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human cytomegalovirus. preface. 200818637496
functional roles of the human cytomegalovirus essential ie86 protein.the ie86 protein of human cytomegalovirus (hcmv) is unique among viral and cellular proteins because it negatively autoregulates its own expression, activates the viral early and late promoters, and both activates and inhibits cellular promoters. it promotes cell cycle progression from go/g1 to g1/s and arrests cell cycle progression at the g1/s interface or at g2/m. the ie86 protein is essential because it creates a cellular environment favorable for viral replication. the multiple functions of ...200818637504
human cytomegalovirus modulation of signal transduction.an upregulation of cellular signaling pathways is observed in multiple cell types upon human cytomegalovirus (hcmv) infection, suggesting that a global feature of hcmv infection is the activation of the host cell. hcmv initiates and maintains cellular signaling through a multitiered process that is dependent on a series of events: (1) the viral glycoprotein ligand interacts with its cognate receptor, (2) cellular enzymes and viral tegument proteins present in the incoming virion are released and ...200818637508
subversion of cell cycle regulatory pathways.human cytomegalovirus (hcmv) has evolved numerous strategies to commandeer the host cell for producing viral progeny. the virus manipulates host cell cycle pathways from the early stages of infection to stimulate viral dna replication at the expense of cellular dna synthesis. at the same time, cell cycle checkpoints are by-passed, preventing apoptosis and allowing sufficient time for the assembly of infectious virus.200818637510
aspects of human cytomegalovirus latency and reactivation.primary infection of healthy individuals with human cytomegalovirus (hcmv) is usually asymptomatic and results in the establishment of a lifelong latent infection of the host. although no overt hcmv disease is observed in healthy carriers, due to effective immune control, severe clinical symptoms associated with hcmv reactivation are observed in immunocompromised transplant patients and hiv sufferers. work from a number of laboratories has identified the myeloid lineage as one important site for ...200818637513
cytomegalovirus vaccine development.although infection with human cytomegalovirus (hcmv) is ubiquitous and usually asymptomatic, there are individuals at high risk for serious hcmv disease. these include solid organ and hematopoietic stem cell (hsc) transplant patients, individuals with hiv infection, and the fetus. since immunity to hcmv ameliorates the severity of disease, there have been efforts made for over 30 years to develop vaccines for use in these high-risk settings. however, in spite of these efforts, no hcmv vaccine ap ...200818637516
mechanisms of cytomegalovirus-accelerated vascular disease: induction of paracrine factors that promote angiogenesis and wound healing.human cytomegalovirus (hcmv) is associated with the acceleration of a number of vascular diseases such as atherosclerosis, restenosis, and transplant vascular sclerosis (tvs). all of these diseases are the result of either mechanical or immune-mediated injury followed by inflammation and subsequent smooth muscle cell (smc) migration from the vessel media to the intima and proliferation that culminates in vessel narrowing. a number of epidemiological and animal studies have demonstrated that cmv ...200818637518
manifestations of human cytomegalovirus infection: proposed mechanisms of acute and chronic disease.infections with human cytomegalovirus (hcmv) are a major cause of morbidity and mortality in humans with acquired or developmental deficits in innate and adaptive immunity. in the normal immunocompetent host, symptoms rarely accompany acute infections, although prolonged virus shedding is frequent. virus persistence is established in all infected individuals and appears to be maintained by both a chronic productive infections as well as latency with restricted viral gene expression. the contribu ...200818637519
dynamic histone h3 acetylation and methylation at human cytomegalovirus promoters during replication in fibroblasts.human cytomegalovirus dna is packaged in virions without histones but associates with histones upon reaching the nucleus of an infected cell. since transcription is modulated by the interplay of histone modifications, we used chromatin immunoprecipitation to detect acetylation and methylation of histone h3 at viral promoters at different times during the viral replication cycle. histone h3 at immediate-early promoters is acetylated at the start of infection, while it is initially methylated at e ...200818653451
in vivo competence of murine cytomegalovirus under the control of the human cytomegalovirus major immediate-early enhancer in the establishment of latency and reactivation.the human cytomegalovirus (hcmv) major immediate-early enhancer has been postulated to play a pivotal role in the control of latency and reactivation. however, the absence of an animal model has obstructed a direct test of this hypothesis. here we report on the establishment of an in vivo, experimentally tractable system for quantitatively investigating physiological functions of the hcmv enhancer. using a neonate balb/c mouse model, we show that a chimeric murine cmv under the control of the hc ...200818684819
human cytomegalovirus ul18 utilizes us6 for evading the nk and t-cell responses.human cytomegalovirus (hcmv) us6 glycoprotein inhibits tap function, resulting in down-regulation of mhc class i molecules at the cell surface. cells lacking mhc class i molecules are susceptible to nk cell lysis. hcmv expresses ul18, a mhc class i homolog that functions as a surrogate to prevent host cell lysis. despite a high level of sequence and structural homology between ul18 and mhc class i molecules, surface expression of mhc class i, but not ul18, is down regulated by us6. here, we desc ...200818688275
incidence of human herpes virus-6 and human cytomegalovirus infections in donated bone marrow and umbilical cord blood hematopoietic stem cells.this study examined the incidence of human herpes virus-6 (hhv-6) and human cytomegalovirus (hcmv) infections that are potentially transmitted to haematopoietic stem cells (hsc) transplant recipients via bone marrow (bm) or umbilical cord blood (ucb). bone marrow progenitor cells were collected from 30 allogenic bm donors. ucb hsc were collected from 34 subjects. the extracted dna was then processed using nested polymerase chain reaction (npcr) technique. hcmv and hhv-6 serological status were d ...200818695326
maribavir: a novel antiviral agent with activity against cytomegalovirus.to review the pharmacology, pharmacokinetics, efficacy, and safety of maribavir, a novel antiviral agent in the benzimidazole drug class.200818698013
