogenic potential, early immune functions are essential in the control of virus replication and virus-induced pathology. our studies have demonstrated that the chemokine macrophage inflammatory protein-1alpha (mip-1alpha) is critical for natural killer (nk) cell infl ... | 2003 | 14583145 |
| murine cytomegalovirus m157 mutation and variation leads to immune evasion of natural killer cells. | effective natural killer (nk) cell recognition of murine cytomegalovirus (mcmv)-infected cells depends on binding of the ly49h nk cell activation receptor to the m157 viral glycoprotein. here we addressed the immunological consequences of variation in m157 sequence and function. we found that most strains of mcmv possess forms of m157 that evade ly49h-dependent nk cell activation. importantly, repeated passage of mcmv through resistant ly49h+ mice resulted in the rapid emergence of m157 mutants ... | 2003 | 14597723 |
| improved detection and quantification of mouse cytomegalovirus by real-time pcr. | during latent cytomegalovirus (cmv) infection, viral presence cannot be detected by plaque assay. therefore, we assessed the applicability of real-time pcr for temporal determination of virus dissemination in two different mouse strains. eight-week-old balb/c and c57bl/6j mice were infected with mouse cmv (mcmv) and sacrificed at 1, 2, 4, 6, 14 and 28 days post infection. real-time pcr was used to determine mcmv copy number in the heart, bone marrow cells, aorta and blood. in lung, liver, saliva ... | 2003 | 14609626 |
| murine cytomegalovirus paralyzes macrophages by blocking ifn gamma-induced promoter assembly. | macrophages (m phi) are activated by ifn gamma and are important cellular targets for infection by human and murine cytomegalovirus (mcmv), making it advantageous for cmvs to block ifn gamma-induced m phi differentiation. we found that mcmv infection inhibited ifn gamma regulation of many genes in m phi. mcmv infection blocked ifn gamma responses at the level of transcription without blocking janus kinase/signal transducer and activator of transcription pathway activation and targeted ifn respon ... | 2003 | 14614150 |
| pathogenesis of murine cytomegalovirus infection. | infection of mice with murine cytomegalovirus (mcmv) is an established model for studying human cytomegalovirus (hcmv) infection. similarly to hcmv infection, pathological changes and disease manifestations during mcmv infection are mainly dependent on the immune status of the mouse host. this review focuses mainly on the pathogenesis of mcmv infection in immunocompetent and immunodeficient and/or immature mice and discusses the principles of immunosurveillance of infection and the mechanisms by ... | 2003 | 14623023 |
| efficacy of methylenecyclopropane analogs of nucleosides against herpesvirus replication in vitro. | we have reported previously that purine methylenecyclopropane analogs are potent agents against cytomegaloviruses. in an attempt to extend the activity of these compounds, the 2-amino-6-cyclopropylaminopurine analog, qyl-1064, was selected for further study by modifying the purine 6 substituent. a total of 22 analogs were tested against herpes simplex virus types 1 and 2 (hsv-1, hsv-2), varicella zoster virus (vzv), human cytomegalovirus (hcmv), murine cytomegalovirus (mcmv), epstein-barr virus ... | 2003 | 14714760 |
| synthesis and antiviral activity of (z)- and (e)-2,2-[bis(hydroxymethyl)cyclopropylidene]methylpurines and -pyrimidines: second-generation methylenecyclopropane analogues of nucleosides. | the second generation of methylenecyclopropane analogues of nucleosides 5a-5i and 6a-6i was synthesized and evaluated for antiviral activity. the 2,2-bis(hydroxymethyl)methylenecyclopropane (11) was converted to dibromo derivative 7 via acetate 12. alkylation-elimination of adenine (16) with 7 afforded the z/e mixture of acetates 17 + 18, which was deacetylated to give analogues 5a and 6a separated by chromatography. a similar reaction with 2-amino-6-chloropurine (19) afforded acetates 20 + 21 a ... | 2004 | 14736238 |
