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the products of human cytomegalovirus genes ul23, ul24, ul43 and us22 are tegument components.we have investigated the human cytomegalovirus (hcmv) us22 gene family members ul23, ul24, ul43 and us22. specific antibodies were generated to identify pul23 (33 kda), pul24 (40 kda) and pul43 (48 kda), while pus22 was identified by monoclonal antibody hwlf1. a c-terminally truncated ul43 product (pul43t; 21 kda) produced by a deletion mutant was also investigated. the ul24 and ul43 genes were expressed with early-late (gamma1) and true-late (gamma2) kinetics, respectively. immunoblot and immun ...200212029146
plasmid mediated expression of human growth hormone increases splenocytes proliferative response in vivo.as far as a physiological state of immune system cells is of great importance, for the investigation of the growth hormone influence on spleen t-lymphocytes ability to divide, we utilised plasmid-mediated gene transfer of hgh cdna regulated by a powerful human cytomegalovirus immediate-early (cmv-ie) enhancer-promoter. the femur muscles of mice were injected with 50 mg of the plasmid dna and then electrostimulated. 7 days later muscle tissues were harvested, and hgh dna and rna presence were pro ...200112035549
mechanisms of human cytomegalovirus persistence and latency.human cytomegalovirus (hcmv) is a ubiquitous beta-herpesvirus that causes severe disease primarily in immunosuppressed individuals. a major characteristic of hcmv with obvious clinical importance is the ability of the virus to establish lifelong infection within the host following the initial acute infection. one strategy used by hcmv to maintain itself within the host is the establishment of cellular sites of persistent infection and viral latency. recent studies have identified endothelial cel ...200212045013
identification of hla-a24-restricted ctl epitope encoded by the matrix protein pp65 of human cytomegalovirus.the activation of a specific cellular immune response against human cytomegalovirus (cmv) is an important key factor to solving cmv infection after bone marrow transplantation (bmt). in the present study, our purpose was to identify the hla-a24-restricted cytotoxic t cell (ctl) epitope from the cmv immunogenic matrix protein pp65. we selected five cmv pp65 peptides with hla-a24 binding motif from the hla peptide binding predictions web site. peptide binding assay was performed using biotinylated ...200212057851
dual regulatory role of human cytomegalovirus immediate-early protein in il1b transcription is dependent upon spi-1/pu.1.activation of il1b gene transcription has been shown to play a crucial role in human cytomegalovirus (hcmv) infection. we previously reported that hcmv immediate-early (ie) proteins vigorously transactivate il1b expression without the need for a normally essential upstream enhancer. this activation appears to depend upon protein-protein tethering between ie2, which provides a transcription activation domain (tad), and the dna-binding domain of the transcription factor spi-1. we now show a distin ...200212061786
in vitro antiviral efficacy of the ganciclovir complexed with beta-cyclodextrin on human cytomegalovirus clinical strains.the toxicity of the compounds currently used in the treatment of human cytomegalovirus (hcmv) infections in immunocompromised hosts may force the treatment to be discontinued. the aim of this study was to improve the antiviral activity of ganciclovir (gcv), one the most widely used drug, by complexing it with beta-cyclodextrin. cyclodextrins (cds) have the property to form inclusion complexes with a great number of molecules and to enhance bioavailability and biological properties of these molec ...200212062397
human cytomegalovirus perinatal infections in a tertiary care setting. 200212084950
functional expression of chitinase and chitosanase, and their effects on morphologies in the yeast schizosaccharomyces pombe.the chitinase a (chia) gene from enterobacter sp. g-1 and the chitosanase a (choa) gene from matsuebacter chitosanotabidus 3001 were expressed separately and simultaneously in the yeast schizosaccharomyces pombe. the chia gene was placed under the transcriptional control of the nmt1 promoter with the glutathione s transferase (gst), and the choa gene was expressed by the human cytomegalovirus (hcmv) promoter with the p factor secretion signal (p3). the expressed proteins of choa and gst-chia wer ...200212092833
experimental coinfection of rhesus macaques with rhesus cytomegalovirus and simian immunodeficiency virus: pathogenesis.human cytomegalovirus (hcmv) possesses low pathogenic potential in an immunocompetent host. in the immunosuppressed host, however, a wide spectrum of infection outcomes, ranging from asymptomatic to life threatening, can follow either primary or nonprimary infection. the variability in the manifestations of hcmv infection in immunosuppressed individuals implies that there is a threshold of host antiviral immunity that can effectively limit disease potential. we used a nonhuman primate model of c ...200212097580
construction and characterization of recombinant adenoviruses expressing biologically active human brain-derived neurotrophic factor and neurotrophin-3.in order to deliver brain-derived neurotrophic factor(bdnf) and neurotrophin-3(nt3) into cns to prevent or reduce degeneration of cns neurons in human neurodegenerative diseases and neuron injuries, recombinant adenoviruses ad-bdnf and ad-nt3 were constructed. bdnf and nt3 genes were inserted into an e1-substituted adenovirus shuttle plasmid, respectively, and were driven by the human cytomegalovirus immediate-early gene promoter/enhancer. after cotransfection into 293 cells with the adenovirus ...200012098787
recombinant full-length human cytomegalovirus protease has lower activity than recombinant processed protease domain in purified enzyme and cell-based assays.herpesviruses encode a protease that is essential for virus replication. the protease undergoes cleavage to a processed form during capsid maturation. a recombinant 75 kda form of the protease from human cytomegalovirus was purified and compared with the recombinant 29 kda processed form. modification with an active site titrant suggested that most of each recombinant protease preparation was active (66 and 86%, respectively). protease activity was compared using a low-molecular weight peptide s ...200212103430
immunomodulation by cytomegaloviruses: manipulative strategies beyond evasion.human cytomegalovirus (cmv) remains the major infectious cause of birth defects as well as an important opportunistic pathogen. individuals infected with cmv mount a strong immune response that suppresses persistent viral replication and maintains life-long latency. loss of immune control opens the way to virus reactivation and disease. the large number of immunomodulatory functions encoded by cmv increases the efficiency of infection, dissemination, reactivation and persistent infection in host ...200212110212