platelet-derived growth factor-alpha receptor activation is required for human cytomegalovirus infection.human cytomegalovirus (hcmv) is a ubiquitous human herpesvirus that can cause life-threatening disease in the fetus and the immunocompromised host. upon attachment to the cell, the virus induces robust inflammatory, interferon- and growth-factor-like signalling. the mechanisms facilitating viral entry and gene expression are not clearly understood. here we show that platelet-derived growth factor-alpha receptor (pdgfr-alpha) is specifically phosphorylated by both laboratory and clinical isolates ...200818701889
synthesis and characterization of novel quinazoline type inhibitors for mutant and wild-type egfr and rick kinases.the development of selective protein kinase inhibitors has become an important area of drug discovery for the treatment of different diseases. we report the synthesis and characterization of a series of novel quinazoline derivatives against three therapeutically important and pharmacologically related kinases: 1) epidermal growth factor receptor (egfr; wild type and mutant) in the field of cancer, 2) receptor-interacting caspase-like apoptosis-regulatory kinase (rick) in the field of inflammatio ...200818702009
anchor-based fluorescent amplicon generation assays (flag) for real-time measurement of human cytomegalovirus, epstein-barr virus, and varicella-zoster virus viral loads.monitoring the human cytomegalovirus (hcmv), epstein-barr virus (ebv), or varicella-zoster virus (vzv) viral load is an important factor in the management of immunosuppressed patients, such as recipients of solid-organ or bone marrow transplants. the advent of real-time pcr technologies has prompted the widespread development of quantitative pcr assays for the detection of viral loads and other diagnostic purposes.200818703767
sel1l nucleates a protein complex required for dislocation of misfolded glycoproteins.membrane and secretory proteins that fail to pass quality control in the endoplasmic reticulum are discharged into the cytosol and degraded by the proteasome. many of the mammalian components involved in this process remain to be identified. we performed a biochemical search for proteins that interact with sel1l, a protein that is part of the mammalian hrd1 ligase complex and involved in substrate recognition. sel1l is crucial for dislocation of class i major histocompatibility complex heavy cha ...200818711132
genetic linkage among human cytomegalovirus glycoprotein n (gn) and go genes, with evidence for recombination from congenitally and post-natally infected japanese infants.investigation of sequence polymorphisms in the glycoprotein n (gn; gp4273), go (gp4274) and gh (gp4275) genes of human cytomegalovirus (hcmv) strains collected from 63 japanese children revealed that their go genotype distribution differed slightly from that of caucasian populations and that there was a significant linkage between the gn and go genotypes. linkage of these genotypes in strains obtained from caucasian populations has been reported, so our similar findings in japanese infants are c ...200818753237
germline v-genes sculpt the binding site of a family of antibodies neutralizing human cytomegalovirus.immunoglobulin genes are generated somatically through specialized mechanisms resulting in a vast repertoire of antigen-binding sites. despite the stochastic nature of these processes, the v-genes that encode most of the antigen-combining site are under positive evolutionary selection, raising the possibility that v-genes have been selected to encode key structural features of binding sites of protective antibodies against certain pathogens. human, neutralizing antibodies to human cytomegaloviru ...200818772881
internal deletions of ie2 86 and loss of the late ie2 60 and ie2 40 proteins encoded by human cytomegalovirus affect the levels of ul84 protein but not the amount of ul84 mrna or the loading and distribution of the mrna on polysomes.the major immediate-early (ie) region of human cytomegalovirus encodes two ie proteins, ie1 72 and ie2 86, that are translated from alternatively spliced transcripts that differ in their 3' ends. two other proteins that correspond to the c-terminal region of ie2 86, ie2 60 and ie2 40, are expressed at late times. in this study, we used ie2 mutant viruses to examine the mechanism by which ie2 86, ie2 60, and ie2 40 affect the expression of a viral dna replication factor, ul84. deletion of amino a ...200818787008
generation of potent neutralizing human monoclonal antibodies against cytomegalovirus infection from immune b cells.human monoclonal antibodies (mabs) generated as a result of the immune response are likely to be the most effective therapeutic antibodies, particularly in the case of infectious diseases against which the immune response is protective.human cytomegalovirus (hcmv) is an ubiquitous opportunistic virus that is the most serious pathogenic agent in transplant patients. the available therapeutic armamentarium (e.g. hcmv hyperimmune globulins or antivirals) is associated with severe side effects and t ...200819014469
viruses as co-factors for the initiation or exacerbation of lung fibrosis.idiopathic pulmonary fibrosis (ipf) remains exactly that. the disease originates from an unknown cause, and little is known about the mechanisms of pathogenesis. while the disease is likely multi-factorial, evidence is accumulating to implicate viruses as co-factors (either as initiating or exacerbating agents) of fibrotic lung disease. this review summarizes the available clinical and experimental observations that form the basis for the hypothesis that viral infections may augment fibrotic res ...200819014649
analysis of the human cytomegalovirus pp65-directed t-cell response in healthy hla-a2-positive individuals.human cytomegalovirus (hcmv) is contained by t-lymphocyte responses focused towards the major tegument protein pp65. to systematically identify t-cell epitopes, we applied the following strategy: 441 overlapping 15mer peptides spanning the entire hcmv pp65 antigen in 1-aa steps were screened in enzyme-linked immunospot (elispot) assays for interferon gamma (ifn-gamma) secretion by peripheral blood mononuclear cells (pbmcs) from nine healthy hcmv-seropositive subjects expressing human leukocyte a ...200818953722
the magnitude of interferon-gamma responses to human cytomegalovirus is predictive for hiv-1 disease progression.human cytomegalovirus (hcmv) infection has been strongly associated to hiv-1 progression. we have investigated whether the magnitude of the overall peripheral blood mononuclear cell responses to hcmv stimulation correlated with hiv-1 progression.200818989229
human cytomegalovirus impairs the function of plasmacytoid dendritic cells in lymphoid organs.human dendritic cells (dcs) are the main antigen presenting cells (apc) and can be divided into two main populations, myeloid and plasmacytoid dcs (pdcs), the latter being the main producers of type i interferon. the vast majority of pdcs can be found in lymphoid organs, where the main pool of all immune cells is located, but a minority of pdcs also circulate in peripheral blood. human cytomegalovirus (hcmv) employs multiple mechanisms to evade the immune system. in this study, we could show tha ...200818941519
