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kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) contains hypoxia response elements: relevance to lytic induction by hypoxia.kaposi's sarcoma (ks)-associated herpesvirus (kshv), also known as human herpesvirus 8, is an etiologic agent of ks, primary effusion lymphoma (pel), and multicentric castleman's disease. we recently demonstrated that hypoxia can induce lytic replication of kshv in pel cell lines. hypoxia induces the accumulation of hypoxia-inducible factors (hif), and we hypothesized that the kshv genome may respond to hypoxia through functional hypoxia response elements (hres). here, we demonstrate the presenc ...200312767996
the latency protein lana2 from kaposi's sarcoma-associated herpesvirus inhibits apoptosis induced by dsrna-activated protein kinase but not rnase l activation.kaposi's sarcoma-associated herpesvirus (kshv) uses several strategies to counteract the interferon (ifn) system. in this study, the relationship of the protein lana2 from kshv to the ifn-activated protein kinase (pkr) and 2-5a system was analysed. it was found that lana2 could not abrogate apoptosis or rna degradation mediated by the 2-5a system. however, expression of lana2 inhibited apoptosis triggered by pkr. lana2 also counteracted the pkr-mediated inhibition of protein synthesis and partia ...200312771415
glycoproteins m and n of human herpesvirus 8 form a complex and inhibit cell fusion.glycoproteins m (gm) and n (gn) are well conserved across the herpesvirus family and their involvement in virus penetration and egress is well described, especially for alphaherpesviruses. because there was no previous study on the homologues of human herpesvirus 8 glycoproteins m (gm8) and n (gn8), we analysed their biochemical and functional characteristics. we found that: (i) gm8 aggregated following heat treatment; (ii) gm8 was a virion component; (iii) gm8 and gn8 were n-glycosylated; (iv) ...200312771417
classic kaposi's sarcoma of the palm in a metallurgist: role of iron filings in its development? 200312786847
lytic switch protein (orf50) response element in the kaposi's sarcoma-associated herpesvirus k8 promoter is located within but does not require a palindromic structure.kaposi's sarcoma-associated virus (kshv) orf50 protein induces lytic replication and activates the k8 promoter. we show that orf50-induced and tetradecanoyl phorbol acetate (tpa) induced k8 transcripts initiated from the same start site. a newly identified palindrome (pal2), containing a 12-bp response region required for orf50-induced activation in lymphoid cells, was identified in the k8 promoter. specific dna binding of bacterially expressed orf50 was not seen with the k8 promoter despite spe ...200312788632
seropositivity of human herpesvirus-8 in patients with uveitis.to explore the role of human herpesvirus-8 (hhv-8) in the pathogenesis of uveitis and other forms of ocular inflammation.200212789595
molecular analysis of human herpesvirus 8 by using single nucleotide polymorphisms in open reading frame 26.human herpesvirus 8 (hhv-8) can be classified into distinct subtypes on the basis of sequence polymorphisms in several open reading frames (orfs). we analyzed the subtypes of hhv-8 in 59 human immunodeficiency virus-infected japanese patients by using polymorphisms in orf26 and found that over two-thirds of the hhv-8 isolates fell into major subtype a. we also found that single nucleotide polymorphisms (snps) at nucleotide positions 1032 (c-to-a substitution) and 1055 (g-to-t substitution) in hh ...200312791871
evidence for a recessive major gene predisposing to human herpesvirus 8 (hhv-8) infection in a population in which hhv-8 is endemic.infection by human herpesvirus 8 (hhv-8), as measured by the presence of specific antibodies, was shown in countries in which hhv-8 infection is endemic to exhibit familial aggregation and a peculiar variation with age (rapid increase until puberty followed by a plateau in young adults). to investigate whether host genetic factors could explain these findings, a segregation analysis was performed of 81 families of african origin (1623 subjects; hhv-8 seroprevalence, 11.9%) living in a village in ...200312792871
kaposi's sarcoma in a human immunodeficiency virus-negative patient treated with corticosteroid for idiopathic thrombocytopenic purpura. 200312793720
sustained high levels of serum hhv-8 dna years before multicentric castleman's disease despite full suppression of hiv with highly active antiretroviral therapy. 200312799569
selective gene expression of latent murine gammaherpesvirus 68 in b lymphocytes.intranasal infection of mice with murine gammaherpesvirus 68 (mhv-68), a virus genetically related to the human pathogen kaposi's sarcoma-associated herpesvirus, results in a persistent, latent infection in the spleen and other lymphoid organs. here, we have determined the frequency of virus infection in splenic dendritic cells, macrophages, and several b-cell subpopulations, and we quantified cell type-dependent virus transcription patterns. the frequencies of virus genome positive cells were m ...200312805429