immunoelectron microscopy analysis of hcmv gpul73 (gn) localization.human cytomegalovirus (hcmv) ul73 encodes for a polymorphic structural glycoprotein, gpul73(gn), conserved among herpesviruses. this study analyzed the intracellular and intraviral localization of gpul73 by immunoelectron-microscopy comparing the reactivity of two different antibodies. we found that gn is an envelope component of the mature viral particle with at least a portion exposed at the virus surface and another at the internal side of the envelope. furthermore, gpul73 is also present in ...200212111433
preclinical and toxicology studies of 1263w94, a potent and selective inhibitor of human cytomegalovirus replication.1263w94 is a novel benzimidazole compound being developed for treatment of human cytomegalovirus infection. no adverse pharmacological effects were demonstrated in safety pharmacology studies with 1263w94. the minimal-effect dose in a 1-month rat study was 100 mg/kg/day, and the no-effect dose in a 1-month monkey study was 180 mg/kg/day. toxic effects were limited to increases in liver weights, neutrophils, and monocytes at higher doses in female rats. 1263w94 was not genotoxic in the ames or mi ...200212121907
the attenuated towne strain of human cytomegalovirus may revert to both endothelial cell tropism and leuko- (neutrophil- and monocyte-) tropism in vitro.the towne strain of human cytomegalovirus (hcmv), originally recovered from the urine of a congenitally infected newborn, was attenuated through 125 passages in human embryonic lung fibroblast cell cultures. although reliable markers of attenuation were not identified, the virus was shown to be attenuated by inoculation of both healthy human volunteers and immunocompromised patients. more recently, towne (like other laboratory-adapted strains) was shown not to have two biological properties typi ...200212124463
human adenovirus and human cytomegalovirus infections in preterm newborns: no association with bronchopulmonary dysplasia.connatal infection with human adenovirus (hadv) has been recently proposed as a cofactor for the development of bronchopulmonary dysplasia (bpd) in preterm infants [couroucli et al. 2000 pediatr res 47:225-232]. in another study, bpd was associated with an increased incidence of human cytomegalovirus (hcmv) infection [sawyer et al. 1987 am j dis child 141:303-305]. during a 18-mo study period, we investigated tracheal aspirates or pharyngeal aspirates and urine samples collected during the first ...200212149499
high frequency of human cytomegalovirus (hcmv)-specific cd8+ t cells detected in a healthy cmv-seropositive donor.human cytomegalovirus (hcmv) persists after infection but is controlled by cellular immune responses, particularly by cd8+ t cells. if infected individuals are immunosuppressed, hcmv can be reactivated. upon testing the blood of healthy donors with human lymphocyte antigen tetramers, we found one individual with about 50% of his cd8+ t cells being specific for the immunodominant pp65 epitope nlvpmvatv over a period of 2 years the high level of hcmv-specific t cells was maintained, and no hcmv dn ...200212169019
role of the human herpesvirus 6 u69-encoded kinase in the phosphorylation of ganciclovir.the human herpesvirus 6 (hhv-6) u69 gene product (pu69) is the presumed functional homolog of the human cytomegalovirus (hcmv) ul97-encoded kinase (pul97), which converts ganciclovir to its monophosphate metabolite in hcmv-infected cells. it has been reported that insertion of u69 into baculovirus confers sensitivity to ganciclovir in insect cells (j virol 73:3284-3291, 1999). our metabolic studies in hhv-6-infected human t-lymphoblast cells indicated that the efficiency of ganciclovir phosphory ...200212181449
2-chloro-3-pyridin-3-yl-5,6,7,8-tetrahydroindolizine-1-carboxamide (cmv423), a new lead compound for the treatment of human cytomegalovirus infections.human cytomegalovirus (hcmv) remains one of the major pathogens in immunocompromised patients (aids and transplants) and the main cause for congenital infections leading from slight cognitive defects up to severe mental retardation. the drugs that are currently available for the treatment of hcmv infections, i.e. ganciclovir, foscarnet and cidofovir, are all acting at the level of the viral dna polymerase. here we describe an entirely new molecule, the 2-chloro-3-pyridin-3-yl-5,6,7,8-tetrahydroi ...200212206879
inhibition of the mhc class ii antigen presentation pathway by human cytomegalovirus.human cytomegalovirus (hcmv) causes serious disease in immunocompromised individuals. normally, anti-hcmv immune response controls virus replication following reactivation from latency. however, hcmv, like other large herpesviruses, encodes immune evasion proteins that allow the virus to replicate, for a time or in specific tissues, and produce viral progeny in the face of robust host immunity. hcmv glycoproteins us2, us3, us6 and us11 all inhibit different stages of the mhc class i antigen pres ...200212224504
herpes viral proteins blocking the transporter associated with antigen processing tap--from genes to function and structure.in adaptation to the immune system, viruses have developed manifold mechanisms to evade the immune response, causing lifelong persistence in the host. several members of the herpesvirus family are known to interfere with antigen presentation via mhc class i molecules. here we compare the mechanistic and structural aspects of two unrelated herpesviral proteins, both of which have selected the transporter associated with antigen processing (tap) as target for immune evasion. however, icp47 (ie12) ...200212224518
application of a 5-bromo-2'-deoxyuridine elisa for measuring the lymphoproliferative response to human cytomegalovirus in hiv-1-infected patients.assessment of the lymphoproliferative response to human cytomegalovirus (hcmv) may help to identify human immunodeficiency virus (hiv)-1-infected patients at high risk of developing hcmv end-organ disease. the tritiated thymidine ([3h]-tdr)-incorporation assay is the gold standard for measuring lymphoproliferative responses, though it is unsuitable as a routine laboratory procedure. an alternative non-radioactive technique, a 5-bromo-2'-deoxyuridine (brdu) enzyme-linked immunosorbent assay, was ...200212270657
human cytomegalovirus immediate-early protein ie2-86, but not ie1-72, causes graft coronary arteriopathy in the transplanted rat heart.graft coronary arteriopathy (gca) after heart transplantation is a major factor limiting the long-term survival of the recipients. human cytomegalovirus (hcmv) infection is a possible cause of this disease which is characterized by diffuse intimal thickening resulting from smooth muscle cell migration and proliferation. it has been reported that hcmv immediate-early (ie) proteins, ie1 and ie2, could play an important role in the development of this disease; however, the precise in vivo role of t ...200212354726
analysis of human cytomegalovirus us3 gene products.similar to other herpesviruses, human cytomegalovirus remains in the infected host following resolution of the primary infection. the ability to persist in the host after primary infection is believed to be strongly influenced by the ability of hcmv to down-regulate immune recognition of infected cells. one of the genes contributing to immune evasion is the us3 gene. the us3 gene has been shown to retain major histocompatibility complex type i molecules in the endoplasmic reticulum. the us3 gene ...200212359444