| cytomegalovirus infection aggravates atherogenesis in apoe knockout mice by both local and systemic immune activation. | since the 1970s, cytomegalovirus (cmv) infection has been associated with atherosclerotic disease. however, the exact contribution of the virus remains uncertain. in this article we describe both a direct and indirect immune-mediated effect of the virus on the disease process. eight-week-old apolipoprotein e (apoe) knockout mice were infected with mouse cmv (mcmv) or mock injected, and they were sacrificed at 2 and 20 weeks post-injection (p.i.) to study atherosclerosis, vascular wall ifngamma a ... | 2004 | 14738889 |
| expansion of protective cd8+ t-cell responses driven by recombinant cytomegaloviruses. | cd8(+) t cells are critical for the control of many persistent viral infections, such as human immunodeficiency virus, hepatitis c virus, epstein-barr virus, and cytomegalovirus (cmv). in most infections, large cd8(+)-t-cell populations are induced early but then contract and are maintained thereafter at lower levels. in contrast, cd8(+) t cells specific for murine cmv (mcmv) have been shown to gradually accumulate after resolution of primary infection. this unique behavior is restricted to cert ... | 2004 | 14963122 |
| coordinate expression of cytokines and chemokines by nk cells during murine cytomegalovirus infection. | cytokines and chemokines activate and direct effector cells during infection. we previously identified a functional group of five cytokines and chemokines, namely, ifn-gamma, activation-induced t cell-derived and chemokine-related cytokine/lymphotactin, macrophage-inflammatory protein 1alpha, macrophage-inflammatory protein 1beta, and rantes, coexpressed in individual activated nk cells, cd8(+) t cells, and cd4(+) th1 cells in vitro and during in vivo infections. however, the stimuli during infe ... | 2004 | 14978118 |
| the ribonucleotide reductase r1 homolog of murine cytomegalovirus is not a functional enzyme subunit but is required for pathogenesis. | ribonucleotide reductase (rnr) is the key enzyme in the biosynthesis of deoxyribonucleotides. alpha- and gammaherpesviruses express a functional enzyme, since they code for both the r1 and the r2 subunits. by contrast, betaherpesviruses contain an open reading frame (orf) with homology to r1, but an orf for r2 is absent, suggesting that they do not express a functional rnr. the m45 protein of murine cytomegalovirus (mcmv) exhibits the sequence features of a class ia rnr r1 subunit but lacks cert ... | 2004 | 15047841 |
| type i ifn-beta gene therapy suppresses cardiac cd8+ t-cell infiltration during autoimmune myocarditis. | gene therapy using dna encoding type i ifn subtypes ifna6, ifna9 and ifnb suppresses murine cytomegalovirus (mcmv)-myocarditis, a predominantly cell-mediated disease in balb/c mice. cd8(+) t cells are the principal cell type within the inflamed myocardium. as such, we investigated the effects of ifn subtype treatment on this t-cell subset and other cell types in the cardiac infiltrate. in the acute phase of disease, ifna6 and ifna9 treatments significantly reduced the number of cd8(+) t cells wi ... | 2004 | 15061762 |
| does toll-like receptor 3 play a biological role in virus infections? | the toll-like receptor (tlr) family functions to recognize conserved microbial and viral structures with the purpose of activating signal pathways to instigate immune responses against infections by these organisms. for example, in vitro studies reveal that the tlr3 ligand is a double-stranded rna (dsrna), a product of viral infections. from this observation, it has been proposed that tlr3 is likely an important first signal for virus infections. we approached this issue by investigating the rol ... | 2004 | 15110521 |
| murine cytomegalovirus interference with antigen presentation has little effect on the size or the effector memory phenotype of the cd8 t cell response. | as with most herpesviruses, cmvs encode viral genes that inhibit ag presentation to cd8 t cells (viprs). vipr function has been assumed to be essential for cmv to establish its characteristic lifetime infection of its host. we compared infection of c57bl/6 mice with wild-type murine cmv (mcmv) and a virus lacking each of mcmv's three known viprs: m4, m6, and m152. during acute infection, there was very little difference between the two viruses with respect to the kinetics of viral replication an ... | 2004 | 15153514 |