establishment and maintenance of gammaherpesvirus latency are independent of infective dose and route of infection.gammaherpesviruses such as epstein-barr virus and kaposi's sarcoma-associated herpesvirus are important human pathogens that establish long-term latent infections. understanding of the initiation and maintenance of latent infections has important implications for the prevention and treatment of gammaherpesvirus-related diseases. although much is known about gammaherpesvirus pathogenesis, it is unclear how the infectious dose of a virus influences its ability to establish latent infection. to exa ...200312805472
virally encoded g protein-coupled receptors: targets for potentially innovative anti-viral drug development.various herpes- and poxviruses contain dna sequences encoding proteins with homology to cellular chemokine receptors, which belong to the family of g protein-coupled receptors (gpcrs). since gpcrs play a crucial role in cellular communication and chemokine receptors play a prominent role in the immune system, the virally encoded gpcrs may be crucial determinants of viral action. the kaposi's sarcoma-associated herpesvirus (kshv, or human herpesvirus 8), implicated in the pathogenesis of kaposi's ...200312816350
kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) infection of human fibroblast cells occurs through endocytosis.kaposi's sarcoma (ks)-associated herpesvirus or human herpesvirus 8 (hhv-8) dna and transcripts have been detected in the b cells, macrophages, keratinocytes, and endothelial and epithelial cells of ks patients. in vitro, hhv-8 infects human b, endothelial, epithelial, and fibroblast cells, as well as animal cells, and the infection is characterized by (i) absence of lytic replication by the input virus and (ii) latent infection. for its initial binding to target cells, hhv-8 uses ubiquitous hep ...200312829837
structural analysis of the kaposi's sarcoma-associated herpesvirus k1 protein.the k1 protein of kaposi's sarcoma-associated herpesvirus (kshv) efficiently transduces extracellular signals to elicit cellular activation events through its cytoplasmic immunoreceptor tyrosine-based activation motif (itam). in addition, the extracellular domain of k1 demonstrates regional homology with the immunoglobulin (ig) family and contains conserved regions (c1 and c2) and variable regions (v1 and v2). to generate mouse monoclonal antibodies directed against the kshv k1 protein, balb/c m ...200312829846
rituximab therapy for hiv-associated castleman disease.to assess the clinical benefit of rituximab for hiv-associated castleman disease, 5 patients infected with hiv with histologic-proven castleman disease were prospectively enrolled to receive 4 infusions of rituximab. clinical and biologic parameters (c-reactive protein, cd19 cell count, kaposi sarcoma-associated herpesvirus [kshv] viral load in peripheral blood mononuclear cells) were assessed before and at different time points following rituximab infusions. two patients died very quickly after ...200312842986
viruses as potential targets for therapy in hiv-associated malignancies.epstein-barr virus or kaposi's sarcoma herpesvirus--and, at times, both viruses--are present in the tumor cells of many hiv-associated malignancies. their presence provides potential therapeutic targets for adoptive immunotherapy with antigen-specific t cells, vaccines to induce specific t-cell responses, and pharmacologic therapies to kill tumor cells or alter their malignant phenotype.200312852651
pathogenesis of kaposi's sarcoma.kaposi's sarcoma (ks) is a disease characterized by proliferative vascular lesions, which almost invariably contain the ks-associated herpesvirus (kshv), also called human herpesvirus 8. kshv is a lymphotrophic and angiotrophic herpesvirus, whose genome encodes several proteins involved in proliferation, antiapoptotic functions, and inflammation. most ks spindle cells express latent kshv genes, but a few express lytic genes, which might be involved in angiogenic and paracrine mechanisms that con ...200312852653
clinical presentations and standard therapy of aids-associated kaposi's sarcoma.the treatment plan for a patient with aids-related ks should be based on tumor characteristics, control of hiv infection, comorbidities, and patient treatment goals (see table 1). institution of optimal antiretroviral therapy is an essential component of ks therapy. when available, enrollment in a clinical trial should be considered, except for patients who are naive to chemotherapy with symptomatic or life-threatening ks. for a patient with minimal, indolent cutaneous disease, after optimal con ...200312852654
therapy of aids-associated kaposi's sarcoma: targeting pathogenetic mechanisms.only a small number of the many agents with the potential to inhibit factors known to stimulate ks growth have been tested clinically, and many were investigated at a time when treatment options for hiv infection were relatively ineffective. the failure of some of these agents to induce ks regression may not signify failure to achieve a relevant biologic effect in all cases, but may simply mean that in a neoplasm that expresses a broad array of growth factors, inhibition of a single factor may b ...200312852655
kaposi's sarcoma of the conjunctiva leads to a diagnosis of acquired immunodeficiency syndrome. 200312859274
aids-related kaposi's sarcoma: evaluation of potential new prognostic factors and assessment of the aids clinical trial group staging system in the haart era--the italian cooperative group on aids and tumors and the italian cohort of patients naive from antiretrovirals.to assess potential new prognostic factors and to validate the aids clinical trials group (actg) for aids-related kaposi's sarcoma (aids-ks) staging system in the highly active antiretroviral therapy (haart) era.200312885804
