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infection of porcine cells with human herpesviruses.porcine organs are valuable candidate materials for xenotransplantation to humans. long-term maintenance of well functioning transplants is a prerequisite for success. transplanted organs may be damaged by immune reactions or by infectious agents in hosts. human herpesviruses (hhvs) establish life-long latency in humans after a primary infection. they can be reactivated with various stimuli, including immunosuppression. this study was performed to verify the infectivity of some hhvs toward porci ...201020692426
the human cytomegalovirus microrna mir-ul112 acts synergistically with a cellular microrna to escape immune elimination.although approximately 200 viral micrornas are known, only very few share similar targets with their host's micrornas. a notable example of this is the stress-induced ligand micb, which is targeted by several distinct viral and cellular micrornas. through the investigation of the microrna-mediated immune-evasion strategies of herpesviruses, we initially identified two new cellular micrornas that targeted micb and were expressed differently both in healthy tissues and during melanocyte transforma ...201020694010
the p97 atpase dislocates mhc class i heavy chain in us2-expressing cells via a ufd1-npl4-independent mechanism.the human cytomegalovirus (hcmv) protein us2 hijacks the endoplasmic reticulum (er)-associated degradation machinery to dispose of mhc class i heavy chain (hc) at the er. this process requires retrotranslocation of newly synthesized hc molecules from the er membrane into the cytosol, but the mechanism underlying the dislocation reaction has been elusive. here we establish an in vitro permeabilized cell assay that recapitulates the retrotranslocation of mhc hc in us2-expressing cells. using this ...201020702414
identification of novel allosteric nonpeptidergic inhibitors of the human cytomegalovirus-encoded chemokine receptor us28.human cytomegalovirus (hcmv) is a widespread human pathogen, possessing onco-modulatory properties. constitutive signaling of the hcmv-encoded chemokine receptor us28 and its ability to bind a broad spectrum of chemokines might facilitate hcmv-associated tumor progression. novel nonpeptidergic chemotypes were identified as neutral antagonists or inverse agonists on us28, that allosterically inhibit chemokine binding to us28.201020031418
prevalence and activity of epstein-barr virus and human cytomegalovirus in symptomatic and asymptomatic apical periodontitis lesions.apical periodontitis is a polymicrobial inflammation with a dominant flora of opportunistic gram-negative bacteria; however, a pathogenic role of human herpesviruses such as epstein-barr virus (ebv) and human cytomegalovirus (hcmv) has been implicated recently. the aims of this study were to determine the prevalence, activity, and disease association of ebv and hcmv in apical periodontitis in an eastern hungarian population.201020728714
the carboxy-terminal segment of the human cytomegalovirus dna polymerase accessory subunit ul44 is crucial for viral replication.the amino-terminal 290 residues of ul44, the presumed processivity factor of human cytomegalovirus dna polymerase, possess all of the established biochemical activities of the full-length protein, while the carboxy-terminal 143 residues contain a nuclear localization signal (nls). we found that although the amino-terminal domain was sufficient for origin-dependent synthesis in a transient-transfection assay, the carboxy-terminal segment was crucial for virus replication and for the formation of ...201020739543
the effects of maribavir on the autophosphorylation of ganciclovir resistant mutants of the cytomegalovirus ul97 protein.abstract:201021429239
host-viral effects of chromatin assembly factor 1 interaction with hcmv ie2.chromatin assembly factor 1 (caf1) consisting of p150, p60 and p48 is known to assemble histones onto newly synthesized dna and thus maintain the chromatin structure. here, we show that caf1 expression was induced in human cytomegalovirus (hcmv)-infected cells, concomitantly with global chromatin decondensation. this apparent conflict was thought to result, in part, from caf1 mislocalization to compartments of hcmv dna synthesis through binding of its largest subunit p150 to viral immediate-earl ...201121445097
inhibition of 2',5'-oligoadenylate synthetase expression and function by the human cytomegalovirus orf94 gene product.the human cytomegalovirus (hcmv) orf94 gene product has been reported to be expressed during both productive and latent phases of infection, although its function is unknown. we report that expression of porf94 leads to decreased 2',5'-oligoadenylate synthetase (oas) expression in transfected cells with and without interferon stimulation. furthermore, the functional activity of oas was inhibited by porf94. finally, we present evidence of oas modulation by porf94 during productive hcmv infection ...201121450824
histone deacetylase 3, not histone deacetylase 2, interacts with the major immediate early locus of human cytomegalovirus.evidence suggests that genome chromatinization and the posttranslational modification of histones are involved in the regulation of viral gene expression, including the human cytomegalovirus (hcmv). we performed a chip-on-chip assay to determine whether histone deacetylases (hdacs) interact with hcmv genomic dna on a global level. surprisingly, we found that hdac3, but not hdac2, interacts not only with the major immediate early (mie) promoter but also with the entire mie locus, suggesting a het ...201121453528
human cytomegalovirus induces the activity and expression of acetyl-coenzyme a carboxylase, a fatty acid biosynthetic enzyme whose inhibition attenuates viral replication.we have previously reported that human cytomegalovirus (hcmv) infection induces large-scale changes to host cell glycolytic, nucleic acid, and phospholipid metabolism. here we explore the viral mechanisms involved in fatty acid biosynthetic activation. our results indicate that hcmv targets acc1, the rate-limiting enzyme of fatty acid biosynthesis, through multiple mechanisms. hcmv infection was found to activate acc1 expression, increasing the abundance of both acc1 mrna and protein. viral gene ...201121471234
