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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 inhibits maturation and impairs function of monocyte-derived dendritic cells.dendritic cells (dcs) play a pivotal role in the generation of virus-specific cytotoxic t-cell responses, but some viruses can render dcs inefficient in stimulating t cells. we studied whether infection of dcs with human cytomegalovirus (hcmv) results in a suppression of dc function which may assist hcmv in establishing persistence. the effect of hcmv infection on the phenotype and function of monocyte-derived dcs and on their ability to mature following infection with an endothelial cell-adapte ...200211929782
lack of tumorigenesis in the mouse liver after adenovirus-mediated expression of a dominant stable mutant of beta-catenin.mutations in the glycogen synthase kinase 3beta (gsk3beta) phosphorylation sites of the beta-catenin gene exon 3 are found in 20-30% of human primary hepatocellular carcinoma (hcc), whereas mutations in the apc or axin genes are found in other hcc populations. these data strongly suggest that the wnt signaling pathway is involved in hepatocarcinogenesis. to determine the role of beta-catenin in intestinal tumorigenesis, we earlier constructed a mutant mouse strain catnb(lox(ex3)), in which exon ...200211929813
absence of ie1 p72 protein function during low-multiplicity infection by human cytomegalovirus results in a broad block to viral delayed-early gene expression.human cytomegalovirus (hcmv) ie1 deletion mutant cr208 is profoundly growth deficient after low-multiplicity infection of primary fibroblasts. previously, we showed that many fewer cells infected with cr208 at low multiplicity accumulated the delayed-early (de) protein ppul44 than accumulated the immediate-early 2 (ie2) p86 protein, indicating a high frequency of abortive infections. we now demonstrate that accumulation of all de proteins tested was defective after low-multiplicity infection in ...200211932411
[congenital human cytomegalovirus infection: value of human cytomegalovirus dna quantification in amniotic fluid].a quantitative pcr assay (rs elosa cmv, lambdatech) was used to quantitate hcmv dna in maternal amniotic fluid of 12 fetuses with congenital infection (group 1) and of 10 fetuses without congenital infection (group 2). hcmv detection was performed for both groups using culture and qualitative pcr. histologic examinations of fetal tissues and placenta were carried out for 9 patients from group 1. the amniotic fluid viral loads were negative in all patients of group 2. in group 1, all viral loads ...200211937445
emergence of multiple drug-resistant human cytomegalovirus variants in 2 patients with human immunodeficiency virus infection unresponsive to highly active antiretroviral therapy.in 2 patients infected with human immunodeficiency virus (hiv), highly active antiretroviral therapy was unable to suppress hiv replication as a result of the emergence of drug-resistant hiv variants. human cytomegalovirus (hcmv) retinitis developed in both patients, and an unusually complex mixture of drug-resistant hcmv variants was detected in both patients.200211915006
opinion article: cytomegalovirus is a risk factor in atherogenesis.whether or not infectious agents are involved in the pathogenesis of atherosclerosis has been a matter of discussion for the past 2 decades. although there is no definite proof of a causal role of human cytomegalovirus in atherogenesis, a body of knowledge supports the concept that this virus is involved in the development of atherosclerotic lesions. this review assesses the most important data published in support of this hypothesis.200211916496
dendritic cells cross-presenting viral antigens derived from autologous cells as a sensitive tool for visualization of human cytomegalovirus-reactive cd8+ t cells.cd8+ t lymphocytes are essential to contain viral infections, such as human cytomegalovirus (hcmv). to visualize these clinically important effector cells, we used dendritic cells (dc), which efficiently present exogenous antigens by mhc class i molecules (cross-presentation).200211923708