prevalence and indicators of hiv and aids among adults admitted to medical and surgical wards in blantyre, malawi.despite high seroprevalence there are few recent studies of the effect of human immunodeficiency virus (hiv) on hospitals in sub-saharan africa. we examined 1226 consecutive patients admitted to medical and surgical wards in blantyre, malawi during two 2-week periods in october 1999 and january 2000: 70% of medical patients were hiv-positive and 45% had acquired immune deficiency syndrome (aids); 36% of surgical patients were hiv-positive and 8% had aids. seroprevalence rose to a peak among 30-4 ...200312886812
kshv vflip binds to ikk-gamma to activate ikk.when expressed in heterologous cells, the viral flip protein (vflip) of kaposi's-sarcoma-associated herpesvirus (kshv) has been reported both to block fas-mediated apoptosis and to activate the nf-kappab activation pathway by interaction with ikappab kinase (ikk). in a yeast-two-hybrid screen, we identified ikkgamma as an interacting partner of vflip. we expressed fragments of ikkgamma in mammalian cells and bacteria, and identified the central ccr3/4 (amino acids 150-272) as the vflip binding r ...200312890756
kshv reactivation in post-transplant kaposi sarcoma. 200312894151
human herpesvirus 8-associated diseases in solid-organ transplantation: importance of viral transmission from the donor. 200312905148
the role of kaposi's sarcoma-associated herpesvirus/human herpesvirus-8 regulator of transcription activation (rta) in control of gene expression.the mechanisms that control the replication state, latency versus lytic, of human herpesviruses have been under intense investigations. here we summarize some of the recent findings that help define such mechanisms for kaposi's sarcoma-associated herpesvirus/human herpesvirus type 8 (kshv/hhv-8). for hhv-8, the viral regulator of transcription activation (rta) is a key mediator of the switch from latency to lytic gene expression in infected cells. rta is necessary and sufficient to drive hhv-8 l ...200312910252
kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 transcriptional activator rta is an oligomeric dna-binding protein that interacts with tandem arrays of phased a/t-trinucleotide motifs.kaposi's sarcoma associated herpesvirus (kshv)/human herpesvirus 8 (hhv-8) encodes an immediate early transcriptional activator, rta, which mediates viral reactivation from latency and lytic viral replication. here we report the purification and characterizations of hhv-8 rta and its interaction with rta-responsive dna elements. the rta response element (rtare) in the promoter of the kshv/hhv-8 k8 open reading frame was mapped to a 47-bp sequence (rtare1) and a 60-bp sequence (rtare2) upstream o ...200312915555
ccaat/enhancer-binding protein-alpha is induced during the early stages of kaposi's sarcoma-associated herpesvirus (kshv) lytic cycle reactivation and together with the kshv replication and transcription activator (rta) cooperatively stimulates the viral rta, mta, and pan promoters.during the immediate-early (ie) phase of reactivation from latency, the kaposi's sarcoma-associated herpesvirus (kshv) replication and transcription activator protein (rta) (or orf50) is thought to be the most critical trigger that upregulates expression of many downstream viral lytic cycle genes, including the delayed-early (de) gene encoding the replication-associated protein (rap) (or k8). rap physically interacts with and stabilizes the cellular transcription factor ccaat/enhancer-binding pr ...200312915572
surface downregulation of major histocompatibility complex class i, pe-cam, and icam-1 following de novo infection of endothelial cells with kaposi's sarcoma-associated herpesvirus.under selective pressure from host cytotoxic t lymphocytes, many viruses have evolved to downregulate major histocompatibility complex (mhc) class i and/or t-cell costimulatory molecules from the surface of infected cells. kaposi's sarcoma-associated herpesvirus (kshv) encodes two proteins, mir-1 and mir-2, that serve this function during lytic replication. in vivo, however, kshv exists in a predominantly latent state, with less than 5% of infected cells expressing discernible lytic gene product ...200312915579
multicenter comparison of serologic assays and estimation of human herpesvirus 8 seroprevalence among us blood donors.as part of assessing the possibility of transfusion transmission of human herpesvirus 8 (hhv-8 or kaposi's sarcoma-associated herpesvirus), hhv-8 seroprevalence was estimated among us blood donors, the performance of hhv-8 serologic tests was compared, and the presence of hhv-8 dna was tested for in donated blood.200312919429
kaposi's sarcoma-associated herpesvirus-infected primary effusion lymphoma has a plasma cell gene expression profile.kaposi's sarcoma-associated herpesvirus is associated with three human tumors: kaposi's sarcoma, and the b cell lymphomas, plasmablastic lymphoma associated with multicentric castleman's disease, and primary effusion lymphoma (pel). epstein-barr virus, the closest human relative of kaposi's sarcoma-associated herpesvirus, mimics host b cell signaling pathways to direct b cell development toward a memory b cell phenotype. epstein-barr virus-associated b cell tumors are presumed to arise as a cons ...200312925741