yeast two hybrid analyses reveal novel binary interactions between human cytomegalovirus-encoded virion proteins.human cytomegalovirus (hcmv) is the largest human herpesvirus and its virion contains many viral encoded proteins found in the capsid, tegument, and envelope. in this study, we carried out a yeast two-hybrid (yth) analysis to study potential binary interactions among 56 hcmv-encoded virion proteins. we have tested more than 3,500 pairwise combinations for binary interactions in the yth analysis, and identified 79 potential interactions that involve 37 proteins. forty five of the 79 interactions ...201121483780
nuclear body formation and pml body remodeling by the human cytomegalovirus protein ul35.the human cytomegalovirus (hcmv) ul35 gene encodes two proteins, ul35 and ul35a. expression of ul35 in transfected cells results in the formation of ul35 nuclear bodies that associate with promyelocytic leukemia (pml) protein. pml forms the basis for pml nuclear bodies that are important for suppressing viral lytic gene expression. given the important relationship between pml and viral infection, we have further investigated the association of ul35 with pml bodies. we demonstrate that ul35 bodie ...201121489587
stimulation of homology-directed repair at i-scei-induced dna breaks during the permissive life cycle of human cytomegalovirus.human cytomegalovirus (hcmv) selectively relocalizes many dna repair proteins, thereby avoiding a potentially detrimental damage response. in the present study, we evaluated interactions between hcmv and the homology-directed repair (hdr) pathway. in permissive human foreskin fibroblasts, a fluorescence-based double-stranded break repair assay was used to determine that hcmv stimulated hdr. repair of both stably integrated and extrachromosomal reporter substrates was observed to increase. hdr wa ...201121490102
the human cytomegalovirus gene products essential for late viral gene expression assemble into pre- replication complexes before viral dna replication.the regulation of human cytomegalovirus (hcmv) late gene expression by viral proteins is poorly understood and these viral proteins could be a target for novel antivirals. hcmv open reading frames (orfs) ul79, 87, and 95 have homology with late gene transcription factors of murine gammaherpesvirus 68 orfs 18, 24, and 34, respectively. to determine whether these hcmv proteins are also essential for late gene transcription of a betaherpesvirus, we mutated hcmv orfs ul79, 87, or 95. cells were infe ...201121507978
evidence for positive selection in the extracellular domain of human cytomegalovirus encoded g protein-coupled receptor us28.the human cytomegalovirus (hcmv)-encoded chemokine receptor us28 is also a seven-transmembrane g-protein coupled receptor, whose signaling pathway is known for its involvement in host immune system evasion. hcmv infection can result in serious disease in immunocompromised individuals and is also linked to atherosclerosis and cardiovascular disease. identifying amino acid residues that play a crucial role in successful viral adaptation in response to the host's immune defense is critical for effe ...201121520142
regulation of nucleocytoplasmic trafficking of viral proteins: an integral role in pathogenesis?signal-dependent targeting of proteins into and out of the nucleus is mediated by members of the importin (imp) family of transport receptors, which recognise targeting signals within a cargo protein and mediate passage through the nuclear envelope-embedded nuclear pore complexes. regulation of this process is paramount to processes such as cell division and differentiation, but is also critically important for viral replication and pathogenesis; phosphorylation appears to play a major role in r ...201121530593
association of human herpesvirus 6 subtypes with symptomatic apical periodontitis.objective: the occurrence of human herpesvirus (hhv) 6 subtypes a and b in apical periodontitis was determined. the relationship of hhv-6 subtypes to other disease associated herpesviruses, i.e., epstein-barr virus (ebv) and human cytomegalovirus, was also investigated. study design: forty apical periodontitis samples (17 symptomatic and 23 asymptomatic) and 40 healthy pulp control samples were collected. nested polymerase chain reaction was used to detect hhv-6 dna. results: hhv-6 dna was obser ...201121546281
comparison of real-time pcr to elisa for the detection of human cytomegalovirus infection in renal transplant patients in the sudan.abstract: background: this study was carried out to detect human cytomegalovirus (hcmv) igg and igm antibodies using an enzyme-linked immunosorbent assay (elisa) in renal transplant patients in khartoum state, sudan and to improve the diagnosis of hcmv through the introduction of real-time polymerase chain reaction (pcr) testing. a total of 98 plasma samples were collected randomly from renal transplant patients at ibin sina hospital and salma centre for transplantation and haemodialysis during ...201121569506
genetic and viral etiology of glioblastoma--a unifying hypothesis.growing body of evidence implicates human cytomegalovirus (hcmv) in the etiology of glioblastoma (gbm). although hcmv is a ubiquitous herpesvirus, only a minority of those infected develop gbm, suggesting the involvement of host genetic factors in susceptibility to hcmv-induced/spurred gbm. hcmv has evolved a large repertoire of strategies for decreasing the efficacy of the host immune response and interfering with viral clearance. one strategy involves the generation of proteins that have funct ...201121586624
an e2f1-mediated dna damage response contributes to the replication of human cytomegalovirus.dna damage resulting from intrinsic or extrinsic sources activates dna damage responses (ddrs) centered on protein kinase signaling cascades. the usual consequences of inducing ddrs include the activation of cell cycle checkpoints together with repair of the damaged dna or induction of apoptosis. many dna viruses elicit host ddrs during infection and some viruses require the ddr for efficient replication. however, the mechanism by which ddrs are activated by viral infection is poorly understood. ...201121589897