| escape of mutant double-stranded dna virus from innate immune control. | as innate immune system components, natural killer (nk) cells respond rapidly to infections and effectively control replication of pathogens, including murine cytomegalovirus (mcmv), a double-stranded dna beta-herpesvirus. in the absence of nk cell control, mcmv infection results in early mortality due to uncontrolled viral replication. however, here we show that even in the face of initial nk cell control, there is late recrudescence of disease and mortality in immunodeficient mice due to the o ... | 2004 | 15189739 |
| murine cytomegalovirus with a transposon insertional mutation at open reading frame m155 is deficient in growth and virulence in mice. | a pool of murine cytomegalovirus (mcmv) mutants was previously generated by using a tn3-based transposon mutagenesis approach (x. zhan, m. lee, j. xiao, and f. liu, j. virol. 74:7411-7421, 2000). in this study, one of the mcmv mutants, rvm155, which contained the transposon insertion in open reading frame m155, was characterized in vitro for its replication in tissue culture and in vivo for its growth and virulence in immunodeficient scid mice. compared to the wild-type strain and a rescued viru ... | 2004 | 15194765 |
| the r131 gene of rat cytomegalovirus encodes a proinflammatory cc chemokine homolog which is essential for the production of infectious virus in the salivary glands. | rat cytomegalovirus (rcmv) possesses two adjacent genes, r131 and r129, which have the potential to encode cc chemokine homologs. interestingly, the amino acid sequences encoded by both genes show similarity to the sequence of the murine cmv (mcmv) mck-2 protein, which is encoded by the m131/129 gene. in order to study the significance of the r131 gene in the pathogenesis of rcmv infection, we generated two different virus strains in which the r131 open reading frame is disrupted. replication of ... | 2004 | 15215683 |
| gain of virulence caused by loss of a gene in murine cytomegalovirus. | mouse strains are either resistant or susceptible to murine cytomegalovirus (mcmv). resistance is determined by the cmv1(r) (ly49h) gene, which encodes the ly49h nk cell activation receptor. the protein encoded by the m157 gene of mcmv has been defined as a ligand for ly49h. to find out whether the m157 protein is the only ly49h ligand encoded by mcmv, we constructed the m157 deletion mutant and a revertant virus. viruses were tested for susceptibility to nk cell control in ly49h+ and ly49h- mou ... | 2004 | 15220428 |
| photochemical treatment of platelet concentrates with amotosalen hydrochloride and ultraviolet a light inactivates free and latent cytomegalovirus in a murine transfusion model. | a photochemical treatment (pct) process utilizing amotosalen hydrochloride and long wavelength uva light has been developed to inactivate pathogens in plts. this study investigated the effects of amotosalen/uva treatment on free and latent murine cmv (mcmv) in plt preparations using a murine model of transfusion-transmitted cmv (tt-cmv). | 2004 | 15265119 |
| oral treatment of murine cytomegalovirus infections with ether lipid esters of cidofovir. | to improve the oral bioavailability of cidofovir (cdv), a series of ether lipid ester prodrugs were synthesized and evaluated for activity against murine cytomegalovirus (mcmv) infection. four of these analogs, hexadecyloxypropyl (hdp)-cdv, octadecyloxyethyl (ode)-cdv, oleyloxyethyl (ole)-cdv, and oleyloxypropyl (olp)-cdv, were found to have greater activity than cdv against human cmv and mcmv in vitro. the efficacy of oral treatment with these compounds against mcmv infections in balb/c mice wa ... | 2004 | 15328119 |