development of novel vaccine strategies against human cytomegalovirus infection based on subviral particles.pre- and perinatal human cytomegalovirus (hcmv) infection remains one of the major causes of mental defects and sensineural hearing loss in children. in addition, it is a prominent infectious complication in immunosuppressed individuals such as aids patients or transplant recipients. therefore, the development of an hcmv vaccine has been given top priority by health care institutions.200212361759
human cytomegalovirus-caused damage to placental trophoblasts mediated by immediate-early gene-induced tumor necrosis factor-alpha.infection of the fetal epithelium (trophoblast) lining the villous placenta by human cytomegalovirus (hcmv) accompanies placental inflammations and fetal intrauterine growth restriction. however, the consequences of infection on the villous trophoblast have not been explored. we show that hcmv infection of primary immature (cytotrophoblast-like) or mature (syncytiotrophoblast-like) cultures results in loss of half of the cells within 24 hours of virus challenge. two-color immunofluorescence of h ...200212368210
the genes encoding the gciii complex of human cytomegalovirus exist in highly diverse combinations in clinical isolates.the ul74 (glycoprotein o [go])-ul75 (gh)-ul115 (gl) complex of human cytomegalovirus (cmv), known as the gciii complex, is likely to play an important role in the life cycle of the virus. the gh and gl proteins have been associated with biological activities, such as the induction of virus-neutralizing antibody, cell-virus fusion, and cell-to-cell spread of the virus. the sequences of the two gh gene variants, readily recognizable by restriction endonuclease polymorphism, are well conserved amon ...200212368327
inhibition of hla-dr assembly, transport, and loading by human cytomegalovirus glycoprotein us3: a novel mechanism for evading major histocompatibility complex class ii antigen presentation.human cytomegalovirus (hcmv) establishes persistent lifelong infections and replicates slowly. to withstand robust immunity, hcmv utilizes numerous immune evasion strategies. the hcmv gene cassette encoding us2 to us11 encodes four homologous glycoproteins, us2, us3, us6, and us11, that inhibit the major histocompatibility complex class i (mhc-i) antigen presentation pathway, probably inhibiting recognition by cd8(+) t lymphocytes. us2 also inhibits the mhc-ii antigen presentation pathway, causi ...200212368336
isolation and expansion of human cytomegalovirus- specific cytotoxic t lymphocytes using interferon-gamma secretion assay.the aim of this study was to isolate and expand donor-derived human cytomegalovirus (hcmv)-specific cytotoxic t lymphocytes (ctls) for adoptive transfer of 10(7) cells per m(2) of body surface area to restore protective immunity after stem cell transplantation.200212384149
crystal structure of lir-2 (ilt4) at 1.8 a: differences from lir-1 (ilt2) in regions implicated in the binding of the human cytomegalovirus class i mhc homolog ul18.leukocyte immunoglobulin-like receptor-1 (lir-1) and lir-2 (also known as ilt2 and ilt4 respectively) are highly related cell surface receptors that bind a broad range of class i mhc molecules with low (microm) affinities. expressed on monocytic cells and macrophages, both molecules transmit inhibitory signals after binding ligands. in addition to binding host class i mhc, the lir-1 molecule, which is also expressed on lymphoid tissues, binds with a high (nm) affinity to ul18, a class i mhc homo ...200212390682
antiviral activity of spirulina maxima against herpes simplex virus type 2.spirulina has been used in a variety of practical applications in biotechnology and medical sciences. this paper presents the antiviral activity found in a hot water extract (hwe) of a commercial preparation of spirulina maxima, studied by a microplate inhibition assay, using several viruses. the hwe inhibited the infection for: herpes simplex virus type 2 (hsv-2), pseudorabies virus (prv), human cytomegalovirus (hcmv), and hsv-1, and the 50% effective inhibition doses (ed(50)) were 0.069, 0.103 ...200212406511
expression from second-generation feline immunodeficiency virus vectors is impaired in human hematopoietic cells.vectors based on the feline immunodeficiency virus (fiv) have been developed as an alternative to those based on another lentivirus, human immunodeficiency virus-1 (hiv-1), because of theoretical safety advantages. we compared the efficiency of gene transfer and expression in human and feline hematopoietic progenitors using second-generation hiv-1 and fiv-based vectors. vector pairs were tested using either human cytomegalovirus or murine phospho-glycerate kinase (pgk) internal promoters and wer ...200212409263
human cytomegalovirus dna in plasma and serum specimens of renal transplant recipients is highly fragmented.quantitation of cytomegalovirus (cmv) dna in plasma and serum by pcr is increasingly used to identify patients at risk for developing cmv disease and to monitor the efficacy of antiviral therapy. although cmv dna levels are generally interpreted as viral loads, the exact nature of the viral dna in these specimens is unknown. we studied the state of cmv dna in plasma and serum specimens obtained from three renal transplant recipients at peak viral dna levels during primary cmv infection. for this ...200212409382
relationship between autophosphorylation and phosphorylation of exogenous substrates by the human cytomegalovirus ul97 protein kinase.human cytomegalovirus encodes an unusual protein kinase, ul97, which is a member of the hvu(l) family of protein kinases encoded by diverse herpesviruses. ul97 is able to autophosphorylate and to phosphorylate certain exogenous substrates, including nucleoside analogs such as ganciclovir. it has previously been concluded that phosphorylation of ul97 is essential for its phosphorylation of ganciclovir. we examined the relationship between autophosphorylation of ul97 and its activity on exogenous ...200212414936
cytomegalovirus infection in pregnancy.to investigate the effects of intrauterine human cytomegalovirus (hcmv) infection on pregnancy outcomes and infant development.200212427394
upregulation of cd40 expression on endothelial cells infected with human cytomegalovirus.cd40 has been identified as an important molecule for a number of processes, such as immune responses, inflammation, and the activation of endothelia. we investigated cd40 in endothelial cells (ec) following infection with an endotheliotropic strain of human cytomegalovirus (hcmv). between 8 and 72 h postinfection, we observed a significant increase in cd40 levels on the surface of infected ec, as measured by fluorescence-activated cell sorting analysis. as a consequence of cd40 upregulation, in ...200212438605