human cytomegalovirus infection is detected frequently in stillbirths and is associated with fetal thrombotic vasculopathy.(see the editorial commentary by pereira, on pages 1510-2.) background. human cytomegalovirus (cmv) is the most common congenital infection in developed countries and is a known cause of intrauterine fetal death. we examined cmv infection in stillbirths and the relationship with histopathological findings at autopsy. methods. we collected liver, kidney, and placenta specimens from 130 stillbirths. cmv dna and protein were detected using polymerase chain reaction and immunohistochemistry, along w ...201121592980
comparison of the performance of polymerase chain reaction and pp65 antigenemia for the detection of human cytomegalovirus in immunosuppressed patients.introduction: human cytomegalovirus (hcmv) is often reactive in latently infected immunosuppressed patients. accordingly, hcmv remains one of the most common infections following solid organ and hemopoietic stem cell transplantations, resulting in significant morbidity, graft loss and occasional mortality. the early diagnosis of hcmv disease is important in immunosuppressed patients, since in these individuals, preemptive treatment is useful. the objective of this study was to compare the perfor ...201121625804
synthesis, transport and antiviral activity of ala-ser and val-ser prodrugs of cidofovir.we report the synthesis and biological evaluation of ala-(val-)l-ser-co(2)r prodrugs of 1, where a dipeptide promoiety is conjugated to the p(oh)(2) group of cidofovir (1) via esterification by the ser side chain hydroxyl group and an ethyl group (4 and 5) or alone (6 and 7). in a murine model, oral administration of 4 or 5 did not significantly increase total cidofovir species in the plasma compared to 1 or 2, but 7 resulted in a 15-fold increase in a rat model and had an in vitro ec(50) value ...201121641218
human cytomegalovirus ul7, a homologue of the slam-family receptor cd229, impairs cytokine production.human cytomegalovirus (hcmv), the ╬▓-herpesvirus prototype, has evolved a wide spectrum of mechanisms to counteract host immunity. among them, hcmv uses cellular captured genes encoding molecules capable of interfering with the original host function or of fulfilling new immunomodulatory tasks. here, we report on ul7, a novel hcmv heavily glycosylated transmembrane protein, containing an ig-like domain that exhibits remarkable amino acid similarity to cd229, a cell-surface molecule of the signal ...201121670740
tyrosine-based 1-(s)-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine and -adenine ((s)-hpmpc and (s)-hpmpa) prodrugs: synthesis, stability, antiviral activity, and in vivo transport studies.eight novel single amino acid (6-11) and dipeptide (12, 13) tyrosine p-o esters of cyclic cidofovir ((s)-chpmpc , 4) and its cyclic adenine analogue ((s)-chpmpa, 3) were synthesized and evaluated as prodrugs. in vitro ic(50) values for the prodrugs (<0.1-50 μm) vs vaccinia, cowpox, human cytomegalovirus, and herpes simplex type 1 virus were compared to those for the parent drugs ((s)-hpmpc, 2; (s)-hpmpa, 1; ic(50) 0.3-35 μm); there was no cytoxicity with kb or hff cells at ≤100 μm. the prodrugs ...201121812420
characterization of human cytomegalovirus ul145 and ul136 genes in low-passage clinical isolates from infected chinese infants.background: human cytomegalovirus (hcmv) is a leading cause of morbidity and mortality in immunocompromised individuals. the unique long b' (ulb') region of hcmv contains at least 19 open reading frames (orfs); however, little is known about the function of ul145 and ul136. we characterized ul145 and ul136 in low-passage clinical isolates from chinese infants.<br /> material/methods: the clinical strains of hcmv were recovered from the urine from hcmv-infected infants. human embryonic lung fibro ...201121804461
cyclopropavir inhibits the normal function of the human cytomegalovirus ul97 kinase.cyclopropavir (cpv) is active against human cytomegalovirus (cmv) as well as both variants of human herpes virus 6 and human herpesvirus 8. the mechanism of action of cpv against cmv is similar to that of ganciclovir (gcv) in that it is phosphorylated initially by the cmv ul97 kinase resulting in inhibition of viral dna synthesis. resistance to cpv maps to the ul97 kinase, but is associated primarily with h520q mutations and thus retains good antiviral activity against most gcv-resistant isolate ...201121788463
identification of novel allosteric modulators for the g-protein coupled us28 receptor of human cytomegalovirus.the highly constitutively active g-protein coupled receptor us28 of human cytomegalovirus (hcmv) is an interesting pharmacological target because of its implication on viral dissemination, cardiovascular diseases and tumorigenesis. we found that dihydroisoquinolinone and tetrahydroisoquinoline scaffolds may be promising lead structures for novel us28 allosteric inverse agonists. these scaffolds were rapidly synthesized by radical carboamination reactions followed by non-radical transformations. ...201121784633
the enhanced host-cell permissiveness of human cytomegalovirus is mediated by the ras signaling pathway.hcmv utilizes cellular signal transduction pathways to activate viral or cellular transcription factors involved in the control of viral gene expression and dna replication. in the present study, we demonstrate that h-ras-transformed cells show increased permissiveness to hcmv when compared to their parental non-transformed cells. both the progeny viral yield and the protein levels were elevated in the hcmv-infected h-ras-transformed cells requiring active viral gene replication, as shown by the ...201121782855
divergent effects of human cytomegalovirus and herpes simplex virus-1 on cellular metabolism.viruses rely on the metabolic network of the host cell to provide energy and macromolecular precursors to fuel viral replication. here we used mass spectrometry to examine the impact of two related herpesviruses, human cytomegalovirus (hcmv) and herpes simplex virus type-1 (hsv-1), on the metabolism of fibroblast and epithelial host cells. each virus triggered strong metabolic changes that were conserved across different host cell types. the metabolic effects of the two viruses were, however, la ...201121779165