seroprevalence of hhv 8 antibodies among the general population and hiv positive persons in the czech republic.the seroprevalence rates of herpesvirus 8 (hhv 8) antibodies were determined for the general czech population and hiv-positive individuals.200312927753
productive lytic replication of a recombinant kaposi's sarcoma-associated herpesvirus in efficient primary infection of primary human endothelial cells.kaposi's sarcoma-associated herpesvirus (kshv) is linked to the development of kaposi's sarcoma (ks), a vascular spindle cell tumor primarily consisting of proliferating endothelial cells. although kshv has been shown to infect primary human endothelial cells and convert them into spindle shapes, kshv infection is largely latent, and efforts to establish a highly efficient and sustainable infection system have been unsuccessful. a recombinant kshv, bac36, that has high primary-infection efficien ...200312941882
real-time pcr provides improved detection and titer determination of bacteriophage.the plaque assay is the traditional method for the quantification of bacteriophage, particularly for lambda cloning vectors. unfortunately, this technique is fraught with procedural difficulties, and the quality of the data obtained from this "gold standard" assay may be inaccurate due to the subjective interpretation of the results. the application of quantitative real-time pcr (qpcr) technology can address these issues and be a more accurate platform to evaluate phage growth conditions and qua ...200312951778
human herpesvirus 8 infection and transfusion history in children with sickle-cell disease in uganda.although human herpesvirus 8 (hhv-8), the etiologic agent for kaposi's sarcoma, can be detected in peripheral blood, blood-borne transmission of this virus has not been demonstrated. we studied the association between hhv-8 seropositivity and transfusion history among children with sickle-cell disease in uganda, where hhv-8 infection is common in blood donors.200312953087
hiv protease inhibitors as new treatment options for kaposi's sarcoma.a reduced incidence and regression of kaposi's sarcoma (ks) and other tumours has been reported in acquired immune deficiency syndrome (aids) patients treated with antiretroviral combination therapies containing human immunodeficiency virus (hiv) protease inhibitors (pis) such as indinavir or saquinavir. indeed, evidence indicates that although pis were designed to selectively inhibit the hiv protease activity, they can interfere with several cellular pathways and can inhibit tumour growth. in p ...200312962683
multicentric castleman's disease treated with antivirals and immunosuppressants.a patient negative for human immunodeficiency virus (hiv) developed multicentric castleman's disease (mcd) and kaposi's sarcoma (ks) associated with active human herpesvirus 8 (hhv-8) infection. he was treated with sequential antiviral therapy, chemotherapy, and corticosteroids. hhv-8 levels were monitored throughout the course of the patient's illness, and were found to rise on relapse. no consistent change in hhv-8 levels was found with antiviral therapy. we demonstrate that in this patient an ...200312966545
herpesvirus entry: an update. 200312970403
kaposi's sarcoma-associated herpesvirus--the high cost of viral survival. 200313679522
expression of human herpesvirus 8 in primary pulmonary hypertension.severe pulmonary hypertension constitutes a group of diseases characterized by complex, lumen-occluding vascular lesions that develop in genetically susceptible persons. the only viral infection associated with severe pulmonary hypertension has been that due to human immunodeficiency virus type 1, but neither the viral genome nor viral antigens have been demonstrated in pathologic lesions.200313679525
kaposi's sarcoma is not a neoplasm let alone a sarcoma. 200314521707
lytic replication of human herpesvirus 8 and induction of apoptosis.although many viruses can induce apoptosis in infected cells, large dna viruses, such as poxviruses, herpesviruses and adenoviruses, usually exhibit the ability to suppress the induction of apoptosis in the infected cells. we investigated the ability of human herpesvirus 8 (hhv-8) to protect cells from apoptosis induced by the virus. hhv-8 has been shown to harbor genes with anti-apoptotic capacity. however, we demonstrate here that a lytic replication of hhv-8 resulted in induction of apoptosis ...200314524475
immunohistochemical detection of the human herpes virus 8 (hhv8) latent nuclear antigen-1 in kaposi's sarcoma.the molecular genetics of the human herpes virus 8 (hhv8) has now been characterised and the virus appears to be important in the pathogenesis of kaposi's sarcoma (ks). this study attempts to determine the rate of hhv8 infection in ks in an australian cohort.200314555392
molecular epidemiology of kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 strains from russian patients with classic, posttransplant, and aids-associated kaposi's sarcoma.we report the molecular characterization of 38 new kaposi's sarcoma-associated herpesvirus (kshv) strains from russian patients with either classic (25 cases), epidemic/aids-associated (7 cases), or posttransplant/immunosuppressed patients (6 cases), or kaposi's sarcoma (ks). while a complete sequence of the k1 gene (870 bp) was obtained from 30 strains, only partial sequences of the hypervariable regions vr1 (372 bp) and/or vr2 (381 bp) of the k1 gene were obtained from eight strains of ks para ...200314556268