detection of human cytomegalovirus in dental plaque from individual periodontal sites by real-time polymerase chain reaction.the aim was to evaluate three primer-probe sets and real-time polymerase chain reaction (pcr) for the detection of human cytomegalovirus (hcmv) in dental plaque from individual periodontal sites.200818805716
induction of pluripotent protective immunity following immunisation with a chimeric vaccine against human cytomegalovirus.based on the life-time cost to the health care system, the institute of medicine has assigned the highest priority for a vaccine to control human cytomegalovirus (hcmv) disease in transplant patients and new born babies. in spite of numerous attempts successful licensure of a hcmv vaccine formulation remains elusive. here we have developed a novel chimeric vaccine strategy based on a replication-deficient adenovirus which encodes the extracellular domain of gb protein and multiple hla class i & ...200818806877
comparison of antigenemia assay and semiquantitative polymerase chain reaction test for monitoring active cytomegalovirus infection in allogeneic hematopoietic cell transplant recipients.we sought to compare the antigenemia assay and in-house semiquantitative polymerase chain reaction to monitor human cytomegalovirus infection after transplant in hematopoietic cell transplant recipients.200818816243
[infections in immunosuppressed patients].molecular biology techniques represent a major advance in the microbiologic diagnosis of infectious diseases, since these methods are able to detect etiological microorganisms with high sensitivity. moreover, these procedures can also establish prognostic and therapeutic efficacy markers with a sufficiently short turnaround time for the results to have a real impact on the clinical management of immunosuppressed patients. however, these techniques still have substantial limitations that should b ...200819195448
detection of herpesviruses and periodontal pathogens in subgingival plaque of patients with chronic periodontitis, generalized aggressive periodontitis, or gingivitis.herpesviruses may be related to the etiology of aggressive periodontitis (agp) and chronic periodontitis (cp) by triggering periodontal destruction or by increasing the risk for bacterial infection. this case-control study evaluated the presence of herpes simplex virus type i (hsv-1), epstein-barr virus type i (ebv-1), human cytomegalovirus (hcmv), aggregatibacter actinomycetemcomitans (previously actinobacillus actinomycetemcomitans), porphyromonas gingivalis, prevotella intermedia, and tannere ...200819053922
efficient replication of rhesus cytomegalovirus variants in multiple rhesus and human cell types.rhesus cytomegalovirus infection of rhesus macaques has emerged as a model for human cytomegalovirus pathogenesis. the ul128-ul131 locus of the human virus is a primary determinant for viral entry into epithelial cells, an important cell type during cytomegalovirus infection. rhesus cytomegalovirus strain 68-1 spreads slowly when grown in cultured rhesus epithelial cells, and it does not code for orfs corresponding to ul128 and the second exon of ul130. we repaired the ul128-ul131 locus of strai ...200819064925
[association of post transplantation diabetes mellitus to active human cytomegalovirus infection and preoperative hepatitis b virus infection: analysis of 75 cases].to investigate the relationship of post transplantation diabetes mellitus (ptdm) to active human cytomegalovirus (hcmv) infection and to preoperative hepatitis b virus (hbv) infection respectively.200819080434
[polymorphism analysis of human cytomegalovirus ul150 gene in low passage clinical isolates].to investigate the polymorphism of human cytomegalovirus ul150 gene in low passage clinical isolates and try to study the relationship between the polymorphism and different pathogenesis of congenital hcmv infection.200819105344
hcmv il-10 suppresses cytokine expression in monocytes through inhibition of nuclear factor-kappab.modulation of host immune responses is a common strategy for promoting virus persistence and avoiding clearance. human cytomegalovirus (hcmv) is known to encode numerous immunomodulatory genes, including a homolog of the cytokine human interleukin-10 (hil-10). while having limited sequence homology to hil-10, cytomegalovirus il-10 (cmvil-10) shares many functional characteristics with the human cytokine and acts as a potent suppressor of the inflammatory immune response. the mechanism by which h ...200819115937
new cell-based indicator assays for the detection of human cytomegalovirus infection and screening of inhibitors of viral immediate-early 2 protein activity.expression of early (e) genes of human cytomegalovirus (hcmv) is stimulated cooperatively by the activities of host cell transcription factors and the viral immediate-early 2 (ie2) protein. taking advantage of the ie2-dependent inducibility of e gene promoters, in this study, we generated cell-based assays in which the expression of the enhanced green fluorescence protein (egfp) reporter gene was driven by the ul54 or ul112/113 e promoters.200819120629
optimization of human cytomegalovirus lightcycler real-time pcr.real-time pcr has been widely considered as a powerful tool for the evaluation of human cytomegalovirus (cmv) dna kinetics. successful pcr relies on optimization, which is an extremely demanding procedure. nevertheless, certain values could be optimal for most primers in use.200819745514
expression of gdnf transgene in astrocytes improves cognitive deficits in aged rats.glial cell line-derived neurotrophic factor (gdnf) was assayed for its neurotrophic effects against the neuronal atrophy that causes cognitive deficits in old age. aged fisher 344 rats with impairment in the morris water maze received intrahippocampal injections at the dorsal ca1 area of either a lentiviral vector encoding human gdnf or the same vector encoding human green fluorescent protein as a control. recombinant lentiviral vectors constructed with human cytomegalovirus promotor and pseudot ...200817399854
the late promoter of the human cytomegalovirus viral dna polymerase processivity factor has an impact on delayed early and late viral gene products but not on viral dna synthesis.transcription of the dna polymerase processivity factor gene (ul44) of human cytomegalovirus initiates at three distinct start sites, which are differentially regulated during productive infection. two of these start sites, the distal and proximal sites, are active at early times, and the middle start site is active at only late times after infection (f. leach and e. s. mocarski, j. virol. 63:1783-1791, 1989). compared to the wild type, ul44 gene expression was lower for recombinant viruses with ...200717409154