inhibitory effects of tricin derivative from sasa albo-marginata on replication of human cytomegalovirus.the anti-human cytomegalovirus (hcmv) activity of tricin (4',5,7-trihydroxy-3',5'-dimethoxyflavone), a derivative from sasa albo-marginata, was studied in the human embryonic fibroblast cell line mrc-5. in a plaque assay, tricin and ganciclovir (gcv) showed concentration-dependent inhibitory properties from 0.05 to 3.6µm and 0.01 to 1.0µm, respectively. tricin had no virucidal effects on cell-free hcmv. treatment with tricin 1h before, or 1h or 3h after viral infection significantly suppressed h ...201121745500
vesicular stomatitis virus has extensive oncolytic activity against human sarcomas: rare resistance is overcome by blocking interferon pathways.oncolytic viruses have been tested against many carcinomas of ectodermal and endodermal origin; however, sarcomas, arising from mesoderm, have received relatively little attention. using 13 human sarcomas representing seven tumor types, we assessed the efficiency of infection, cytolysis, and replication of green fluorescent protein (gfp)-expressing vesicular stomatitis virus (vsv) and its oncolytically enhanced mutant vsv-rp30a. both viruses efficiently infected and killed 12 of 13 sarcomas. vsv ...201121734048
heteromerization of human cytomegalovirus encoded chemokine receptors.human cytomegalovirus (hcmv) is a widespread pathogen that infects up to 80% of the human population and causes severe complications in immunocompromised patients. hcmv expresses four seven transmembrane (7tm) spanning/g protein-coupled receptors (gpcrs) - us28, us27, ul33 and ul78 - that show close homology to human chemokine receptors. while us28 was shown to bind several chemokines and to constitutively activate multiple signaling cascades, the function(s) of us27, ul33 and ul78 in the viral ...201121684267
detection of human cytomegalovirus in motile spermatozoa and spermatogenic cells in testis organotypic culture.abstract:201121711549
assessment of human cytomegalovirus co-infection in egyptian chronic hcv patients.abstract: human cytomegalovirus (hcmv) is the most common cause of severe morbidity and mortality in immune- compromised individuals. this study was conducted to determine the incidence of hcmv infection in hcv patients who either spontaneously cleared the virus or progressed to chronic hcv infection. the study included a total of eighty four cases (48 females and 36 males) that were referred to blood banks for blood donation with an age range of 18-64 years (mean age 37.62 -¦ 10.03 years). hepa ...201121740595
serum antibody response to the gh/gl/pul128-131 five-protein complex of human cytomegalovirus (hcmv) in primary and reactivated hcmv infections.background: recently, a new human cytomegalovirus (hcmv) glycoprotein complex has been identified and potentially proposed as a vaccine. objective: the aim of this study was to determine whether the hcmv gh/gl/pul128-pul130-pul131 (gh/gl/pul128-131) 5-protein (pentameric) complex (which has been recently found to be indispensable for the infection of endothelial and epithelial cells) is able to elicit a consistent antibody response in both primary and reactivated hcmv infections. study design: t ...201121820353
general blockade of hcmv immediate early mrna expression in s/g2 by a nuclear, daxx- and pml-independent mechanism.the onset of human cytomegalovirus (hcmv) lytic replication is strictly controlled by the host cell division cycle. although viral entry of s/g2 phase cells is unperturbed expression of major immediate early (mie) genes ie1 and ie2 is tightly blocked in these cells. besides the finding that cyclin-dependent kinase (cdk) activity is required for ie1/ie2 repression little is known about the nature of this cell cycle-dependent block. here, we show that the block occurs after nuclear entry of viral ...201121832009
herpesvirus carriage in saliva and posttreatment apical periodontitis: searching for association.objective: herpesvirus infection can cause immunosuppression and then act as a modifier of apical periodontitis, influencing the disease severity and response to treatment. the purpose of this study was to investigate if herpesvirus infection, as inferred by salivary carriage, may influence the endodontic treatment outcome. study design: the study population included 72 patients who had root canals treated more than 1 year previously because of necrotic pulps and apical periodontitis. at the fol ...201121831677
pparγ and human trophoblast differentiation.the peroxisome proliferator-activated receptor-γ (pparγ) is a member of the nuclear receptor superfamily that controls in a ligand-dependent manner the expression of a large array of genes involved in the control of energy homeostasis and in cell differentiation, proliferation, apoptosis, and the inflammatory process. unexpectedly, genetic studies performed in mice established that pparγ is essential for placental development. in the human placenta, pparγ is specifically expressed in the trophob ...201121704384
human cytomegalovirus infection maintains mtor activity and its perinuclear localization during amino acid deprivation.the mammalian target of rapamycin (mtor) kinase is present in 2 functionally distinct complexes, mtor complex 1 (mtorc1) and complex 2 (mtorc2). active mtorc1 mediates phosphorylation of eif4e-binding protein (4e-bp) and p70 s6 kinase (s6k), which is important for maintaining translation. during human cytomegalovirus (hcmv) infection, cellular stress responses are activated that normally inhibit mtorc1; however, previous data show that hcmv infection circumvents stress responses and maintains mt ...201121734039
summary of the 9th annual meeting of the italian society for virology.the 9th annual meeting of the italian society for virology (siv) comprised seven plenary sessions focused on: general virology and viral genetics; virus-host interaction and pathogenesis; viral oncology; emerging viruses and zoonotic, foodborne, and environmental pathways of transmission; viral immunology and vaccines; medical virology and antiviral therapy; viral biotechnologies and gene therapy. moreover, four hot topics were discussed in special lectures: the pioneer in human virology lecture ...201120799282