chromatin remodeling of the kaposi's sarcoma-associated herpesvirus orf50 promoter correlates with reactivation from latency.the switch from latent to lytic infection of kaposi's sarcoma-associated herpesvirus is initiated by the immediate early transcriptional activator protein rta/open reading frame 50 (orf50). we examined the transcriptional regulation of the orf50 core promoter in response to lytic cycle stimulation. we show that the orf50 promoter is highly responsive to sodium butyrate (nab) and trichostatin a (tsa), two chemicals known to inhibit histone deacetylases. the nab and tsa responsive element was mapp ...200314557628
epidermal growth factor receptor expression in follicular dendritic cells: a shared feature of follicular dendritic cell sarcoma and castleman's disease.the factors regulating the growth of follicular dendritic cell (fdc) sarcoma are currently unknown. using cdna microarray analysis, we found that the epidermal growth factor receptor (egfr) is expressed in fdc sarcoma. we immunohistochemically examined the expression of egfr in a larger series of fdc sarcomas and in nonneoplastic fdcs. this included 8 cases of fdc sarcoma, 12 cases of hyaline vascular castleman's disease (cd), 5 cases of human herpesvirus 8 (hhv8)-positive plasma cell cd, 7 case ...200314562277
[misleading kaposi's sarcoma: usefulness of anti hhv-8 immunostaining].we report two cases of early kaposi's sarcoma illustrating the risk of misdiagnosis. both lesions showed histological features and clinical aspects that mimicked lymphangioendothelioma. the diagnosis of lymphangioma-like kaposi's sarcoma was not made until a few years later, after the lesions had become more extensive and bilateral. because of this evolution which is uncommon for a lymphangioendothelioma, immunohistochemical staining with anti-hhv8 antibody was done, and was positive in successi ...200314597899
rna interference: a potential tool against kaposi's sarcoma-associated herpesvirus.rna interference is a conserved cellular function that controls viral infection, the expression of transposable elements, repetitive sequences and genes in embryonic development. originally described as an antiviral mechanism in plants, known as posttranscriptional gene silencing, it is now appreciated that this phenomenon occurs in all living cells. double-stranded rna, when acting as part of rna interference, reduces expression of genes with sequence similarity, but has no effect on the expres ...200314624111
de novo infection with rhesus monkey rhadinovirus leads to the accumulation of multiple intranuclear capsid species during lytic replication but favors the release of genome-containing virions.rhesus monkey rhadinovirus (rrv) is one of the closest phylogenetic relatives to the human pathogen kaposi's sarcoma-associated herpesvirus (kshv), yet it has the distinct experimental advantage of entering efficiently into lytic replication and growing to high titers in culture. rrv therefore holds promise as a potentially attractive model with which to study gammaherpesvirus structure and assembly. we have isolated rrv capsids, determined their molecular composition, and identified the genes e ...200314645602
generation and precise modification of a herpesvirus saimiri bacterial artificial chromosome demonstrates that the terminal repeats are required for both virus production and episomal persistence.herpesvirus saimiri (hvs) is the prototype gamma-2 herpesvirus, and shares considerable homology with the human gammaherpesviruses kaposi's sarcoma-associated herpesvirus and epstein-barr virus. the generation of herpesvirus mutants is a key facet in the study of virus biology. the use of f-factor-based bacterial artificial chromosomes (bacs) to clone and modify the genomes of herpesviruses has enhanced the variety, precision and simplicity of mutant production. here we describe the cloning of t ...200314645920
the kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 n terminus is essential for chromosome association, dna replication, and episome persistence.to persist in latently infected, proliferating cells, kaposi's sarcoma-associated herpesvirus (kshv) episomes must replicate and efficiently segregate to progeny nuclei. episome persistence in uninfected cells requires latency-associated nuclear antigen 1 (lana1) in trans and cis-acting kshv terminal repeat (tr) dna. the lana1 c terminus binds tr dna, and lana1 mediates tr-associated dna replication in transient assays. lana1 also concentrates at sites of kshv tr dna episomes along mitotic chrom ...200414671111
oral kaposi's sarcoma: a clinicopathologic study from south africa.in this retrospective study, we defined the clinicopathologic characteristics of oral kaposi's sarcoma (ks) and determined the presence of human herpesvirus 8 in the oral lesions in a group of south african patients. these results were compared with similar data from patients in developed countries.200314676761
changing paradigms in dermatology: antivirals in dermatology.almost all of the approved antiviral drugs have become available during the past two decades. approximately one half of these agents are for the treatment of human immunodeficiency virus (hiv) infections and comprise five classes. the first three classes all act to inhibit reverse transcriptase: nucleoside analogs; nonnucleoside analogs; and nucleotide analogs. the fourth class, protease inhibitors, prevent viral packaging; the fifth class, fusion inhibitors, prevent fusion between hiv and the t ...200314678723