an intrastrain variation of a 189-bp repeat region in the human cytomegalovirus replication origin.a 189-bp repeat has been reported previously to be present in the replication origin (ori) of human cytomegalovirus (hcmv) towne strain and to contain essential and supporting sequences (chen et al., arch. virol. 141, 13301 (1996)). in this study, clones of hcmv strain towne were isolated and analyzed for the copy number of the 189-bp repeat within its ori (orilyt). southern blot analysis revealed that out of 14 clones, two contained a dimer, two contained a tetramer, and the remaining contained ...200717432940
pathogenesis and antibody response to a cytomegalovirus infection in newborn rats.the present study described the kinetics of rat cytomegalovirus (rcmv) infection in newborn rats by monitoring infectious virus and viral antigens in various organs, viral dna in the blood (dnaemia) and antibody response. these parameters were evaluated quantitatively using double-antibody sandwich elisa (das-elisa), real-time pcr, indirect elisa and virus infectivity assay. for the first time das-elisa was used for detection of rcmv antigen directly from organ samples. the relationships between ...200717432941
functional role of mglur1 and mglur4 in pilocarpine-induced temporal lobe epilepsy.altered expression and distribution of neurotransmitter receptors, including metabotropic glutamate receptors (mglurs), constitute key aspects in epileptogenesis, impaired hippocampal excitability and neuronal degeneration. mglur1 mediates predominantly excitatory effects, whereas mglur4 acts as inhibitory presynaptic receptor. increased hippocampal expression of mglur1 and mglur4 has been observed in human temporal lobe epilepsy (tle). in this study, we address whether genetic mglur1 upregulati ...200717446080
[human cytomegalovirus infection]. 200717455606
[mechanism of drug-resistance in human cytomegalovirus]. 200717455666
exploiting the yeast l-a viral capsid for the in vivo assembly of chimeric vlps as platform in vaccine development and foreign protein expression.a novel expression system based on engineered variants of the yeast (saccharomyces cerevisiae) dsrna virus l-a was developed allowing the in vivo assembly of chimeric virus-like particles (vlps) as a unique platform for a wide range of applications. we show that polypeptides fused to the viral capsid protein gag self-assemble into isometric vlp chimeras carrying their cargo inside the capsid, thereby not only effectively preventing proteolytic degradation in the host cell cytosol, but also allow ...200717476337
synthesis and biological evaluation of some alpha-[6-(1'-carbamoylalkylthio)-1 h-pyrazolo[3,4-d]pyrimidin-4-yl]thioalkylcarboxamide acyclonucleosides.the reaction of 1h-pyrazolo[3,4-d]pyrimidin-4,6-dithione 11 with compounds 12a-c produces ethyl alpha-[6-(1'-carboethoxyalkylthio)-1 h-pyrazolo[3,4-d]pyrimidin-4-yl]thioalkylates 13a-c, respectively. these heterocycles were alkylated, separately, with alkylating agents 14, 15, and 16 to afford, predominately, the n(1)-acyclic nucleosides (17-19)a-c, which were deprotected to give the desired products (20-22)a-c. all synthetic compounds were characterized on the basis of their physical and spectr ...200717479430
a prospective assessment of cytomegalovirus immune evasion gene transcription profiles in transplant patients with cytomegalovirus infection.the cytomegalovirus (cmv) immune evasion genes us3, us6, and us11 may disrupt the host immune response via downregulation of major histocompatibility complex molecules. transplant recipients with cmv infection were prospectively assessed for immune evasion gene expression.200717496536
herpesvirus latency confers symbiotic protection from bacterial infection.all humans become infected with multiple herpesviruses during childhood. after clearance of acute infection, herpesviruses enter a dormant state known as latency. latency persists for the life of the host and is presumed to be parasitic, as it leaves the individual at risk for subsequent viral reactivation and disease. here we show that herpesvirus latency also confers a surprising benefit to the host. mice latently infected with either murine gammaherpesvirus 68 or murine cytomegalovirus, which ...200717507983
cytomegalovirus destruction of focal adhesions revealed in a high-throughput western blot analysis of cellular protein expression.human cytomegalovirus (hcmv) systematically manages the expression of cellular functions, rather than exerting the global shutoff of host cell protein synthesis commonly observed with other herpesviruses during the lytic cycle. while microarray technology has provided remarkable insights into viral control of the cellular transcriptome, hcmv is known to encode multiple mechanisms for posttranscriptional and post-translation regulation of cellular gene expression. high-throughput western blotting ...200717522202
endothelial cells' activation and apoptosis induced by a subset of antibodies against human cytomegalovirus: relevance to the pathogenesis of atherosclerosis.human cytomegalovirus (hcmv) is involved in the pathogenesis of atherosclerosis. we have previously shown in patients with atherosclerosis that antibodies directed against the hcmv-derived proteins us28 and ul122 are able to induce endothelial cell damage and apoptosis of non-stressed endothelial cells through cross-rection with normally expressed surface molecules. our aim was to dissect the molecular basis of such interaction and to investigate mechanisms linking innate immunity to atheroscler ...200717534423
[correlation between mhc class i-related chain a gene *008 allele and human cytomegalovirus infection].to investigate the correlation between mhc class i-related chain a (mica) gene *008 allele and human cytomegalovirus (hcmv) infection.200717545046
vaccine strategies against human cytomegalovirus infection.human cytomegalovirus (hcmv) disease is a major cause of morbidity and mortality in neonates and immunocompromised populations, such as transplant recipients and hiv-infected patients. the development of a vaccine to prevent hcmv infection or disease has been assigned the highest priority by the us institute of medicine. although, after 30 years of intensive study, a clinically licensed vaccine is still not available, significant progress has been made in the field of hcmv vaccine development, a ...200717547509
comparison of two methods used for monitoring low-copy cytomegalovirus infection in a patient with chronic myeloid leukemia after unrelated umbilical cord blood transplantation.detection of human cytomegalovirus (cmv, hhv-5) dna in clinical specimens is considered a cornerstone in the diagnosis of hhv-5 disease. the present study compared two quantitative methods used for diagnosing cytomegalovirus infection in a 21-year-old woman with chronic myeloid leukemia after an unrelated umbilical cord blood transplantation.200717557148