polysulfonates derived from metal thiolate complexes as inhibitors of hiv-1 and various other enveloped viruses in vitro.sodium 2-mercaptoethanesulfonate reacts with the metal ions pd(ii), pt(ii), ag(i), cd(ii) and zn(ii) to yield complexes containing multiple anionic sulfonate sites. on the basis of spectroscopic and other analytical data the complexes were assigned the tentative molecular formulas: pd6(sch2ch2so3na)12, ptn(sch2ch2so3na)2n+2, agn(sch2ch2so3na)n, na2zn4(sch2ch2so3na)10, and na2cd4(sch2ch2so3na)10. the complexes displayed a variety of differences in activity towards dna and rna viruses. the platinu ...200212448691
donor-derived circulating endothelial cells after kidney transplantation.in solid-organ transplantation, the allograft vasculature, in particular the endothelium, is prone to injury inflicted by peritransplantational and posttransplantational factors. previously, we have shown that circulating endothelial cells (cec) can be detected in the peripheral blood of kidney allograft recipients and are often associated with acute rejection and active infections with human cytomegalovirus. in the present study we hypothesized that cec after kidney transplantation are of donor ...200212451273
nf-kappab--a potential therapeutic target for inhibition of human cytomegalovirus (re)activation?from clinical studies the proinflammatory cytokine tnfalpha was proposed to play a key role in human cytomegalovirus (hcmv) reactivation from latency. in vitro experiments confirmed that tnfalpha stimulates the activity of the hcmv ie1/2 enhancer/promoter, which controls immediate early protein ie1 and ie2 gene expression via activation of the transcription factor nf-kappab and its binding to putative binding sites in the ie1/2 enhancer. nf-kappab was also proposed to be involved in ie1-mediated ...200212452437
a single viral protein hcmv us2 affects antigen presentation and intracellular iron homeostasis by degradation of classical hla class i and hfe molecules.hfe is a nonclassical class i molecule that associates with beta 2-microglobulin (beta 2m) and with the transferrin receptor. hfe accumulates in transferrin-containing endosomes, and its overexpression in human cell lines correlates with decreased transferrin receptor (tfr)-mediated iron uptake and decreased intracellular iron pools. a mutation that interferes with proper folding and assembly of hfe complexes results in a severe iron-overload disease hereditary hemochromatosis. we previously sug ...200312456502
human cytomegalovirus load in various body fluids of congenitally infected newborns.congenital human cytomegalovirus (hcmv) infection is the most common intrauterine viral disease in western countries. little is known about hcmv virus load in various body fluids of congenitally infected children.200212467781
human cytomegalovirus infection reduces surface ccr5 expression in human microglial cells, astrocytes and monocyte-derived macrophages.within the brain, glial cells are target cells for human cytomegalovirus (hcmv) and hiv. we infected cultures of unstimulated human microglial cells and astrocytes of embryonic origin and of monocyte-derived macrophages (mdm) with hcmv strain ad169 and observed down-regulation of the plasma membrane expression of ccr5 in the three cell types, and of cxcr4 and cd4 in microglial cells only. cells were then coinfected simultaneously or at a 24-h interval with both ad169 and two different hiv-1 mono ...200212475630
role of cidofovir in the treatment of dna virus infections, other than cmv infections, in immunocompromised patients.cidofovir is a nucleotide analog marketed for the treatment of human cytomegalovirus infections in immunocompromised patients. an increasing number of reports have appeared on the use of cidofovir for the treatment of other severe dna virus infections in immunocompromised patients. the activity of cidofovir against herpes simplex viruses resistant to classic (acyclovir and/or foscavir) therapy has been widely documented. cidofovir has also been used for the treatment of other herpesvirus infecti ...200212476953
human cytomegalovirus vaccine is an orphan. 200212477309
nk cell-mediated lysis of autologous hcmv-infected skin fibroblasts is highly variable among nk cell clones and polyclonal nk cell lines.lysis of human cytomegalovirus (hcmv)-infected fibroblasts by autologous natural killer (nk) cells was examined in vitro. for nk cell clones, receptor expression was determined at the level of mrna and cell-surface protein and compared to the lysis of hcmv ad169 strain-infected fibroblasts in which hla class i was >70% downregulated. the clones ranged broadly in their ability to lyse ad169-infected fibroblasts, correlating neither with the expression of inhibitory kir, leukocyte inhibitory recep ...200212482387
cytomegalovirus periodontal presence is associated with subgingival dialister pneumosintes and alveolar bone loss.destructive periodontal disease is associated with human cytomegalovirus (hcmv), epstein-barr type 1 virus (ebv-1) and other members of the herpesviridae family as well as with various gram-negative anaerobic bacteria, including the dialister pneumosintes species. this study aimed to determine possible interrelationships between periodontal hcmv, ebv-1, herpes simplex virus and d. pneumosintes, and relate the microbiological findings to periodontitis clinical status. sixteen subjects each contri ...200212485328
[relationship of nitric oxide with intrauterine human cytomegalovirus active infection during early pregnancy].to study the relationship of nitric oxide (no) with intrauterine human cytomegalovirus (hcmv) active infection during early pregnancy.200212487920
the human cytomegalovirus ul97 protein kinase, an antiviral drug target, is required at the stage of nuclear egress.human cytomegalovirus encodes an unusual protein kinase, ul97, that activates the established antiviral drug ganciclovir and is specifically inhibited by a new antiviral drug, maribavir. we used maribavir and a ul97 null mutant, which is severely deficient in viral replication, to determine what stage of virus infection critically requires ul97. compared with wild-type virus, there was little or no decrease in immediate-early gene expression, viral dna synthesis, late gene expression, or packagi ...200312502806
human cytomegalovirus and immunopathology. 200212503063
tn7-mediated introduction of dna sequences into bacmid-cloned cytomegalovirus genomes for rapid recombinant virus construction.our basic understanding of how viruses infect, replicate, and cause disease has been largely derived from genetic approaches in which viral sequences have been mutated and the consequences of those mutations determined. in the herpesvirus field, deletions or insertions that preclude expression of specific viral proteins or remove critical cis elements have been invaluable in identifying their overall functions. we are now ready to move to a new level of detail-mapping functional domains within v ...200312505633
[amino acid sequence analysis of peptides that can react to the nuclear localization signals of human cytomegalovirus ppul44].to find the peptides that have strong binding ability to the nuclear localization signals (nls) of human cytomegalovirus (hcmv) ppul44 protein, and to analyze their amino acid sequences.200112526308