human cytomegalovirus ul97 kinase prevents the deposition of mutant protein aggregates in cellular models of huntington's disease and ataxia.the presence of aggregates of abnormally expanded polyglutamine (polyq)-containing proteins are a pathological hallmark of a number of neurodegenerative diseases including huntington's disease (hd) and spinocerebellar ataxia-3 (sca3). previous studies in cellular, drosophila, and mouse models of hd and sca have shown that neurodegeneration can be prevented by manipulations that inhibit polyq aggregation. we have shown that the ul97 kinase of the human cytomegalovirus (hcmv) prevents aggregation ...201120732421
natural history of cytomegalovirus infection in a series of patients diagnosed with moderate-severe ulcerative colitis.to evaluate the natural history of human cytomegalovirus (hcmv) infection in a series of 28 ulcerative colitis patients in whom the search for hcmv was positive.201121350712
human cytomegalovirus ul97 d605e polymorphism has a high prevalence in immunocompetent japanese infants and children.there is no existing data on ul97 mutation in human cytomegalovirus (hcmv) isolates obtained from individuals who have never been exposed to ganciclovir (gcv). ul97 codons 439 to 645 from 61 cmv isolates from 61 immunocompetent japanese infants and children were sequenced directly. no known gcv resistance mutations were found, meaning that the ul97 mutation had resulted from the use of gcv. on the other hand, a mutation at codon 605 (d to e) was frequently identified (56/61: 91.8%). this could b ...201121362026
[evaluation of riboflavin photochemical inactivation efficacy of virus in red blood cells by using animal models].this study was aimed to evaluate the efficacy of riboflavin photochemical inactivation of virus in red blood cells by using animal models. human cytomegalovirus (hcmv) plus red blood cells were used as indicator, 30 bala/c mice were divided into the experimental group (n = 10), virus control group (n = 10), visible light control group (n = 5) and red blood cell control group (n = 5). mice in experimental group were inoculated with red blood cells inactive by the riboflavin photochemical, mice in ...201121362258
the human cytomegalovirus gene ul79 is required for the accumulation of late viral transcripts.in this study, we adopted a conditional protein genetic approach to characterize the role of the human cytomegalovirus (hcmv) gene ul79 during virus infection. we constructed adddul79, a recombinant hcmv in which the annotated ul79 open reading frame (orf) was tagged with the destabilization domain of a highly unstable variant of the human fkbp12 protein (ddfkbp). the ddfkbp domain targets the tagged protein for rapid proteasomal degradation, but the synthetic ligand shield-1 can stabilize ddfkb ...201121367901
human cytomegalovirus is protected from inactivation by reversible binding to villous trophoblasts.human cytomegalovirus (hcmv) is the leading cause of congenital disease in the developed world. transmission of hcmv to the fetus can occur through the villous placenta. previously, we have shown that although syncytiotrophoblast (st) can be productively infected, it is more likely that hcmv reaches the fetus through breaks in the st than through basal release of progeny virus from infected st. progeny virus released on the maternal side could interact back with the st and accumulate. in pregnan ...201121368297
viral etiology of aseptic meningitis among children in southern iran.aseptic meningitis refers to a clinical syndrome of meningeal inflammation in which bacteria cannot be identified in the cerebrospinal fluid (csf). the viral etiology and the epidemiological, clinical, and laboratory characteristics of aseptic meningitis among children aged 2 months to 15 years in shiraz, southern iran were determined. from may 2007 to april 2008, 65 patients were admitted to the hospital with aseptic meningitis. seven viruses, non-polio human enteroviruses, mumps virus, herpes ...201121412795
human t-lymphotropic virus tax activates human cytomegalovirus major-immediate early promoter and improves production of recombinant proteins in hek293 cells.the human cytomegalovirus (cmv) major immediate-early (mie) promoter is widely used in mammalian cells for production of recombinant proteins. it is of great interest to further enhance protein production driven by the cmv promoter. here, we report that the tax protein of human t-lymphotropic virus stimulates the transgene expression under the control of cmv mie promoter in hek293 cells. at least threefold increases in transient production of recombinant proteins, including luciferase and two bi ...201121425252
The latency-associated UL138 gene product of human cytomegalovirus sensitizes cells to tumor necrosis factor alpha (TNF-alpha) signaling by upregulating TNF-alpha receptor 1 cell surface expression.Many viruses antagonize tumor necrosis factor alpha (TNF-a) signaling in order to counteract its antiviral properties. One way viruses achieve this goal is to reduce TNF-a receptor 1 (TNFR1) on the surface of infected cells. Such a mechanism is also employed by human cytomegalovirus (HCMV), as recently reported by others and us. On the other hand, TNF-a has also been shown to foster reactivation of HCMV from latency. By characterizing a new variant of HCMV AD169, we show here that TNFR1 downregu ...201121880774
the multi-targeted kinase inhibitor sorafenib inhibits human cytomegalovirus replication.human cytomegalovirus (hcmv) is a major pathogen in immunocompromised individuals. here, non-toxic concentrations of the anti-cancer kinase inhibitor sorafenib were shown to inhibit replication of different hcmv strains (including a ganciclovir-resistant strain) in different cell types. in contrast to established anti-hcmv drugs, sorafenib inhibited hcmv major immediate early promoter activity and hcmv immediate early antigen (iea) expression. sorafenib is known to inhibit raf. comparison of sor ...201120803231
[Effects of human cytomegalovirus on the cell cycle of duct epithelial cell cultures of human salivary gland in vitro and relative mechanism].To investigate the effects of human cytomegalovirus (HCMV) on the cell cycle of duct epithelial cell cultures of human salivary gland (HSG) in vitro and relative mechanism.201121977588