protective immunity against lethal hsv-1 challenge in mice by nucleic acid-based immunisation with herpes simplex virus type-1 genes specifying glycoproteins gb and gd.dna-based vaccines were employed to assess protective immunity against herpes simplex virus in experimental infections of hairless (strain skh1) and balb/c mice. mice were vaccinated with plasmids containing the herpes simplex virus type-1 (hsv-1) glycoprotein b (gb) or d (gd) genes under the human cytomegalovirus immediate-early promoter control. vaccines were injected intramuscularly (i.m.) or intraperitoneally (i.p.) as purified dna alone or as formulations supplemented with different non-ion ...200211926742
[tetrameric mhc-peptide complex identifying cd8+ t cells specific to epstein-barr virus and human cytomegalovirus]. 200211963184
endoplasmic reticulum stress-induced cell death requires mitochondrial membrane permeabilization. 200211965500
human cytomegalovirus gene products us2 and us11 differ in their ability to attack major histocompatibility class i heavy chains in dendritic cells.human cytomegalovirus (hcmv) encodes several proteins that inhibit major histocompatibility complex (mhc) class i-dependent antigen presentation. the hcmv products us2 and us11 are each sufficient for causing the dislocation of human and murine mhc class i heavy chains from the lumen of the endoplasmic reticulum to the cytosol, where the heavy chains are readily degraded. the apparent redundancy of us2 and us11 has been probed predominantly in cultured cell lines, where differences in their spec ...200211967320
retrieval of human cytomegalovirus glycoprotein b from cell surface is not required for virus envelopment in astrocytoma cells.human cytomegalovirus (hcmv) is a prototypic member of the betaherpesvirus family. the hcmv virion is composed of a large dna genome encapsidated within a nucleocapsid, which is wrapped within an inner proteinaceous tegument and an outer lipid envelope containing viral glycoproteins. although genome encapsidation clearly occurs in the nucleus, the subsequent steps in the virion assembly process are unclear. hcmv glycoprotein b (gb) is a major component of the virion envelope that plays a critica ...200211967330
antiviral activity of artesunate towards wild-type, recombinant, and ganciclovir-resistant human cytomegaloviruses.antiviral therapy of primary and recurrent infections with human cytomegalovirus is reserved for severe manifestations and faces several limitations. presently candidates for novel drugs with lower adverse side effects and a minimized frequency of resistance formation are under investigation. here we demonstrate that artesunate, an antimalaria drug with highly valuable pharmacological properties, possesses antiviral activity. a concentration-dependent inhibition of the replication of human cytom ...200211976732
real-time pcr quantification of human cytomegalovirus dna in amniotic fluid samples from mothers with primary infection.a real-time pcr assay was developed to quantify human cytomegalovirus (hcmv) dna in amniotic fluid (af) samples collected from 30 pregnant women with primary hcmv infection as detected either from hcmv-immunoglobulin g (igg) seroconversion or by the presence of hcmv-specific igg and igm associated with a low igg avidity. clinical information available for each case included ultrasonographic examination and fetal or newborn outcome. hcmv infection of fetuses or newborns was confirmed for the 30 s ...200211980958
sensitive detection of human cytomegalovirus peptide-specific cytotoxic t-lymphocyte responses by interferon-gamma-enzyme-linked immunospot assay and flow cytometry in healthy individuals and in patients after allogeneic stem cell transplantation.reconstitution of human cytomegalovirus (hcmv)-specific cytotoxic t lymphocytes (ctls), predominantly directed against pp65, provides protective immunity for the development of hcmv disease after allogeneic stem cell transplantation (sct). to define pp65-derived ctl epitopes that would allow sensitive detection of hcmv-specific immune reconstitution, a computer-based epitope prediction was performed. peptide-specific ctl responses were assessed by interferon-gamma release. with this approach, pp ...200211986243
human cytomegalovirus us7, us8, us9, and us10 are cytoplasmic glycoproteins, not found at cell surfaces, and us9 does not mediate cell-to-cell spread.human cytomegalovirus (hcmv) expresses a large number of membrane proteins with unknown functions. one class of these membrane proteins apparently acts to allow hcmv to escape detection by the immune system. the best characterized of these are the glycoproteins encoded within the us2 to us11 region of the hcmv genome that mediate resistance to cd8(+) and cd4(+) t cells. us2, us3, us6, and us11 block various aspects of the major histocompatibility complex (mhc) class i and class ii antigen presen ...200211992003