down-regulation of surface major histocompatibility complex class i by guinea pig cytomegalovirus.live attenuated strains of human cytomegalovirus are under development as vaccines to prevent birth defects resulting from congenital infections. these strains encode four proteins that inhibit surface expression of mhc class i, presumably to evade cytotoxic t-cell recognition and, perhaps, attenuate induction of immunity. to initiate studies of the role of class i down-regulation on congenital infection and vaccine efficacy, the ability of guinea pig cytomegalovirus to down-regulate class i was ...200312533702
the interaction between the major capsid protein and the smallest capsid protein of human cytomegalovirus is dependent on two linear sequences in the smallest capsid protein.the assembly of human cytomegalovirus (hcmv) with recombinant systems has not been accomplished. an understanding of specific interactions between individual capsid proteins could point to unique characteristics of the assembly process of hcmv capsids. similar to its herpes simplex virus counterpart, vp26 (ul35), the hcmv smallest capsid protein (scp; ul48/49) decorates hexons in the mature capsid. in contrast to vp26, the hcmv scp is essential for virus assembly. in this study we have shown tha ...200312552013
[the experimental and clinical study of inhibitory effects of re-du-qing on human cytomegalovirus (hcmv)].to study the theurapeutic effect of chinese medicine re-du-qing on hcmv.199912569789
porcine cytomegalovirus in pigs being bred for xenograft organs: progress towards control.in human medicine, human cytomegalovirus (hcmv) is readily transmitted by organ transplant causing end-organ disease and triggering graft rejection in recipients. because of a chronic shortage of human organs, pigs transgenic for human complement control proteins are being considered as potential donors. such xenotransplantation raises concerns about the potential zoonotic transmission of viruses including porcine cytomegalovirus (pcmv), an endemic infection of pigs. similar to hcmv and pcmv tra ...200312588647
multiple relapses of human cytomegalovirus retinitis during haart in an aids patient with reconstitution of cd4+ t cell count in the absence of hcmv-specific cd4+ t cell response.while in the past human cytomegalovirus (hcmv) represented the major viral opportunistic pathogen in patients with aids, incidence of hcmv disease in hiv-infected patients drastically dropped after introduction of highly active antiretroviral therapy (haart). however, cases of hcmv disease in hiv-infected patients treated with haart have been reported.200312589839
herpesviruses: emerging nosocomial pathogens?herpesviruses are ubiquitous pathogens that are known to cause infection in humans and animals. it is likely that more than 90% of adults have been infected by one or more herpesviruses. as hospitalized patients become increasingly immunosuppressed by virtue of illness or therapies, it is increasingly likely that human herpesvirus infection will become manifest in the hospital. whether these manifestations represent manifestations of reactivated latent disease or true nosocomial infections is an ...200112594867
mutations conferring foscarnet resistance in a cohort of patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis.the clinical significance of cytomegalovirus (cmv) foscarnet resistance was studied in patients with acquired immunodeficiency syndrome and cmv retinitis. sequencing of the cmv pol gene was performed in 30 isolates. phenotypic resistance was characterized by the dna hybridization assay (dha) in 30 isolates and by plaque-reduction assay (pra) in 18 isolates. nine isolates had foscarnet resistance mutations, including v787l and e756q that were confirmed by marker transfer experiments. seven of 9 i ...200312599051
inter- and intragenic variations complicate the molecular epidemiology of human cytomegalovirus.human cytomegalovirus isolates were analyzed, both by restriction fragment-length polymorphism typing and by sequencing for intra- and intergenic variability at 9 sites on the genome, to determine whether genetic variation influenced disease outcome and whether linkage among genes could be identified. variation at the ul55 (glycoprotein b [gb]), ul74 (go), ul75 (gh), ul115 (gl), us9, and us28 gene open-reading frames was studied in relationship to outcome of cytomegalovirus disease. major findin ...200312599055
human cytomegalovirus protein pp65 mediates accumulation of hla-dr in lysosomes and destruction of the hla-dr alpha-chain.human cytomegalovirus (hcmv) has developed multiple strategies to escape immune recognition. here, we demonstrate that hcmv down-regulates hla-dr expression in infected interferon gamma (ifn-gamma)-stimulated fibroblasts at 1 day after infection. decreased hla-dr expression was not observed on cells infected with an hcmv strain lacking the pp65 gene (rvad65), but was observed on cells transfected with the pp65 gene. hla-dr expression accumulated in vacuoles near the nucleus in hcmv-infected, but ...200312609847
the human cytomegalovirus ul82 gene product (pp71) accelerates progression through the g1 phase of the cell cycle.as viruses are reliant upon their host cell to serve as proper environments for their replication, many have evolved mechanisms to alter intracellular conditions to suit their own needs. for example, human cytomegalovirus induces quiescent cells to enter the cell cycle and then arrests them in late g(1), before they enter the s phase, a cell cycle compartment that is presumably favorable for viral replication. here we show that the protein product of the human cytomegalovirus ul82 gene, pp71, ca ...200312610120
proteasome-dependent, ubiquitin-independent degradation of the rb family of tumor suppressors by the human cytomegalovirus pp71 protein.most of the substrates degraded by the proteasome are marked with polyubiquitin chains. however, there are a limited number of examples of nonubiquitinated proteins that are degraded by the proteasome. here, we describe the degradation of the retinoblastoma family of tumor suppressor proteins by the proteasome in the absence of polyubiquitination. the retinoblastoma protein (p105), p107, and p130 are each targeted for degradation by the pp71 protein, which is encoded by the ul82 gene of human cy ...200312626766
use of transgenic hla a*0201/kb and hhd ii mice to evaluate frequency of cytomegalovirus ie1-derived peptide usage in eliciting human cd8 cytokine response.unlike the pp65 protein of human cytomegalovirus (cmv), which has an immunodominant peptide, pp65(495-503), recognized by human cd8(+) cells in the context of hla a*0201, the fine peptide specificity for cmv ie1 has shown no such immunodominance. with the use of transgenic hla a*0201/kb and hhd ii mice, a selected pool of ie1 peptides, including ie1(p256-264), ie1(p297-304), and ie1(p316-324), were shown to stimulate cytolytic t-lymphocyte lysis in the context of hla a*0201. based on an intracel ...200312634406