activation of p21-activated kinase 1-nuclear factor kappab signaling by kaposi's sarcoma-associated herpes virus g protein-coupled receptor during cellular transformation.kaposi's sarcoma-associated herpes virus (kshv) contributes to the pathogenesis of kaposi's sarcoma and primary effusion lymphomas. kshv encodes a g protein-coupled receptor (kshv-gpcr) that signals constitutively and transforms nih3t3 cells. here, we show that kshv-gpcr transformation requires activation of the small g protein rac1 and its effector, the p21-activated kinase 1 (pak1). either transient or sustained expression of kshv-gpcr activated both rac1 and pak1. furthermore, expression of d ...200314695200
human herpesvirus 8 and epstein-barr virus-related monotypic large b-cell lymphoproliferative disorder coexisting with mixed variant of castleman's disease in a lymph node of a renal transplant recipient.human herpesvirus 8 (hhv8) has been related to some malignant lymphoproliferations, including post-transplant lymphoproliferative disorders (ptld). we describe a case of a hhv8 and epstein-barr virus (ebv) positive large b-cell lymphoproliferation coexisting with castleman's disease in the same lymph node of a long-term renal transplant recipient. biopsy revealed mixed type of castleman's disease and anaplastic cells showing iga restriction, although molecular analysis failed to detect monoclona ...200314703929
inflammatory fibroid polyps of the gastrointestinal tract: evidence for a dendritic cell origin.inflammatory fibroid polyps (ifps) are rare mesenchymal tumors of the gastrointestinal tract that consist of spindle-shaped stromal cells and an inflammatory infiltrate rich in eosinophils. their etiology and histogenesis remain unknown. based on previous reports of their immunoreactivity for cd34 and c-kit biomarkers, ifps have been thought to be related to gastrointestinal stromal tumors (gists). after reviewing the current literature and examining ifps at the light microscopic level, we evalu ...200414707872
species identification of all eight human herpesviruses with a single nested pcr assay.there are eight currently known human herpesviruses, all of which are capable of latent persistence and reactivation following primary infection. herpesvirus induced disease is common, widespread, and associated with significant morbidity, particularly in the immunocompromised human host. current methods of herpesvirus detection include viral culture and polymerase chain reaction (pcr). a robust pcr method based upon amplification of the highly conserved herpesvirus dna polymerase gene that is c ...200414715303
kaposi sarcoma-associated herpesvirus (kshv) induces heme oxygenase-1 expression and activity in kshv-infected endothelial cells.kaposi sarcoma (ks) is the most common aids-associated malignancy and is characterized by angiogenesis and the presence of spindle cells. kaposi sarcoma-associated herpesvirus (kshv) is consistently associated with all clinical forms of ks, and in vitro infection of dermal microvascular endothelial cells (dmvecs) with kshv recapitulates many of the features of ks, including transformation, spindle cell proliferation, and angiogenesis. to study the molecular mechanisms of kshv pathogenesis, we co ...200414726403
host gene induction and transcriptional reprogramming in kaposi's sarcoma-associated herpesvirus (kshv/hhv-8)-infected endothelial, fibroblast, and b cells: insights into modulation events early during infection.kaposi's sarcoma-associated herpesvirus (kshv/hhv-8) is etiologically linked to the endothelial tumor kaposi's sarcoma and with two lymphoproliferatve disorders, primary effusion lymphoma and multicentric castleman's disease. hhv-8 infects a variety of target cells both in vivo and in vitro, binds to the in vitro target cells via cell surface heparan sulfate, and uses the alpha(3)beta(1) integrin as one of the entry receptors. within minutes of infection, hhv-8 induced the integrin-mediated sign ...200414729610
human herpes virus-8-negative primary effusion lymphoma in a patient with common variable immunodeficiency.primary effusion lymphoma (pel) is a newly described high-grade b cell lymphoma developing in association with human herpes virus type 8 (hhv-8) in human immunodeficiency virus (hiv)-infecting individuals. common variable immunodeficiency (cvid) is a primary immunodeficiency disease characterized by reduced serum immunoglobulin and heterogeneous clinical features. the risk of cancer in cvid patients is increased. here, we describe a pel that developed in the pleural and pericardial cavities of a ...200314738159
regulation and autoregulation of the promoter for the latency-associated nuclear antigen of kaposi's sarcoma-associated herpesvirus.kaposi's sarcoma-associated herpesvirus (kshv) or human herpesvirus 8 has been established as the etiological agent of kaposi's sarcoma and certain aids-associated lymphomas. kshv establishes latent infection in these tumors, invariably expressing high levels of the viral latency-associated nuclear antigen (lana) protein. lana is necessary and sufficient to maintain the kshv episome. it also modulates viral and cellular transcription and has been implicated directly in oncogenesis because of its ...200414742422