human cytomegalovirus gene expression is silenced by daxx-mediated intrinsic immune defense in model latent infections established in vitro.in addition to productive lytic infections, herpesviruses such as human cytomegalovirus (hcmv) establish a reservoir of latently infected cells that permit lifelong colonization of the host. when latency is established, the viral immediate-early (ie) genes that initiate the lytic replication cycle are not expressed. hcmv ie gene expression at the start of a lytic infection is facilitated by the viral pp71 protein, which is delivered to cells by infectious viral particles. pp71 neutralizes the da ...200717596307
human cytomegalovirus glycoprotein b genotypes in brazilian mothers and their congenitally infected infants.a case-control study design was used in order to compare the distribution of human cytomegalovirus (hcmv) glycoprotein b (gb) genotypes in 48 mothers of 49 congenitally infected infants with that observed in 144 mothers of 146 uninfected infants to study genetic variation of hcmv strains and maternal-fetal transmission. congenital infection with hcmv was characterized by dna detection and virus isolation from two urine or saliva samples collected prior to the third week of life. genotyping of hc ...200717597488
recruitment of human cytomegalovirus immediate-early 2 protein onto parental viral genomes in association with nd10 in live-infected cells.the human cytomegalovirus (hcmv) immediate-early 2 (ie2) transactivator has previously been shown to form intranuclear, dot-like accumulations in association with subnuclear structures known as promyelocytic leukemia protein (pml) nuclear bodies or nd10. we recently observed that ie2 can form dot-like structures even after infection of pml knockdown cells, which lack genuine nd10. to further analyze the determinants of ie2 subnuclear localization, a recombinant hcmv expressing ie2 fused to the e ...200717626080
an importin alpha/beta-recognized bipartite nuclear localization signal mediates targeting of the human herpes simplex virus type 1 dna polymerase catalytic subunit pul30 to the nucleus.although the 1235 amino acids human herpes simplex virus type 1 (hsv-1) dna polymerase catalytic subunit, pul30, is essential for hsv-1 replication in the nucleus of host cells, little information is available regarding its nuclear import mechanism. the present study addresses this issue directly, characterizing pul30's nuclear import pathway for the first time using quantitative confocal laser scanning microscopy (clsm) on living cells, and fluorescent binding assays. in addition to a previousl ...200717640102
host immune system gene targeting by a viral mirna.virally encoded micrornas (mirnas) have recently been discovered in herpesviruses. however, their biological roles are mostly unknown. we developed an algorithm for the prediction of mirna targets and applied it to human cytomegalovirus mirnas, resulting in the identification of the major histocompatibility complex class i-related chain b (micb) gene as a top candidate target of hcmv-mir-ul112. micb is a stress-induced ligand of the natural killer (nk) cell activating receptor nkg2d and is criti ...200717641203
dislocation of an endoplasmic reticulum membrane glycoprotein involves the formation of partially dislocated ubiquitinated polypeptides.accumulation of improperly folded polypeptides in the endoplasmic reticulum (er) can trigger a stress response that leads to the export of aberrant proteins into the cytosol and their ultimate proteasomal degradation. human cytomegalovirus encodes a type i glycoprotein, us11, that binds to nascent mhc class i heavy chain molecules and causes their dislocation from the er to the cytosol where they are degraded by the proteasome. examination of us11-mediated class i degradation has identified a ho ...200717650499
a model of human cytomegalovirus infection in severe combined immunodeficient mice.animal models for the evaluation of therapies against human cytomegalovirus (hcmv) are limited due to the species-specific replication of cmv. models utilizing human fetal tissues implanted into scid mice have been used but tend to be labor intensive and require human tissues. we therefore developed a model using hcmv-infected human foreskin fibroblasts (hff) seeded onto a biodegradable gelatin matrix (gelfoam). infected hffs are then implanted subcutaneously into scid mice. we next evaluated tw ...200717658624
usefulness of interleukin-10 detection in lung transplant patients with human cytomegalovirus infection with respect to virus persistence.human cytomegalovirus (hcmv) infection in lung transplant patients induces an inflammatory response, including local production of cytokines involved in viral clearance. the aim of this study was to evaluate the potential value of monitoring interleukin (il)-10 with respect to hcmv persistence in blood and/or bronchoalveolar lavage (bal).200717667821
the s phase of the cell cycle and its perturbation by human cytomegalovirus.human cytomegalovirus (hcmv) is a complex human herpesvirus that is known to productively infect a wide range of cell types. in addition, it has been suggested to contribute to some proliferative disorders, particularly atherosclerosis. consistent with this, a number of studies have shown that hcmv profoundly affects normal cell cycle control. specifically, the virus can stimulate early entry into s phase thus ensuring adequate resources for viral dna replication. importantly, however, the virus ...200717676653
antisense transcription in the human cytomegalovirus transcriptome.human cytomegalovirus (hcmv) infections are prevalent in human populations and can cause serious diseases, especially in those with compromised or immature immune systems. the hcmv genome of 230 kb is among the largest of the herpesvirus genomes. although the entire sequence of the laboratory-adapted ad169 strain of hcmv has been available for 18 years, the precise number of viral genes is still in question. we undertook an analysis of the hcmv transcriptome as an approach to enumerate and analy ...200717686857
cytomegalovirus ul131-128 products promote gb conformational transition and gb-gh interaction during entry into endothelial cells.herpesviruses use gb and gh-gl glycoproteins to execute fusion. other virus-specific glycoproteins are required for receptor binding and fusion activation. the human cytomegalovirus (hcmv) ul131-128 proteins are essential for the infection of leukocytes, endothelial cells (ecs), and many epithelial cell lines. here we show that ul131-128 play a role in a chain of events involving gb and gh during hcmv entry into ecs. an hcmv strain bearing the wild-type (wt) ul131-128 locus exhibited a gb transi ...200717686875
serum proteomics with seldi-tof-ms in congenital human cytomegalovirus hepatitis.human cytomegalovirus (hcmv) is a widespread pathogen, the most common congenital viral infection, and the leading cause of infant hepatitis syndrome. in this study, serum samples were collected from 20 hcmv-infected infants with hepatitis and 25 controls. of the 25 infants in the control group, 5 were infected with hcmv but without hepatitis, 10 had hepatitis but no hcmv infection, and 10 were healthy. proteomic expression in the serum was detected by wcx2 chips and surface-enhanced laser desor ...200717705191