anti-hcmv igg positivity rate among renal transplant recipients in baghdad.in developing countries, the majority of infection by human cytomegalovirus (hcmv) occurs during childhood and continues as a latent infection. by adulthood, almost all the population may show anti-hcmv igg as positive. this study was undertaken to determine the correlation between the prevalence of hcmv antibodies and hcmv infection during post transplant period among renal transplant patients in baghdad. 43 renal transplant patients attending three renal transplantation centers, and 40 healthy ...201122089802
Kinetics of Effector Functions and Phenotype of Virus-Specific and ?d T Lymphocytes in Primary Human Cytomegalovirus Infection During Pregnancy.The T-cell response to human cytomegalovirus (HCMV) primary infection was analyzed in 27 pregnant women during the first year after primary HCMV infection. Pregnant women with remote HCMV infection were enrolled as controls. Interferon-?-producing T cells were readily detected at levels comparable (CD4(+)) or higher (CD8(+)) than controls, whereas the CD4(+) and CD8(+) lymphoproliferative response as well as IL-2 production was significantly reduced with respect to controls for at least 9 months ...201121847524
Blockade of Lyn kinase upregulates both canonical and non-canonical TLR-3 pathways in THP-1 monocytes exposed to human cytomegalovirus.Regulation of monocyte response to human cytomegalovirus (HCMV) occurs via activation of receptors that elicit innate antiviral effects and later T-cell responses. Our previous data (Yew et al.., 2010) demonstrated that human monocyte scavenger receptor A type 1 (SR-A1) are required for sensing of HCMV by endosomal toll-like receptors (TLRs)-3 and -9, which in turn induce critical pro-inflammatory cytokines. However, it remains unclear which subcellular molecules associated with SR-A1 lead to do ...201121978158
human cytomegalovirus induces mmp-1 and mmp-3 expression in aortic smooth muscle cells.human cytomegalovirus (hcmv) infection may be involved in the pathogenesis of atherosclerosis by modulating functions of smooth muscle cells (smc). in this study, we performed an oligonucleotide microarray screening of 780 inflammation-associated genes in hcmv-infected aortic smc (aosmc). the expression of 31 genes was stimulated and 24 genes were down-regulated following infection with hcmv strain dc-134. following infection with hcmv strain ad-169 infection, we found 24 genes to be stimulated ...201122207289
An artemisinin-derived dimer has highly potent anti-cytomegalovirus (CMV) and anti-cancer activities.We recently reported that two artemisinin-derived dimers (dimer primary alcohol 606 and dimer sulfone 4-carbamate 832-4) are significantly more potent in inhibiting human cytomegalovirus (CMV) replication than artemisinin-derived monomers. In our continued evaluation of the activities of artemisinins in CMV inhibition, twelve artemisinin-derived dimers and five artemisinin-derived monomers were used. Dimers as a group were found to be potent inhibitors of CMV replication. Comparison of CMV inhib ...201121904628
The Human Cytomegalovirus UL11 Protein Interacts with the Receptor Tyrosine Phosphatase CD45, Resulting in Functional Paralysis of T Cells.Human cytomegalovirus (CMV) exerts diverse and complex effects on the immune system, not all of which have been attributed to viral genes. Acute CMV infection results in transient restrictions in T cell proliferative ability, which can impair the control of the virus and increase the risk of secondary infections in patients with weakened or immature immune systems. In a search for new immunomodulatory proteins, we investigated the UL11 protein, a member of the CMV RL11 family. This protein famil ...201122174689
high-resolution human cytomegalovirus transcriptome.deep sequencing was used to bring high resolution to the human cytomegalovirus (hcmv) transcriptome at the stage when infectious virion production is under way, and major findings were confirmed by extensive experimentation using conventional techniques. the majority (65.1%) of polyadenylated viral rna transcription is committed to producing four noncoding transcripts (rna2.7, rna1.2, rna4.9, and rna5.0) that do not substantially overlap designated protein-coding regions. additional noncoding rn ...201122109557
progress in the development of new therapies for herpesvirus infections.resurgent interest in antiviral drugs for the treatment of herpesvirus has led to the development of new compounds that are progressing through clinical trials. this is important because there are few therapeutic options for resistant infections and some viruses such as human cytomegalovirus remain underserved. new compounds include conventional dna polymerase inhibitors such as valomaciclovir and cyclopropavir, as well as cmx001 that has a broad spectrum of antiviral activity that includes all ...201122162744
transcriptional features and transcript structure of ul145 in different strains of human cytomegalovirus.the human cytomegalovirus ul145 gene is located between the highly variable genes ul144 and ul146 in the ul/b' region. however, unlike its neighboring genes, ul145 is relatively conserved among strains isolated from patients. the transcriptional features and transcript structure of ul145 has not yet been examined. in this study, the transcriptional features and structure of ul145 were characterized using rna preparations from three hcmv strains isolated from patients, designated h, c, and x, res ...201122012723
the development of chinese specific human cytomegalovirus polyepitope recombinant vaccine.human cytomegalovirus (hcmv) infection is a major cause of morbidity in the recipients of organ transplants and in the congenitally infected infants. hcmv vaccine has emerged as an effective approach to prevent hcmv infection particularly for the development of multiple viral antigens vaccination and human leukocyte antigen (hla)-restricted polyepitope technology. as the chinese population makes up more than one fifth of the population worldwide, it is important to develop hcmv vaccines more spe ...201122197248