kaposi's sarcoma-associated herpesvirus (kshv)/human herpesvirus 8 (hhv-8) as a tumour virus.kaposi's sarcoma-associated herpesvirus (kshv) or human herpesvirus 8 (hhv-8) is present in all clinical variants of kaposi's sarcoma and two lymphoproliferative diseases: primary effusion lymphoma and multicentric castleman's disease (mcd). seroepidemiological studies have proved the link between kshv/hhv-8 infection and development of kaposi's sarcoma. the virus encodes a number of genes homologous to human genes involved in cell proliferation, anti-apoptosis, angiogenesis and cytokine action. ...200314759339
amplification of the kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 lytic origin of dna replication is dependent upon a cis-acting at-rich region and an orf50 response element and the trans-acting factors orf50 (k-rta) and k8 (k-bzip).kaposi's sarcoma-associated herpesvirus (kshv), also known as human herpesvirus 8 (hhv8), has significant sequence homology to epstein-barr virus (ebv). in cell culture, hhv8 is primarily latent, and viral genes associated with lytic replication are not expressed. two lytic origins of dna replication (orilyt) are present within the hhv8 genome and are composed of an at-rich region adjacent to gc-rich dna sequences. we have now identified essential cis- and trans-acting elements required for oril ...200414972523
kshv lana1 binds dna as an oligomer and residues n-terminal to the oligomerization domain are essential for dna binding, replication, and episome persistence.latency-associated nuclear antigen 1 (lana1) binds to kaposi's sarcoma-associated herpesvirus (kshv) terminal repeat (tr) dna to mediate episome replication and persistence. lana1 concentrates at sites of tr dna along mitotic chromosomes, consistent with tethering kshv dna to chromosomes for efficient segregation of episomes to progeny nuclei. we now investigate lana1 c-terminus self-association and dna binding. the tr dna binding domain was localized to lana1 residues 996-1139. scanning deletio ...200414980483
multiple effects of hiv-1 trans-activator protein on the pathogenesis of hiv-1 infection.the hiv-1 trans-activator (tat) protein is proposed as an important factor in the complex hiv-induced pathogenesis of aids. in this paper, multiple effects of this viral protein are described. originally discovered as an intracellular activator of hiv-1 transcription, tat was found to regulate viral reverse transcription as well. trans-activator was found to be secreted by hiv-infected cells and taken up by neighbouring cells. in this way, tat is able to affect both infected and uninfected cells ...200414984439
a polypyrimidine tract facilitates the expression of kaposi's sarcoma-associated herpesvirus vflip through an internal ribosome entry site.we have identified a novel internal ribosome entry site (ires) within a latently expressed kaposi's sarcoma-associated herpesvirus (kshv) gene (vcyclin) that controls the expression of a downstream open reading frame encoding an inhibitor of apoptosis (vflip). this ires is the first such element to be identified in a dna virus and may represent a novel mechanism through which this virus controls gene expression. we have used a dual luciferase reporter assay to identify important sequence element ...200414993645
structural biology of the bcl-2 family of proteins.the proteins of the bcl-2 family are important regulators of programmed cell death. structural studies of bcl-2 family members have provided many important insights into their molecular mechanism of action and how members of this family interact with one another. to date, structural studies have been performed on six bcl-2 family members encompassing both anti- (bcl-x(l), bcl-2, kshv-bcl-2, bcl-w) and pro-apoptotic (bax, bid) members. they all show a remarkably similar fold despite an overall di ...200414996493
wild-type kaposi's sarcoma-associated herpesvirus isolated from the oropharynx of immune-competent individuals has tropism for cultured oral epithelial cells.based on the observation that wild-type kaposi's sarcoma-associated herpesvirus (kshv) dna can be detected in the oral cavity of healthy, immunocompetent individuals, we hypothesized that epithelial cells could be infected in vitro by wild-type (wt) kshv isolated from immunocompetent individuals. primary oral epithelial (p-epi) cells and telomerase-immortalized oral epithelial cells were generated from human gingival tissue and were then infected in vitro with wt kshv isolated from throat wash s ...200415047824
human herpesvirus 8: an update.the discovery of human herpesvirus 8 (hhv-8) has opened a new field in the biology and in the clinical definition of hhv-8-associated diseases. various aspects of epidemiology, laboratory diagnosis and treatment of hhv-8 infection are still controversial. this review will summarise the most recent findings on the modalities of viral transmission in geographic areas where the virus is endemic as compared with those where the infection is sporadic. the studies on the interactions between hhv-8 and ...200415065569
high rate of human herpesvirus-8 seroprevalence in thalassemic patients in italy.the potential risk of acquiring infection by the novel human herpesvirus-8 (hhv-8) through blood derivatives is still debated.200415072763