relative dominance of hla-b*07 restricted cd8+ t-lymphocyte immune responses to human cytomegalovirus pp65 in persons sharing hla-a*02 and hla-b*07 alleles.cd8(+) t-cell responses to three human cytomegalovirus (cmv) pp65 epitopes were studied in panels of healthy seropositive hla-a*02/hla-b*07 individuals, and hla-a*02 donors mismatched for hla-b*07. the majority of the latter had significant responses to a hla-a*02-restricted epitope within the cmv pp65 antigen. by contrast, the strongest responses to cmv in the first group were to hla-b*07-restricted epitopes. similar immunodominance of hla-b*07 over hla-a*02 was found in two immunocompromised h ...200312651070
cytomegalovirus and epstein-barr virus dna transcription in endodontic symptomatic lesions.productive herpesviridae infections are implicated in the etio-pathogenesis of aggressive periodontitis. however, virtually nothing is known about a possible role of herpesviruses in pulpal and periapical pathosis. this study employed a cdna analysis to determine transcription of human cytomegalovirus (hcmv), epstein-barr virus (ebv) and herpes simplex virus (hsv) in 14 recalcitrant periapical lesions and in 2 periapical healthy control sites.200312654100
experimental study of mouse cytomegalovirus infected mice.in order to investigate the human cytomegalovirus (hcmv) infection, the mouse cytomegalovirus (mcmv) infected mice were experimentally studied. 6 to 8 week old female balb/c mice with immunosuppression were selected to undergo the mcmv inoculations: intracranial inoculation and peritoneal inoculation. mcmv of the infected mice in various organs and tissues were detected by using beta-gal staining and in situ nucleic acid hybridization assay. the pathological changes were observed in he staining ...200212658822
human cytomegalovirus infection in human renal arteries in vitro.studies with animal cytomegaloviruses, epidemiological data from humans as well as in vitro studies suggest the involvement of the human cytomegalovirus (hcmv) in the development of atherosclerosis. cell culture systems are insufficient for examination of the entire pathogenetic process and a satisfactory animal model for hcmv is not available. an organ culture model was established for hcmv infection of human renal arteries in vitro. after infection with three representative hcmv strains, infec ...200312668261
g-protein-coupled receptor (gpcr) kinase phosphorylation and beta-arrestin recruitment regulate the constitutive signaling activity of the human cytomegalovirus us28 gpcr.phosphorylation of g-protein-coupled receptors (gpcrs) by grks and subsequent recruitment of beta-arrestins to agonist-occupied receptors serves to terminate or attenuate signaling by blocking g-proteins from further interaction with the receptors. human cytomegalovirus encodes a gpcr termed us28 that is homologous to the human chemokine family of gpcrs but differs from the cellular receptors in that it maintains high constitutive activity in the absence of agonist. although us28 is constitutive ...200312668664
synthesis and antiviral activity of novel erythrofuranosyl imidazo[1,2-a]pyridine c-nucleosides constructed via palladium coupling of iodoimidazo[1,2-a]pyridines and dihydrofuran.2,5,6-trichloro-1-(beta-d-ribofuranosyl)benzimidazole (tcrb) and certain analogues have shown significant activity against human cytomegalovirus. the metabolic instability of the glycosidic linkage in tcrb prompted us to synthesize the structurally similar imidazo[1,2-a]pyridine erythrofuranosyl c-nucleosides. as an approach to the synthesis of polychlorinated imidazo[1,2-a]pyridine c-3-erythrofuranosides, a palladium-based methodology for coupling 2,3-dihydrofuran with chlorinated 3-iodoimidazo ...200312672244
mhc class i-like genes in cattle, mhcla, with similarity to genes encoding nk cell stimulatory ligands.a comparative genomics approach for mining databases of expressed sequence tags (ests) was used to identify two members of a novel mhc class i gene family in cattle. these paralogous genes, named mhc class i-like gene family a1 ( mhcla1) and mhcla2, were shown by phylogenetic analysis to be related to human and mouse genes encoding nk cell stimulatory ligands, ulbp, raet, h60 and raet-1. radiation hybrid mapping placed cattle mhcla1 on bta9, which, on the basis of existing comparative mapping da ...200312679856
intracellular retention of the mhc class i-related chain b ligand of nkg2d by the human cytomegalovirus ul16 glycoprotein.infection by human cmv induces expression of the cellular mhc class i-related chain a (mica) and chain b (micb) surface proteins, which function as ligands for the activating nkg2d receptor. engagement of nkg2d triggers nk cells and costimulates ag-specific effector cd8 alphabeta t cells. the potency of mhc class i-related chain-nkg2d in stimulating these anti-viral immune responses may be countered by a cmv-encoded transmembrane glycoprotein, ul16, which specifically binds micb as well as two o ...200312682252
ex vivo profiling of cd8+-t-cell responses to human cytomegalovirus reveals broad and multispecific reactivities in healthy virus carriers.human cytomegalovirus (hcmv) can establish both nonproductive (latent) and productive (lytic) infections. many of the proteins expressed during these phases of infection could be expected to be targets of the immune response; however, much of our understanding of the cd8(+)-t-cell response to hcmv is mainly based on the pp65 antigen. very little is known about t-cell control over other antigens expressed during the different stages of virus infection; this imbalance in our understanding undermin ...200312692225
endocytosis of the viral chemokine receptor us28 does not require beta-arrestins but is dependent on the clathrin-mediated pathway.arrestins bind phosphorylated g-protein coupled-receptors (gpcr) and inhibit agonist-induced signal transduction by uncoupling the receptors from their cognate g-proteins. beta-arrestins also act as adaptors that target gpcr to endocytic clathrin-coated vesicles. unlike cellular gpcrs, the human cytomegalovirus gpcrs and chemokine receptor, us28, shows constitutive signal transduction activity and undergoes constitutive endocytosis. to determine the role of beta-arrestins in us28 trafficking, we ...200312694563
expression of the ul16 glycoprotein of human cytomegalovirus protects the virus-infected cell from attack by natural killer cells.human cytomegalovirus (hcmv) has acquired through evolution a number of genes to try to evade immune recognition of the virus-infected cell. many of these mechanisms act to inhibit the mhc class i antigen presentation pathway, but any virus-infected cell which has down-regulated cell surface expression of mhc class i proteins, to avoid ctl attack, would be expected to become susceptible to lysis by natural killer cells. surprisingly, however, hcmv infected fibroblasts were found to be resistant ...200312694635
differential expression of chemokines by human retinal pigment epithelial cells infected with cytomegalovirus.to evaluate the effects of human cytomegalovirus (hcmv) infection on chemokine gene expression and secretion by human retinal pigment epithelial (hrpe) cell cultures.200312714640