| the cytomegalovirus m155 gene product subverts natural killer cell antiviral protection by disruption of h60-nkg2d interactions. | natural killer (nk) cells are an important early mediator of host immunity to murine cytomegalovirus (mcmv) infection. however, mcmv has evolved mechanisms to elude recognition and clearance by nk cells. we have identified an mcmv immune evasion protein that impairs nkg2d-mediated nk cell antiviral activity. infection of balb/c 3t3 cells with the smith strain of mcmv resulted in strong down-regulation of h60, a high affinity ligand for nkg2d, from the surface of virus-infected cells. the mcmv m1 ... | 2004 | 15477345 |
| genetic analysis of cytomegalovirus by shuttle mutagenesis. | the genomes of herpesviridae family members are among the largest of all viruses and therefore present a formidable challenge in understanding the roles of every gene in replication or pathogenesis. for example, murine cytomegalovirus (mcmv) has a genome of 230 kb that encodes more than 170 genes, many of which have unknown functions. many techniques for the genetic analysis of a herpesvirus have been developed over the past two decades. one such procedure involves the use of a shuttle mutagenes ... | 2005 | 15507721 |
| susceptibility to murine cytomegalovirus retinitis during progression of maids: correlation with intraocular levels of tumor necrosis factor-alpha and interferon-gamma. | to correlate tumor necrosis factor-alpha (tnf-alpha) and interferon-gamma (ifn-gamma) synthesis with histopathologic disease and virus replication within murine cytomegalovirus (mcmv)-infected eyes during progression of murine acquired immunodeficiency syndrome (maids). | 2004 | 15512964 |
| cmv1-independent antiviral role of nk cells revealed in murine cytomegalovirus-infected new zealand white mice. | ly49h(+) nk cells play a critical role in innate antiviral immune responses to murine cmv (mcmv). ly49h(b6) recognition of mcmv-encoded m157 on infected cells activates natural killing required for host resistance. we show that mab 3d10 (anti-ly49h) recognizes comparable subsets of nk cells from new zealand white (nzw), new zealand black (nzb), and c57bl/6 spleens. however, virus levels in the spleens of mcmv-infected nzw and nzb mice differed greatly. we found that mcmv replication in infected ... | 2004 | 15528370 |
| identification of a mouse cytomegalovirus gene selectively targeting cd86 expression on antigen-presenting cells. | we and others have shown that infection of dendritic cells with murine cytomegalovirus (mcmv) leads to severe functional impairment of these antigen-presenting cells (d. m. andrews, c. e. andoniou, f. granucci, p. ricciardi-castagnoli, and m. a. degli-esposti, nat. immunol. 2:1077-1084, 2001; s. mathys, t. schroeder, j. ellwart, u. h. koszinowski, m. messerle, and u. just, j. infect. dis. 187:988-999, 2003). phenotypically, reduced surface expression of costimulatory molecules and major histocom ... | 2004 | 15542658 |
| interleukin-2 immunotherapy and aids-related cytomegalovirus retinitis. | cytokines are small proteins produced by t lymphocytes that mediate immune responses. those produced by the cd4+ th1 subset induce cell-mediated immunity, whereas those produced by the cd4+ th2 subset are more efficient at stimulating immunoglobulin production. the goal of cytokine immunotherapy is prevention or reduction of disease progression through stimulation of cell-mediated immunity (i.e., immune reconstitution) by administration of an exogenous th1 cytokine such as interleukin-2 (il-2). ... | 2004 | 15544454 |
| oral activity of a methylenecyclopropane analog, cyclopropavir, in animal models for cytomegalovirus infections. | we reported previously that purine 2-(hydroxymethyl)methylenecyclopropane analogs have good activity against cytomegalovirus infection. a second-generation analog, (z)-9-[[2,2-bis-(hydroxymethyl)cyclopropylidene]methyl]guanine (zsm-i-62, cyclopropavir [cpv]), has particularly good activity against murine and human cytomegaloviruses (mcmv and hcmv) in vitro. to determine the oral activity of this compound in vivo, balb/c or severe combined immunodeficient (scid) mice infected with mcmv and two mo ... | 2004 | 15561852 |