acceleration of allograft failure by cytomegalovirus.a number of human herpesviruses are important opportunistic pathogens that have been associated with increased morbidity and mortality in transplant recipients including human cytomegalovirus (hcmv), hhv6, hhv7, hhv8 as well as hsv-1, vzv. however, hcmv has been linked both epidemiologically and through the use of animal models to the acceleration of acute and chronic allograft rejection. this review will cover the pathophysiology, epidemiology, and mechanisms of cmv-associated disease in the se ...200717716883
human cytomegalovirus is present in odontogenic cysts.recent studies suggest that some viruses, including human cytomegalovirus (cmv), may be involved in the pathogenesis of periapical lesions. since periapical cysts (pcs) represent the next stage in the evolution of periapical granuloma, it seemed reasonable to investigate the presence of cmv in pcs and any possible relationship between its presence and the clinical features of those cysts, as well as to compare the results obtained with corresponding findings in non-inflammatory lesions, like odo ...200717803633
the varicella-zoster virus dna encapsidation genes: identification and characterization of the putative terminase subunits.the putative dna encapsidation genes encoded by open reading frames (orfs) 25, 26, 30, 34, 43, 45/42 and 54 were cloned from varicella-zoster virus (vzv) strain ellen. sequencing revealed that the ellen orfs were highly conserved at the amino acid level when compared to those of 19 previously published vzv isolates. additionally, rt-pcr provided the first evidence that orf45/42 was expressed as a spliced transcript in vzv-infected cells. all seven orfs were expressed in vitro and full length pro ...200717868947
differential effects of prednisolone and azathioprine on the development of human cytomegalovirus replication post liver transplantation.we sought to investigate the impact of different immunosuppressive regimens on human cytomegalovirus (hcmv) incidence and replication dynamics in a cohort of 256 patients after liver transplantation.200717876273
cytotrophoblasts infected with a pathogenic human cytomegalovirus strain dysregulate cell-matrix and cell-cell adhesion molecules: a quantitative analysis.studies of intrauterine human cytomegalovirus (cmv) infection have shown suppressed replication in the decidua and placenta of strongly seropositive women. biopsy specimens often contain cmv virion glycoprotein b and dna in syncytiotrophoblasts and villus core macrophages without productive infection. focal replication occurs in placentas of women with low to moderate neutralizing antibody titres. infected cytotrophoblasts downregulate key adhesion and immune molecules required for invasiveness ...200716822542
the switch from latent to productive infection in epstein-barr virus-infected b cells is associated with sensitization to nk cell killing.following activation of epstein-barr virus (ebv)-infected b cells from latent to productive (lytic) infection, there is a concomitant reduction in the level of cell surface major histocompatibility complex (mhc) class i molecules and an impaired antigen-presenting function that may facilitate evasion from ebv-specific cd8+ cytotoxic t cells. in some other herpesviruses studied, most notably human cytomegalovirus (hcmv), evasion of virus-specific cd8+ effector responses via downregulation of surf ...200717079298
the amino-conserved domain of human cytomegalovirus ul80a proteins is required for key interactions during early stages of capsid formation and virus production.assembly of many spherical virus capsids is guided by an internal scaffolding protein or group of proteins that are often cleaved and eliminated in connection with maturation and incorporation of the genome. in cytomegalovirus there are at least two proteins that contribute to this scaffolding function; one is the maturational protease precursor (pul80a), and the other is the assembly protein precursor (pul80.5) encoded by a shorter genetic element within ul80a. yeast gal4 two-hybrid assays esta ...200717079329
exploring the bidirectional interactions between human cytomegalovirus and hepatitis c virus replication after liver transplantation.recurrence of hepatitis c (hcv) post-liver transplantation (lt) is universal and its course is more aggressive than in immunocompetent individuals. human cytomegalovirus (cmv) infection is a common post-lt infection and has immunomodulatory effects that could adversely affect the outcome of hcv. to date, the effect of hcv replication on the dynamics of cmv have not been investigated. from 2000 to 2004, a cohort of 69 hcv-infected liver transplant recipients and 188 hcv-negative liver transplant ...200717192909
antiviral activity of berberine and related compounds against human cytomegalovirus.berberine chloride (1) and the structurally related compounds were assessed for the anti-human cytomegalovirus (hcmv) activity using the plaque assay. the anti-hcmv activity (ic(50) 0.68 microm) of 1 was equivalent to that (ic(50) 0.91 microm) of ganciclovir (gcv). the mechanism of action by which 1 inhibits the replication of hcmv is presumed to be different from that of gcv; 1 would interfere with intracellular events after virus penetration into the host cells and before viral dna synthesis.200717239594
human cytomegalovirus enhances a. actinomycetemcomitans adherence to cells.adherence of actinobacillus actinomycetemcomitans to epithelial cells is an important step in periodontal disease pathogenesis. recent publications describe the subgingival presence of a wide array of viruses [e.g., human cytomegalo-virus (hcmv)]. since viruses can increase cellular susceptibility for bacterial adherence, we investigated whether hcmv renders epithelial cells more prone to adherence by actinobacillus actinomycetemcomitans. cultivated hela and primary epithelial cells were shown t ...200717251519
multimerization of human cytomegalovirus regulatory protein ul69 via a domain that is conserved within its herpesvirus homologues.the ul69 protein of human cytomegalovirus is a multifunctional regulatory protein that has counterparts in all herpesviruses. some of these proteins have been shown to function primarily at the post-transcriptional level in promoting nuclear export of viral transcripts. consistently, this group has reported recently that pul69 is an rna-binding, nucleocytoplasmic shuttling protein that facilitates the cytoplasmic accumulation of unspliced mrna via its interaction with the cellular mrna export fa ...200717251556