herpesviral-bacterial interactions in aggressive periodontitis.human cytomegalovirus, epstein-barr virus and herpesvirus co-infections occur with significantly higher frequency in actively progressing than in stable periodontitis sites of adolescents and young adults. also, periodontal presence of cytomegalovirus and epstein-barr virus is associated with increased occurrence of subgingival porphyromonas gingivalis, bacteroides forsythus, dialister pneumosintes, prevotella intermedia, prevotella nigrescens, treponema denticola and actinobacillus actinomycete ...200312716334
role of murine cytomegalovirus us22 gene family members in replication in macrophages.the large cytomegalovirus (cmv) us22 gene family, found in all betaherpesviruses, comprises 12 members in both human cytomegalovirus (hcmv) and murine cytomegalovirus (mcmv). conserved sequence motifs suggested a common ancestry and related functions for these gene products. two members of this family, m140 and m141, were recently shown to affect mcmv replication on macrophages. to test the role of all us22 members in cell tropism, we analyzed the growth properties in different cell types of mcm ...200312719548
expression of an rnase p ribozyme against the mrna encoding human cytomegalovirus protease inhibits viral capsid protein processing and growth.a sequence-specific ribozyme (m1gs rna) derived from the catalytic rna subunit of rnase p from escherichia coli was used to target the mrna encoding human cytomegalovirus (hcmv) protease (pr), a viral protein that is responsible for the processing of the viral capsid assembly protein. we showed that the constructed ribozyme cleaved the pr mrna sequence efficiently in vitro. moreover, a reduction of about 80% in the expression level of the protease and a reduction of about 100-fold in hcmv growth ...200312729746
optimization of dna-based vaccination in cows using green fluorescent protein and protein a as a prelude to immunization against staphylococcal mastitis.staphylococcus aureus is a contagious pathogen that often results in chronic intramammary infections in dairy cows. current vaccine formulations are ineffective in preventing this infection. the objective of this study was to stimulate an immune response in dairy cows through injection of plasmid dna designed to express staphylococcal protein a in transfected cells. intramuscular and intradermal vaccination sites were evaluated using a plasmid containing the human cytomegalovirus (cmv) promoter/ ...200312741542
synergy of bovine lactoferrin with the anti-cytomegalovirus drug cidofovir in vitro.human cytomegalovirus (hcmv) causes severe morbidity and mortality in immunocompromised patients. treatment of hcmv infections with conventional antiviral drugs like ganciclovir and cidofovir has major drawbacks (i.e. serious side effects). therefore, combination therapies using drugs with different antiviral mechanisms should be envisaged. potential synergy between lactoferrin (lf), an antibacterial, antimycotic and antiviral protein, and the antiviral drugs acyclovir, ganciclovir, foscarnet an ...200312742576
[virus infection in children after allogenic stem cell transplantation ].allogenic hematopoietic cell transplantation (allohct) is the treatment of choice for various pediatric malignancies and nonmalignant diseases. the most prominent complication of allotransplantation is graft vs host disease (gvhd). the treatment of gvhd influence negatively function of immune system and increase risk of bacterial, fungal and viral infections. clinical symptoms of viral infection may mimic gvhd and lead to inappropriate treatment. human cytomegalovirus (cmv, herpesviridae) has be ...200312765120
human cytomegalovirus infection inhibits tumor necrosis factor alpha (tnf-alpha) signaling by targeting the 55-kilodalton tnf-alpha receptor.infection with human cytomegalovirus (hcmv) results in complex interactions between viral and cellular factors which perturb many cellular functions. hcmv is known to target the cell cycle, cellular transcription, and immunoregulation, and it is believed that this optimizes the cellular environment for viral dna replication during productive infection or during carriage in the latently infected host. here, we show that hcmv infection also prevents external signaling to the cell by disrupting the ...200312768019
antibacterial and antiviral effects of milk proteins and derivatives thereof.milk forms a rich source of biologically interesting components. in particular, its protein fraction is known to encompass many kinds of biological functions. in this review we focus on antibacterial and antiviral properties of milk proteins and milk protein derivatives. the latter include chemically modified proteins and enzymatically induced peptides. if such peptides are released by enzymes present within the digestive tract (e.g. trypsin or pepsin), it is likely that they play a role in the ...200312769735
the human cytomegalovirus.human cytomegalovirus (hcmv), a betaherpesvirus, represents the major infectious cause of birth defects, as well as an important pathogen for immunocompromised individuals. the viral nucleocapsid containing a linear double-stranded dna of 230 kb is surrounded by a proteinaceous tegument, which is itself enclosed by a loosely applied lipid bilayer. expression of the hcmv genome is controlled by a cascade of transcriptional events that leads to the synthesis of three categories of viral proteins d ...200312782241
mature cd8(+) t lymphocyte response to viral infection during fetal life.immunization of newborns against viral infections may be hampered by ineffective cd8(+) t cell responses. to characterize the function of cd8(+) t lymphocytes in early life, we studied newborns with congenital human cytomegalovirus (hcmv) infection. we demonstrate that hcmv infection in utero leads to the expansion and the differentiation of mature hcmv-specific cd8(+) t cells, which have similar characteristics to those detected in adults. high frequencies of hcmv-specific cd8(+) t cells were d ...200312782677
human cytomegalovirus glycoprotein ul16 causes intracellular sequestration of nkg2d ligands, protecting against natural killer cell cytotoxicity.the activating receptor, nkg2d, is expressed on a variety of immune effector cells and recognizes divergent families of major histocompatibility complex (mhc) class i-related ligands, including the mic and ulbp proteins. infection, stress, or transformation can induce nkg2d ligand expression, resulting in effector cell activation and killing of the ligand-expressing target cell. the human cytomegalovirus (hcmv) membrane glycoprotein, ul16, binds to three of the five known ligands for human nkg2d ...200312782710
elevated nitric oxide level in aqueous humor of aids patients with cytomegalovirus retinitis.human cytomegalovirus (hcmv) retinitis is the most common ocular opportunistic infection in aids. it often leads to blindness if left untreated. the questions as to how hcmv infection causes retinal immunopathogenesis and visual destruction in aids patients have not been completely established. here we reported that the nitric oxide (no) levels in aqueous humor samples in 10 aids patients with cmv retinitis (104.3 +/- 27.1 microm) were higher than the levels in 7 aids patients without cmv retini ...200312792138