| systemic priming-boosting immunization with a trivalent plasmid dna and inactivated murine cytomegalovirus (mcmv) vaccine provides long-term protection against viral replication following systemic or mucosal mcmv challenge. | we previously demonstrated that vaccination of balb/c mice with a pool of 13 plasmid dnas (pdnas) expressing murine cytomegalovirus (mcmv) genes followed by formalin-inactivated mcmv (fi-mcmv) resulted in complete protection against viral replication in the spleen and salivary glands following sublethal intraperitoneal (i.p.) challenge. here, we found that following intranasal (i.n.) challenge, titers of virus in the lungs of the immunized mice were reduced approximately 1,000-fold relative to t ... | 2005 | 15596812 |
| cell-mediated cytotoxicity of murine cytomegalovirus-infected target cells allows for release of residual infectious virus. | although cell-mediated cytotoxicity effectively kills target virus-infected cells, no careful consideration has been given to the fate of infectious progeny virus contained within target cells following the cytolytic event. to address this issue with respect to murine cytomegalovirus (mcmv) pathogenesis, we developed a rapid semiquantitative assay for infectious mcmv based on expression of beta-galactosidase using a lacz-expressing recombinant mcmv. simultaneous use of this assay in combination ... | 2004 | 15614430 |
| (z)- and (e)-[2-fluoro-2-(hydroxymethyl)cyclopropylidene]methylpurines and -pyrimidines, a new class of methylenecyclopropane analogues of nucleosides: synthesis and antiviral activity. | the z- and e-isomers of fluoromethylenecyclopropane analogues 11a-d and 12a-d were synthesized, and their antiviral activities were evaluated. the purine (z,e)-methylenecyclopropane carboxylates 13 and 24 were selectively fluorinated using lithium diisopropylamide, licl, and n-fluorobenzenesulfonimide to give (z,e)-fluoroesters 22 and 25. reduction with libh(4) or diisobutylaluminum hydride gave after chromatographic separation z-isomers 11a and 11e and e-isomers 12a and 12e. the o-demethylation ... | 2004 | 15615545 |
| intranasal immunization with a replication-deficient adenovirus vector expressing glycoprotein h of murine cytomegalovirus induces mucosal and systemic immunity. | a vaccine vector, designated adv-gh, was constructed by inserting the complete open reading frame of mcmv gh under control of the human cmv ie-1 promoter into the e-1 region of a replication-deficient adenovirus 5. in vitro infection of qb1-293 cells and mouse embryo cells with adv-gh resulted in expression of mcmv gh detected by ifa. immunization of balb/c mice with adv-gh (1 x 10(7) pfu) given by the intranasal route induced a humoral response with antibody detected in serum of 100% of vaccine ... | 2005 | 15620472 |
| ocular reactivation of mcmv after immunosuppression of latently infected balb/c mice. | the purpose of this study was to identify the site(s) of mcmv latency and reactivation in the eye. | 2005 | 15623781 |
| nk cell activation through the nkg2d ligand mult-1 is selectively prevented by the glycoprotein encoded by mouse cytomegalovirus gene m145. | the nk cell-activating receptor nkg2d interacts with three different cellular ligands, all of which are regulated by mouse cytomegalovirus (mcmv). we set out to define the viral gene product regulating murine ul16-binding protein-like transcript (mult)-1, a newly described nkg2d ligand. we show that mcmv infection strongly induces mult-1 gene expression, but surface expression of this glycoprotein is nevertheless completely abolished by the virus. screening a panel of mcmv deletion mutants defin ... | 2005 | 15642742 |
| selective down-regulation of the nkg2d ligand h60 by mouse cytomegalovirus m155 glycoprotein. | both human and mouse cytomegaloviruses (cmvs) encode proteins that inhibit the activation of nk cells by down-regulating cellular ligands for the activating nk cell receptor nkg2d. up to now, three ligands for the nkg2d receptor, named rae-1, h60, and mult-1, have been identified in mice. the resistance of mouse strains to murine cmv (mcmv) infection is determined by their ability to generate an effective nk cell response. the mcmv gene m152, a member of the m145 gene family, down-regulates the ... | 2005 | 15709011 |