human cytomegalovirus primase ul70 specifically interacts with cellular factor snapin.genomic dna synthesis is a universally conserved process for all herpesviruses, including human cytomegalovirus (hcmv). hcmv ul70 is believed to encode the primase of the dna replication machinery, a function which requires localization in the nucleus, the site of viral dna synthesis. no host factors that interact with ul70 have been reported. in this study, we provide the first direct evidence that ul70 specifically interacts with snapin, a human protein that is predominantly localized in the c ...201121917956
[effects of allitridin on transcription of immediate-early, early and late genes of human cytomegalovirus in vitro].the effect of allitridin on the transcription levels of immediate-early (ie), early(e) and late (1) genes of human cytomegalovirus (hcmv) was investigated in order to explore the mechanism of allitridin against hcmv.201122016974
human cd1d molecules are resistant to human cytomegalovirus us2- and us11-mediated degradation.natural killer t (nkt) cells may play a crucial role in controlling viral infection by bridging the innate and adaptive immune systems. these cells are activated by lipids presented by cd1d molecules, which are structurally homologous to major histocompatibility complex class i (mhc-i) molecules. although human cytomegalovirus (hcmv) can avoid t cell recognition by down-regulating mhc-i-mediated antigen presentation, it remains unknown whether it can also interfere with cd1d-mediated lipid prese ...201121925141
Human cytomegalovirus US7 is regulated synergistically by two virally encoded microRNAs and by two distinct mechanisms.Human cytomegalovirus (HCMV) encodes at least 14 microRNAs (miRNAs) that act posttranscriptionally to repress gene expression. Although several HCMV miRNA targets of both cellular and viral origin have been identified, our knowledge of their function remains limited. HCMV miRNA targets, as well as phenotypes associated with HCMV miRNA mutants, have been difficult to identify since the downregulation of targets by a single miRNA is often less than 2-fold. Several factors can contribute to the str ...201121900172
[MicroRNA expression profile and pathogenetic initial study in essential hypertension].To study the differential microRNAs expression between patients with essential hypertension and healthy controls.201121924071
direct inhibitory effects of ganciclovir on icam-1 expression and proliferation in human coronary vascular cells (si/mpl-ratio: >1).treatment of the human cytomegalovirus (hcmv) infection with ganciclovir has beneficial indirect effects on the complex interactions of hcmv with restenosis, atherosclerosis, and transplant vascular sclerosis. the current study reports on direct effects of ganciclovir on expression of icam-1 and cell proliferation, key events of coronary atherosclerosis/restenosis. a potential clinical relevance of the data will be evaluated with the help of si/mpl-ratio's.201121169918
seroprevalence and serum profile of cytomegalovirus infection among patients with hematologic disorders in bahia state, brazil.human cytomegalovirus (cmv) is a ubiquitous herpesvirus with from 30% to 100% of the general population exhibiting prior exposure by serology. this cross-sectional study evaluated the serological profile of anti-cmv antibodies and two acute-phase reaction proteins in haematologic disorder patients (hdps) from bahia state, brazil. immuno-chemiluminescence assays were performed to detect anti-cmv igm and igg antibodies. serological levels of high sensitivity c-reactive protein (crph) and alpha-1-a ...201121181926
characterization of 3' termini of human cytomegalovirus ul138-ul145 transcripts in a clinical strain.the functions of some proteins encoded by human cytomegalovirus (hcmv) ul/b' genes have been studied; however, systematic analysis of the transcripts for this region is still insufficient. the results of both rapid amplification of cdna ends (race) and cdna library screening in this study proved that 3' termini of all transcripts in the ul138-ul145 region were located approximately 20 bp downstream from each potential poly (a) signal, which were at the positions of nucleotides 7184, 9954 and 128 ...201121204946
a rapid method to screen putative mrna targets of any known microrna.micrornas (mirnas) are a group of regulatory rnas that regulate gene expression by binding to specific sequences on target mrnas. however, functional identification of mrna targets is usually difficult and time consuming. here we report hybrid-pcr as a new and rapid approach to screen putative mrna targets in vitro.201121219658
human cytomegalovirus ul97 kinase and nonkinase functions mediate viral cytoplasmic secondary envelopment.previous studies have revealed critical roles for the human cytomegalovirus (hcmv) ul97 kinase in viral nuclear maturation events. we have shown recently that ul97 affects the morphology of the viral cytoplasmic assembly compartment (ac) (m. azzeh, a. honigman, a. taraboulos, a. rouvinski, and d. g. wolf, virology 354:69-79, 2006). here, we employed a comprehensive ultrastructural analysis to dissect the impact of ul97 on cytoplasmic steps of hcmv assembly. using ul97 deletion (?ul97) and kinase ...201121248036
exploitation of herpesviral transactivation allows quantitative reporter gene-based assessment of virus entry and neutralization.herpesviral entry is a highly elaborated process requiring many proteins to act in precise conjunction. neutralizing antibodies interfere with this process to abrogate viral infection. based on promoter transactivation of a reporter gene we established a novel method to quantify herpesvirus entry and neutralization by antibodies. following infection with mouse and human cytomegalovirus and herpes simplex virus 1 we observed promoter transactivation resulting in substantial luciferase expression ...201121264213
cytomegalovirus capsid protease: biological substrates are cleaved more efficiently by full-length enzyme (pul80a) than by the catalytic domain (assemblin).we compared the full-length capsid maturational protease (ppr, pul80a) of human cytomegalovirus with its proteolytic domain (assemblin) for the ability to cleave two biological substrates, and we found that ppr is more efficient with both. affinity-purified, refolded enzymes and substrates were combined under defined reaction conditions, and cleavage was monitored and quantified following staining of the resulting electrophoretically separated fragments. the enzymes were stabilized against self- ...201121270147