dendritic cells and hcmv cross-presentation.the outcome of a viral infection is the result of an endless fight between the organism whose task is to mount an antiviral response and the virus that adapts strategies to circumvent the host response. human cytomegalovirus (hcmv), a latent herpesvirus, can be considered as a spearhead in exploiting co-existence with the host to develop numerous immuno-evasion mechanisms. the ability of the organism to initiate a primary immune response against viruses such as hcmv is highly dependent on the ca ...200312797453
non-hiv antivirals - a review of the recent patent literature.this review covers the non-hiv antiviral patent literature from december 2001 to april 2002. most of the patent applications describe new compounds for the treatment of hepatitis c virus (hcv) by inhibition of the ns3 serine protease. several examples of both nucleoside and non-nucleoside inhibitors of the hcv polymerase ns5b have been reported. hepatitis b virus (hbv) therapy continues to be dominated by nucleoside analogs, but several non-nucleoside hbv polymerase inhibitors have also been rep ...200212802698
neutralizing antibody to gb2 human cytomegalovirus does not prevent reactivation in patients with human immunodeficiency virus infection.the incidence of human cytomegalovirus (cmv) genotype gb2 (ul55) is high in patients with human immunodeficiency virus (hiv) infection in the san francisco bay area of california. virus neutralizing antibody (nab) to human cmv strain ad169, a gb2 laboratory strain, was measured prospectively in hiv-infected patients, with cd4 t-lymphocyte counts <200, who were at risk for cmv-associated disease. patients were grouped according to cmv dna copy number, as quantified by pcr, and presence or absence ...200312810879
polyubiquitin serves as a recognition signal, rather than a ratcheting molecule, during retrotranslocation of proteins across the endoplasmic reticulum membrane.polyubiquitination is required for retrotranslocation of proteins from the endoplasmic reticulum back into the cytosol, where they are degraded by the proteasome. we have tested whether the release of a polypeptide chain into the cytosol is caused by a ratcheting mechanism in which the attachment of polyubiquitin prevents the chain from moving back into the endoplasmic reticulum. using a permeabilized cell system in which major histocompatibility complex class i heavy chains are retrotranslocate ...200312813030
supernatants from human cytomegalovirus (hcmv)-infected retinal glial cells increase transepithelial electrical resistance in a cell culture model: evidence of hcmv immune escape in the eye?the underlying mechanisms leading to persistence of human cytomegalovirus (hcmv) in the immune privileged retina are not fully understood. this in vitro study was done to evaluate the influence of hcmv-infected retinal glial cells on epithelial barrier functions. glial cells derived from human eyes were cultured and infected with the clinical hcmv isolate hi91. supernatants of mock (gs(mock)) and hi91 (gs(hi91)) -infected glial cells were collected at 72 h post inoculation and used for incubatio ...200412827513
the human cytomegalovirus ul44 protein is a substrate for the ul97 protein kinase.the human cytomegalovirus ul97 protein is an unusual protein kinase that is able to autophosphorylate and to phosphorylate certain exogenous substrates, including nucleoside analogs such as ganciclovir. however, no natural substrate of ul97 in infected cells has been identified. we report here that recombinant ul44 protein became radiolabeled when incubated with recombinant ul97 and [(32)p]atp and that both proteins could be coimmunoprecipitated by an antibody that recognizes either protein. sub ...200312829811
clinical usefulness of human cytomegalovirus antigenemia assay after kidney transplantation.human (h) cytomegalovirus (cmv) infections are a major cause of morbidity and mortality among kidney transplants. we performed a prospective study to evaluate the clinical usefulness of hcmv antigenemia assay for preemptive treatment after kidney transplantation.200312829929
ubiquitinylation of the cytosolic domain of a type i membrane protein is not required to initiate its dislocation from the endoplasmic reticulum.human cytomegalovirus us2 and us11 target newly synthesized class i major histocompatibility complex (mhc) heavy chains for rapid degradation by the proteasome through a process termed dislocation. the presence of us2 induces the formation of class i mhc heavy chain conjugates of increased molecular weight that are recognized by a conformation-specific monoclonal antibody, w6/32, suggesting that these class i mhc molecules retain their proper tertiary structure. these conjugates are properly fol ...200312832421
no difference in type 1 t-cell immune responses to human cytomegalovirus antigens between atopic children and nonatopic children. 200312847503
detection of human cytomegalovirus, human herpesvirus type 6 and human herpesvirus type 7 in urine specimens by multiplex pcr.to develop a sensitive multiplex pcr to detect hcmv, hhv6 and hhv7, to test this pcr on urine specimens sent to the virus diagnostic laboratory and on stored urine samples from hiv-positive patients and their hiv-negative partners and to compare the sensitivity of the multiplex pcr with the diagnostic laboratory's routine service for the detection of hcmv.200312850164
benzothiadiazine dioxide human cytomegalovirus inhibitors: synthesis and antiviral evaluation of main heterocycle modified derivatives.the benzothiadiazine dioxide derivatives are potent non-nucleoside human cytomegalovirus (hcmv) inhibitors. as part of our comprehensive structure-activity relationship (sar) study of these compounds, we have now proposed structural modifications on the heterocyclic moiety both on the number and the nature of the fused heterocycle and on the kind of heteroatoms present on it. synthesis of these new compounds (benzyl derivatives of thiadiazines, thienothiadiazines, benzothienothiadiazines and qui ...200312856922
high prevalence of human cytomegalovirus in prostatic intraepithelial neoplasia and prostatic carcinoma.recent epidemiological data indicate that a history of increased exposure to sexually transmitted diseases is associated with an increased risk of prostate cancer. human cytomegalovirus (hcmv) is a member of the herpesvirus family, is sexually transmitted in adults and can persistently infect prostatic epithelium in non-immunocompromised hosts. based on increased awareness of the oncogenic potential of this virus, we decided to reexplore the issue of whether hcmv might be involved in prostate ca ...200312913758
local character of readthrough activation in adenovirus type 5 early region 1 transcription control.wild-type early activity of the adenovirus 5 e1b gene promoter requires readthrough transcription originating from the adjacent upstream e1a gene. this unusual mode of viral transcription activation was identified by genetic manipulation of the mouse beta(maj)-globin gene transcription termination sequence (ggt) inserted into the e1a gene. to facilitate further study of the mechanism of readthrough activation, the activities of ggt and a composite termination sequence ct were tested in recombina ...200312915542
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