functional interaction between the pp71 protein of human cytomegalovirus and the pml-interacting protein human daxx.the tegument protein pp71 (ul82) of human cytomegalovirus (hcmv) has previously been shown to transactivate the major immediate-early enhancer-promoter of hcmv. furthermore, this protein is able to enhance the infectivity of viral dna and to accelerate the infection cycle, suggesting an important regulatory function during viral replication. to gain insight into the underlying mechanisms that are used by pp71 to exert these pleiotropic effects, we sought for cellular factors interacting with pp7 ...200211992005
quantitation of the spliced late gene of human cytomegalovirus and its kinetics during experimental infection.human cytomegalovirus (hcmv) infection is still a cause of morbidity and mortality after solid organ and bone marrow transplantation and in other immunocompromised states. 'preemptive therapy' strategies necessitate sensitive and specific methods for rapid diagnosis of symptomatic hcmv infection and monitoring of antiviral treatment. for analysis of the lytic stage of viral replication, the molecular determination of late transcripts is a useful approach for diagnosis of hcmv disease. in the pre ...200212005328
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
development and evaluation of an internally controlled semiautomated pcr assay for quantification of cell-free cytomegalovirus.quantification of circulating human cytomegalovirus (hcmv) is useful in clinical contexts such as virological surveillance of bone marrow transplant recipients and monitoring of antiviral therapy. this report describes an internally controlled, quantitative, semiautomated, hcmv genome assay that was developed primarily to measure hcmv dna in the plasma of severely leucopaenic patients. it exhibits greater sensitivity, wider dynamic range and higher sample throughput than a number of previously d ...200211857531
distinct glycoprotein o complexes arise in a post-golgi compartment of cytomegalovirus-infected cells.human cytomegalovirus (cmv) glycoproteins h, l, and o (gh, gl, and go, respectively) form a heterotrimeric disulfide-bonded complex that participates in the fusion of the viral envelope with the host cell membrane. during virus maturation, this complex undergoes a series of intracellular assembly and processing events which are not entirely defined (m. t. huber and t. compton, j. virol. 73:3886-3892, 1999). here, we demonstrate that go does not undergo the same posttranslational processing in tr ...200211861856
sumo-1 modification of human cytomegalovirus ie1/ie72.human cytomegalovirus (hcmv) immediate-early protein ie1/ie72 is involved in undermining many cellular processes including cell cycle regulation, apoptosis, nuclear architecture, and gene expression. the multifunctional nature of ie72 suggests that posttranslational modifications may modulate its activities. ie72 is a phosphoprotein and has intrinsic kinase activity (s. pajovic, e. l. wong, a. r. black, and j. c. azizkhan, mol. cell. biol. 17:6459-6464, 1997). we now demonstrate that ie72 is cov ...200211861864
human cytomegalovirus enhances chemokine production by lipopolysaccharide-stimulated lamina propria macrophages.to elucidate the role of mucosal macrophages in intestinal human cytomegalovirus (hcmv) disease, primary lamina propria macrophages (lpm) were isolated from normal human jejunum, infected with hcmv, and studied for their cytokine responses. hcmv infection of lpm was confirmed by the presence of hcmv ie72 (ul123), pp65 (ul83), and glycoprotein b (ul55) proteins, which were detected by immunofluorescence, beginning at postinfection (pi) day 3, and were sustained through pi day 12 in 0.1%-0.5% of l ...200211865414
visualization of the er-to-cytosol dislocation reaction of a type i membrane protein.the human cytomegalovirus gene products us2 and us11 induce proteasomal degradation of mhc class i heavy chains. we have generated an enhanced green fluorescent protein-class i heavy chain (egfp-hc) chimeric molecule to study its dislocation and degradation in us2- and us11-expressing cells. the egfp-hc fusion is stable in control cells, but is degraded rapidly in us2- or us11-expressing cells. proteasome inhibitors induce in a time-dependent manner the accumulation of egfp-hc molecules in us2- ...200211867532