dna vaccines expressing glycoprotein complex ii antigens gm and gn elicited neutralizing antibodies against multiple human cytomegalovirus (hcmv) isolates.human cytomegalovirus (hcmv) glycoprotein complex ii (gcii) consists of two glycoproteins, gm and gn. although gcii specific igg purified from hcmv positive patient sera can neutralize hcmv, there has been no report describing the generation of virus-neutralizing antibodies by immunization with individual recombinant gm or gn antigens. in the current study, gm and gn antigens were expressed by the mammalian expression vector pjw4303 and used as dna vaccines to determine the immunogenicity of the ...200717287056
extensive sequence variation exists among isolates of murine cytomegalovirus within members of the m02 family of genes.murine cytomegalovirus (mcmv) is a widely used model for human cytomegalovirus (hcmv) and has facilitated many important discoveries about the biology of cmvs. most of these studies are conducted using the laboratory mcmv strains smith and k181. however, wild-derived isolates of mcmv, like hcmv clinical isolates, exhibit genetic variation from laboratory strains, particularly at the ends of their genomes in areas containing known or putative immune-evasion and tropism genes. this study analysed ...200717325348
development of human cytomegalovirus-specific t cell immunity during primary infection of pregnant women and its correlation with virus transmission to the fetus.we sought to study the development of human cytomegalovirus (hcmv)-specific t cell-mediated immune responses during primary hcmv infection in pregnancy.200717330798
human cytomegalovirus glycoprotein b genotype correlates with different symptoms of infected infants.human cytomegalovirus (hcmv) is the pathogen of cytomegalic inclusion disease of infants. hcmv strains can be classified into four genotypes of glycoprotein b (gb). there are limited data concerning links between clinical symptoms and hcmv genotypes. the aims of the present study were to determine the genotype of hcmv isolates from pediatric patients who have different symptoms on the assumption that the gb genotype may influence the outcomes of congenital and prenatal hcmv infection.200717356299
the immunological burden of human cytomegalovirus infection.cytomegalovirus (cmv) is a persistent dna virus that has evolved with humans to establish a finely balanced host-virus relationship. this balance is maintained by host immune surveillance since deficiencies in these processes can result in life-threatening disease, as observed in immunologically immature neonates and pharmacologically immunosuppressed transplant recipients. both t cells and natural killer cells are intimately involved in maintaining asymptomatic infection by specific and non-spe ...200718219760
murine gammaherpesvirus 68 serum antibodies in general human population.previous studies using elisa and virus neutralization test (vnt) have proved the presence of murine gammaherpesvirus 68 (mhv-68) serum antibodies in sera of laboratory staff working with mhv-68, as well as in the general population. in this study, we investigated the incidence of serum antibodies to mhv-68 and to human herpesviruses presumably antigenically similar to mhv-68, as herpes simplex virus 1 (hsv-1), human cytomegalovirus (hcmv), and epstein-barr virus (ebv), in general population usin ...200718197737
comments on "cytomegalovirus (cmv)-encoded ul144 (truncated tumor necrosis factor receptor) and outcome of congenital cmv infection". 200718008260
[polymorphism of human cytomegalovirus ul134 gene in low-passage clinical isolates].human cytomegalovirus (hcmv) displays genetic polymorphisms. nineteen open reading frames (orfs, ul133-ul151) found in the toledo strain of hcmv and other low-passage clinical isolates may be essential for viral infection. this study aimed to analyze the polymorphism of hcmv ul134 gene in clinical isolates and explore the relationship between the polymorphism and hcmv infection.200718082047
infection of human endothelium in vitro by cytomegalovirus causes enhanced expression of purinergic receptors: a potential virus escape mechanism?human cytomegalovirus (cmv) uses different strategies to escape from human host defense reactions. previously we have observed that infection of endothelial cells with cmv in vitro leads to enhanced activity of endothelial ectonucleotidases. these ectoenzymes are responsible for hydrolysis of extracellular adenine nucleotides, resulting in the formation of adenosine. infection with cmv in vivo therefore may result in local increase of adenosine production, providing an anti-inflammatory and anti ...200718049120
subgingival human cytomegalovirus correlates with increased clinical periodontal parameters and bacterial coinfection in periodontitis.viruses from the herpesviridae family may be implicated in the pathogenesis of periodontal disease. the aim of this investigation was to compare the subgingival frequency of human cytomegalovirus (hcmv) in subjects affected by periodontitis to periodontally healthy subjects and to assess the correlation of hcmv with periodontal clinical parameters and periodontopathic bacteria.200718052702
differential inhibition of human cytomegalovirus (hcmv) by toll-like receptor ligands mediated by interferon-beta in human foreskin fibroblasts and cervical tissue.human cytomegalovirus (hcmv) can be acquired sexually and is shed from the genital tract. cross-sectional studies in women show that changes in genital tract microbial flora affect hcmv infection and/or shedding. since genital microbial flora may affect hcmv infection or replication by stimulating cells through toll-like receptors (tlr), we assessed the effects of defined tlr-ligands on hcmv replication in foreskin fibroblasts and ectocervical tissue. poly i:c (a tlr3-ligand) and lipopolysacchar ...200718053251
monitoring of human cytomegalovirus infection in immunosuppressed patients using real-time pcr on whole blood.quantitative monitoring of human cytomegalovirus (hcmv) is currently used in the follow-up of immunosuppressed patients.200717904901
synthesis and antiviral evaluation of alkoxyalkyl-phosphate conjugates of cidofovir and adefovir.esterification of cidofovir (cdv), an antiviral nucleoside phosphonate, with alkyl or alkoxyalkyl groups increases antiviral activity by enhancing cell uptake and conversion to cdv diphosphate. hexadecyloxypropyl-cdv (hdp-cdv) has been shown to be 40-100 times more active than cdv in vitro in cells infected with herpes group viruses, variola, cowpox, vaccinia or ectromelia viruses. since the first phosphorylation of cdv may be rate limiting, we synthesized the hexadecyloxypropyl-phosphate (hdp-p ...200717367874
the human cytomegalovirus mhc class i homolog ul18 inhibits lir-1+ but activates lir-1- nk cells.the inhibitory leukocyte ig-like receptor 1 (lir-1, also known as ilt2, cd85j, or lilrb1) was identified by its high affinity for the human cmv (hcmv) mhc class i homolog gpul18. the role of this lir-1-gpul18 interaction in modulating nk recognition during hcmv infection has previously not been clearly defined. in this study, lir-1(+) nkl cell-mediated cytotoxicity was shown to be inhibited by transduction of targets with a replication-deficient adenovirus vector encoding ul18 (rad-ul18). fibrob ...200717372005