isolation and characterization of cynomolgus macaque (macaca fascicularis) cytomegalovirus (cycmv).cynomolgus macaques have been widely used as an animal model in preclinical biomedical research and are becoming more popular among hiv/siv vaccine researchers. here we report the isolation and characterization of a cytomegalovirus from cynomolgus macaques (cycmv). cycmv was isolated from a healthy captive-bred 4-year-old cynomolgus macaque of filipino origin. the virus was identified by its characteristic growth properties in cell culture, ultrastructural morphology and sequence of viral dna po ...201121272907
inhibition of mouse tap by immune evasion molecules encoded by non-murine herpesviruses.herpesviruses escape elimination by cytotoxic t lymphocytes through specific interference with the antigen-presenting function of mhc class i (mhc i) molecules. the transporter associated with antigen processing (tap) forms a bottleneck in the mhc i antigen presentation pathway. the fact that multiple viruses, especially herpesviruses, encode molecules blocking tap function is a case in point. the action of these viral immuno evasins is usually potent and very specific, making these proteins val ...201121292324
a dominant role for the immunoproteasome in cd8+ t cell responses to murine cytomegalovirus.murine cytomegalovirus (mcmv) is an important animal model of human cytomegalovirus (hcmv), a ß-herpesvirus that infects the majority of the world's population and causes disease in neonates and immunocompromised adults. cd8(+) t cells are a major part of the immune response to mcmv and hcmv. processing of peptides for presentation to cd8(+) t cells may be critically dependent on the immunoproteasome, expression of which is affected by mcmv. however, the overall importance of the immunoproteasom ...201121304910
the human cytomegalovirus trl11/irl11-encoded fc?r binds differentially to allelic variants of immunoglobulin g1.human cytomegalovirus (hcmv) has evolved several immune-evasion strategies. one strategy involves encoding fcgamma receptor (fc?r)-like proteins that thwart the fc?-mediated effector functions. our aim was to determine whether gm allotypes-immunoglobulin ? chain determinants expressed primarily on the fc segment-modulate this viral strategy through differential binding to the viral fc?r. results of our elisa binding studies show that the mean absorbance values for binding to the hcmv trl11/irl11 ...201121311920
prospective comparison of pcr-based vs late mrna-based preemptive antiviral therapy for hcmv infection in patients after allo-sct.human cmv (hcmv)-directed preemptive therapy has helped to improve the outcome following allo-sct. in this study, we evaluated the safety and efficacy of a late mrna-based (nuclisens cmv pp67) anti-hcmv treatment strategy. a prospective randomized multicenter pilot trial was performed comparing pcr-based, with late mrna-based preemptive hcmv-directed antiviral therapy in patients after allo-sct. in all, 133 patients were randomized in three different centers at the time of transplant, 130 of who ...201120581879
Mutational Mapping of pUL131A of Human Cytomegalovirus Emphasizes Its Central Role for Endothelial Cell Tropism.The UL131A protein is part of a pentameric variant of the gcIII complex in the virion envelope of human cytomegalovirus (HCMV), which has been found essential for efficient entry into endothelial cells (ECs). Using a systematic mutational scanning approach, we aimed to define peptide motifs within the UL131A protein that contribute to EC infection. Mutant viruses were generated in which charged amino acids within frames of 2 to 6 amino acids were replaced with alanines. The resulting viruses wer ...201222031943
in this issue.cover image: the cover is based on a spinal cord histology section taken from a tnfr2(-/-) mouse adoptively transferred with tnfr2(-/-) treg cells prior to immunization with mog(35-55) to induce eae. the section is stained with luxol fast blue to detect demyelination; luxol fast red, which detects inflammatory infiltration, is the counterstain. the image is taken from the article by tsakiri et al. (pp. 403-412) in which it is shown that tnfr2 on non-haematopoietic cells is necessary for treg- ...201222266713
human cytomegalovirus infection induces adipocyte-like lipogenesis through activation of sterol regulatory element binding protein 1.sterol regulatory element binding proteins (srebps) are essential transcriptional factors that control expression of lipogenic genes and adipocyte differentiation. hcmv infection has been shown to require the induction of lipogenesis. here we show that the induction of lipogenesis and the expression of key lipogenic enzymes in human fibroblasts occurs by 24 hours post-hcmv infection. this activation correlates with increased cleavage of the srebp1 precursors to form the mature active transcripti ...201222258239
High-Resolution Profiling and Analysis of Viral and Host Small RNAs during Human Cytomegalovirus Infection.Human cytomegalovirus (HCMV) contributes its own set of microRNAs (miRNAs) during lytic infection of cells, likely fine-tuning conditions important for viral replication. To enhance our understanding of this component of the HCMV-host transcriptome, we have conducted deep-sequencing analysis of small RNAs (smRNA-seq) from infected human fibroblast cells. We found that HCMV-encoded miRNAs accumulate to ~20% of the total smRNA population at late stages of infection, and our analysis led to improve ...201222013051
host and viral traits predict zoonotic spillover from mammals.the majority of human emerging infectious diseases are zoonotic, with viruses that originate in wild mammals of particular concern (for example, hiv, ebola and sars). understanding patterns of viral diversity in wildlife and determinants of successful cross-species transmission, or spillover, are therefore key goals for pandemic surveillance programs. however, few analytical tools exist to identify which host species are likely to harbour the next human virus, or which viruses can cross species ...201728636590
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