construction of a rationally designed human cytomegalovirus variant encoding a temperature-sensitive immediate-early 2 protein.we generated a set of cysteine-to-glycine mutations and screened them to identify a temperature-sensitive allele of the human cytomegalovirus ul122 gene, which encodes the immediate-early 2 transcriptional activating protein. the mutant allele contains a single base pair substitution at amino acid 510. in transcription activation assays, the mutant protein activated the simian virus 40 early and human cytomegalovirus ul112 promoters at 32.5 degrees c but not at 39.5 degrees c. we constructed a m ...200211867756
us2, a human cytomegalovirus-encoded type i membrane protein, contains a non-cleavable amino-terminal signal peptide.the human cytomegalovirus us2 gene product targets major histocompatibility class i molecules for degradation in a proteasome-dependent fashion. degradation requires interaction between the endoplasmic reticulum (er) lumenal domains of us2 and class i. while er insertion of us2 is essential for us2 function, us2 lacks a cleavable signal peptide. radiosequence analysis of glycosylated us2 confirms the presence of the nh(2) terminus predicted on the basis of the amino acid sequence, with no eviden ...200211790769
terminally repeated sequences on a herpesvirus genome are deleted following circularization but are reconstituted by duplication during cleavage and packaging of concatemeric dna.the mechanisms underlying cleavage of herpesvirus genomes from replicative concatemers are unknown. evidence from herpes simplex virus type 1 suggests that cleavage occurs by a nonduplicative process; however, additional evidence suggests that terminal repeats may also be duplicated during the cleavage process. this issue has been difficult to resolve due to the variable numbers of reiterated terminal repeats that the herpes simplex virus type 1 genome can contain. guinea pig cytomegalovirus is ...200211799198
trail and its receptors in the colonic epithelium: a putative role in the defense of viral infections.tumor necrosis factor-related apoptosis-inducing ligand (trail) is a member of the tumor necrosis factor family and induces apoptosis by cross-linking either of the 2 trail receptors containing a death domain (trail-r1 or trail-r2). trail-r3 and trail-r4 are receptors that do not transmit an apoptotic signal. the aim of this study was to investigate the expression and function of trail and its receptors in normal colonic epithelium.200211874999
immune reactivity of human sera to the glycoprotein b of human herpesvirus 7.the glycoprotein b (gb) is highly conserved among distinct human herpesvirus 7 (hhv-7) strains. similarly to other herpesvirus glycoproteins, gb has been assumed to induce a specific human immune response. however, it did not appear as an immunodominant protein in conventional immunoblot assays. recombinant gb, obtained from either escherichia coli or baculovirus expression systems, did react specifically with hhv-7-seropositive sera, and the main corresponding epitopes were located in its n-ter ...200211773091
identification of glycoprotein gptrl10 as a structural component of human cytomegalovirus.human cytomegalovirus (hcmv) has a coding capacity for glycoproteins which far exceeds that of other herpesviruses. few of these proteins have been characterized. we have investigated the gene product(s) of reading frame 10, which is present in both the internal and terminal repeat regions of hcmv strain ad169 and only once in clinical isolates. the putative protein product is a 171-amino-acid glycoprotein with a theoretical mass of 20.5 kda. we characterized the protein encoded by this reading ...200211773418
u(s)3 protein kinase of herpes simplex virus 1 blocks caspase 3 activation induced by the products of u(s)1.5 and u(l)13 genes and modulates expression of transduced u(s)1.5 open reading frame in a cell type-specific manner.the coding domain of the herpes simplex virus type 1 (hsv-1) alpha22 gene encodes two proteins, the 420-amino-acid infected-cell protein 22 (icp22) and u(s)1.5, a protein colinear with the carboxyl-terminal domain of icp22. in hsv-1-infected cells, icp22 and u(s)1.5 are extensively modified by the u(l)13 and u(s)3 viral protein kinases. in this report, we show that in contrast to other viral proteins defined by their properties as alpha proteins, u(s)1.5 becomes detectable and accumulated only a ...200211752164