cytoplasmic envelopment of human cytomegalovirus requires the postlocalization function of tegument protein pp28 within the assembly compartment.the assembly of herpesvirus remains incompletely defined due to the structural complexity of these viruses. although the assembly of the capsid of these large dna viruses is well studied and reasonably well conserved for all members of this diverse family of viruses, the cytoplasmic processes of tegumentation and envelopment are not well understood. the virion of the largest human herpesvirus, human cytomegalovirus (hcmv), contains over 70 virus-encoded proteins that are incorporated during a nu ...200717392372
increased expression of p53 enhances transcription-coupled repair and global genomic repair of a uvc-damaged reporter gene in human cells.ultraviolet (uv) light-induced dna damage is repaired by nucleotide excision repair, which is divided into two sub-pathways: global genome repair (ggr) and transcription-coupled repair (tcr). while it is well established that the ggr pathway is dependent on the p53 tumour suppressor protein in human cells, both p53-dependent and p53-independent pathways have been reported for tcr. in the present work, we investigated the role of p53 in both ggr and tcr of a uvc-damaged reporter gene in human fib ...200717196445
high-frequency epigenetic repression and silencing of retroviruses can be antagonized by histone deacetylase inhibitors and transcriptional activators, but uniform reactivation in cell clones is restricted by additional mechanisms.integrated retroviral dna is subject to epigenetic gene silencing, but the viral and host cell properties that influence initiation, maintenance, and reactivation are not fully understood. here we describe rapid and high-frequency epigenetic repression and silencing of integrated avian sarcoma virus (asv)-based vector dnas in human hela cells. initial studies utilized a vector carrying the strong human cytomegalovirus (hcmv) immediate-early (ie) promoter to drive expression of a green fluorescen ...200717202206
effect of serum and ctl on focal growth of human cytomegalovirus.in immunocompromised patients only cytotoxic t-lymphocytes (ctl) but not antiviral antibodies appear to be efficient in control of human cytomegalovirus (hcmv) infection. this is contrasted by the well-documented neutralising activity of patient sera against standard hcmv strains.200717204454
the carboxy-terminal domain of glycoprotein n of human cytomegalovirus is required for virion morphogenesis.glycoproteins m and n (gm and gn, respectively) are among the few proteins that are conserved across the herpesvirus family. the function of the complex is largely unknown. whereas deletion from most alphaherpesviruses has marginal effects on the replication of the respective viruses, both proteins are essential for replication of human cytomegalovirus (hcmv). we have constructed a series of mutants in gn to study the function of this protein. gn of hcmv is a type i glycoprotein containing a sho ...200717229708
knockdown of hdaxx in normally non-permissive undifferentiated cells does not permit human cytomegalovirus immediate-early gene expression.the cellular protein human daxx (hdaxx), a component of nuclear domain 10 structures, is known to mediate transcriptional repression of human cytomegalovirus immediate-early (ie) gene expression upon infection of permissive cell types, at least in part, by regulation of chromatin structure around the major ie promoter (miep). as it is now clear that differentiation-dependent regulation of the miep also plays a pivotal role in the control of latency and reactivation, we asked whether hdaxx-mediat ...200717947514
human cytomegalovirus ul145 gene is highly conserved among clinical strains.human cytomegalovirus (hcmv), a ubiquitous human pathogen, is the leading cause of birth defects in newborns. a region (referred to as ul/b') present in the toledo strain of hcmv and low-passage clinical isolates) contains 22 additional genes,which are absent in the highly passaged laboratory strain ad169. one of these genes,ul145 open reading frame (orf), is located between the highly variable genes ul144 and ul146. to assess the structure of the ul145 gene,the ul145 orf was amplified by pcr an ...200717954963
[capture and detection of human cytomegalovirus (hcmv) igm by a recombinant multi-epitope chimeric antigen].to establish a sensitive and specific antibody-capture enzyme-linked immunosorbent assay (ac-elisa) method to detect serum igm against human cytomegalovirus (hcmv) by expressing a recombinant hcmv multi-epitope cheimeric antigen through genetic engineering. the dominant epitopes of hcmv were analyzed and selected by computer software a recombinant multi-epitope chimeric antigen expression vector including hcmv dna was constructed, and transformed into e. coli bl21(de3). the antigen was abundantl ...200717989044
molecular basis of persistence and latencyhuman cytomegalovirus (hcmv) is an ubiquitous β-herpesvirus that establishes a lifelong infection within the host. although hcmv is generally asymptomatic within the normal individual, the virus causes severe and incapacitating disease in immune compromised patients (pass, 2001). a critical component for hcmv persistence in the non-immune compromised host is the ability of the virus to establish cellular sites of latency as well as persistent infection. during latency, ...200721348100
specific short hairpin rna-mediated inhibition of viral dna packaging of human cytomegalovirus.to clearly demonstrate the role of the human cytomegalovirus (hcmv) portal protein pul104 rna interference was applied. expressing cell lines were constructed by transduction of shrnas via the infection with retroviral vectors. after infection of these cells with hcmv ad169 the expression of pul104 was reduced up to 80% for shrna s1 and 54% for shrna s2 at late times of infection compared to controls. in addition, the inhibitory effect was corresponding with a decrease in viral mrna and plaque f ...200617056039
monitoring human cytomegalovirus (hcmv) in hcmv-seropositive orthotopic liver-transplant recipients by means of quantitative real-time polymerase chain reaction.human cytomegalovirus can be reactivated after orthotopic liver transplantation in patients who are seropositive for cytomegalovirus. whether those cytomegalovirus-seropositive patients require immediate posttransplant (anti)- cytomegalovirus prophylactic therapy or preemptive treatment as opposed to deferred treatment remains controversial. the aims of our study were to evaluate the relevance of cytomegalovirus monitoring with quantitative real-time polymerase chain reaction in whole blood and ...200617238855
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