characterization of a human cytomegalovirus with phosphorylation site mutations in the immediate-early 2 protein.a human cytomegalovirus mutant (tnsubie2p) was constructed with alanine substitutions of four residues (t27, s144, t233, and s234) previously shown to be phosphorylated in the immediate-early 2 (ie2) protein. this mutant grew as well as the wild type at both low and high multiplicities of infection. the mutant activated the major immediate-early, ul4, and ul44 promoters to similar levels, and with similar kinetics, as wild-type virus. however, the tnsubie2p mutant virus transactivated an endogen ...200211752183
the human elongation factor 1 alpha (ef-1 alpha) first intron highly enhances expression of foreign genes from the murine cytomegalovirus promoter.in order to develop a highly efficient mammalian expression vector, we constructed a vector by the combination of the murine cytomegalovirus (mcmv) immediate early (ie) promoter and the human elongation factor one alpha (ef-1 alpha) first intron. the mcmv ie promoter was several fold stronger than the human cytomegalovirus (hcmv) immediate early (ie) promoter and the human elongation factor one alpha (ef-1 alpha) promoter in various mammalian cell lines such as nih3t3, neuro-2a, 293t or ht1080 a ...200211738725
novel baculovirus dna elements strongly stimulate activities of exogenous and endogenous promoters.a dna sequence upstream from the polyhedrin gene of baculovirus autographa californica nucleopolyhedrovirus (acmnpv) was found to activate strongly the expression of full or minimal promoters derived from acmnpv and other sources. promoters tested included the minimal cmv (cmvm) promoter from human cytomegalovirus, the full heat shock 70 promoter from drosophila, and the minimal p35 promoter from baculovirus. deletion and mutagenesis analyses showed that this functional polyhedrin upstream (pu) ...200211741907
multiplex real-time nasba for monitoring expression dynamics of human cytomegalovirus encoded ie1 and pp67 rna.the monitoring for hcmv mrna expression in whole blood provides an accurate and informative diagnostic approach.200211744429
atpase activity of the terminase subunit pul56 of human cytomegalovirus.herpesviral dna packaging is a complex process resulting in unit-length genomes packed into preformed procapsids. this process is believed to be mediated by two packaging proteins, the terminase subunits. in the case of double-stranded dna bacteriophages, the translocation of dna was shown to be an energy-dependent process associated with an atpase activity of the large terminase subunit. in the case of human cytomegalovirus it was not known which protein has the ability to hydrolyze atp. in thi ...200211744697
gcv resistance due to the mutation a594p in the cytomegalovirus protein ul97 is partially reconstituted by a second mutation at d605e.a ganciclovir (gcv)-resistant human cytomegalovirus (hcmv) was isolated from an aids patient. molecular analysis of the hcmv ul97 gene revealed two point mutations, a594p and d605e, respectively. in order to evaluate quantitatively the impact of the individual mutations on gcv phosphorylation, recombinant vaccinia viruses (rvvs) were generated carrying either the two mutations (rvv-594/605) or only one mutation (rvv-594 or rvv-605, respectively). in cells infected with the rvv-594/605 double mut ...200211750939
membrane-specific, host-derived factors are required for us2- and us11-mediated degradation of major histocompatibility complex class i molecules.human cytomegalovirus encodes two glycoproteins, us2 and us11, that target major histocompatibility complex (mhc) class i heavy chains for proteasomal degradation. we have developed a mrna-dependent cell-free system that recapitulates us2- and us11-mediated degradation of mhc class i heavy chains. microsomes support the degradation of mhc class i heavy chains in the presence of us2 or us11 in a cytosol-dependent manner. in vitro, the glycosylated heavy chain is exported from the microsomes. a de ...200211717308
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 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
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
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
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
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
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