the kaposi's sarcoma-associated herpesvirus (kshv/hhv-8) k1 protein induces expression of angiogenic and invasion factors.kaposi's sarcoma-associated herpesvirus (kshv/hhv-8) has been linked to kaposi's sarcoma, primary effusion lymphoma, and multicentric castleman's disease. in addition to endothelial cells and b lymphocytes, kshv also has been shown to infect epithelial cells and keratinocytes. the transmembrane glycoprotein k1, encoded by the first open reading frame of kshv, is a signaling protein capable of eliciting b-cell activation. we show that kshv k1 can induce expression and secretion of vascular endoth ...200415087393
human herpes virus 8-negative primary effusion lymphoma (pel) in a patient after repeated chylous ascites and chylothorax.we describe a case of malignant lymphoma which presented in the body cavities without identifiable tumor masses. malignant lymphoma cells showed strong atypia with prominent nuclei and basophilic cytoplasm containing vacuoles. the chromosomes showed diploidy and complex abnormalities including translocations and deletions. we diagnosed this patient with primary effusion lymphoma (pel), even though she tested negative for human herpes virus-8 (hhv-8) which has been suggested to be causally relate ...200415098608
kshv/hhv8-associated lymphoma simulating anaplastic large cell lymphoma.we report a unique, previously undescribed case of kshv/hhv8-associated lymphoma in a 49-year-old hiv-seropositive patient. the cervical lymph node-based lymphoma displayed distinctive characteristic features of preferential sinusoidal infiltrate and anaplastic cellular morphology, closely resembling classic anaplastic large cell lymphoma of the who classification both histologically and immunophenotypically. paraffin immunohistochemical study showed that the lymphoma cells were strongly positiv ...200415105661
hiv-associated primary body-cavity-based lymphoma: clinico-biologic features in three patients diagnosed at the same institution.primary effusion lymphoma (pel) is a recently individualized form of non-hodgkin lymphoma (who classification) that mainly develops in hiv infected males, more frequently in homosexuals and advanced stages of the disease (total cd4+ lymphocyte count below 100-200/ml). occasionally, it appears in others immunodepressive states (such as solid organs postransplant period) and even, although very rarelly, in immunocompetents patients. from a pathogenetic point of view, pel has been related to kaposi ...200415109285
comparison of the rta/orf50 transactivator proteins of gamma-2-herpesviruses.the viral immediate-early transactivator rta/orf50 is necessary and sufficient to initiate kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (kshv/hhv-8) reactivation from latently infected cells. since rta/orf50 is conserved among all known gamma-2-herpesviruses, we investigated whether the murine gamma-68-herpesvirus (mhv-68) and rhesus monkey rhadinovirus (rrv) homologs can functionally substitute for kshv rta/orf50. (i) our comparison of 12 kshv promoters showed that most responded ...200415113928
micronodular kaposi's sarcoma - a new variant of classic-sporadic kaposi's sarcoma.kaposi's sarcoma (ks) in its classic-sporadic form is a rare vascular neoplasm affecting predominantly elderly men of jewish or mediterranean origin. women are very rarely affected by ks. the tumor manifests itself most commonly with brownish macular or infiltrated oval lesions on the lower legs in both genders. human herpesvirus 8 (hhv-8) has recently been demonstrated to be etiologically linked to ks. we report a 51-year-old hiv-seronegative caucasian woman with an unusual, previously not desc ...200415118382
the cxc chemokine receptor encoded by herpesvirus saimiri, ecrf3, shows ligand-regulated signaling through gi, gq, and g12/13 proteins but constitutive signaling only through gi and g12/13 proteins.open reading frame 74 (orf74) of many gamma(2)-herpesviruses encodes a cxc chemokine receptor. the molecular pharmacological profile of orf74 from herpesvirus saimiri, ecrf3, is characterized here and compared with that of the well known orf74 from human herpesvirus 8 (hhv8). the ecrf3 receptor bound the so-called elr (glu-leu-arg) cxc chemokines (125)i-cxcl1/gro alpha, (125)i-cxcl6/gcp-2, and (125)i-cxcl8/interleukin-8 with high affinity; but in contrast to orf74 from hhv8, it did not bind the ...200415155729
kaposi's sarcoma-associated herpesvirus glycoprotein k8.1 is dispensable for virus entry.kaposi's sarcoma-associated herpesvirus (kshv) is considered the etiologic agent of kaposi's sarcoma and several lymphoproliferative disorders. recently, the kshv genome was cloned into a bacterial artificial chromosome and used to construct a recombinant kshv carrying a deletion of the viral interferon regulatory factor gene (f. c. zhou, y. j. zhang, j. h. deng, x. p. wang, h. y. pan, e. hettler, and s. j. gao, j. virol. 76:6185-6196, 2002). the k8.1 glycoprotein is a structural component of th ...200415163732
murine gammaherpesvirus 68 open reading frame 31 is required for viral replication.murine gammaherpesvirus 68 (mhv-68) is genetically related to the human gammaherpesviruses, kaposi's sarcoma-associated herpesvirus (kshv/hhv-8) and epstein-barr virus (ebv). it has been proposed as a model for gammaherpesvirus infection and pathogenesis. open reading frame 31 (orf31) is conserved among the beta- and gammaherpesvirinae subfamily, and there is no known mammalian homologue of this protein. the function of mhv-68 orf31 and its viral homologues has not yet been determined. we descri ...200415163752
a naturally occurring c-terminal truncated isoform of the latent nuclear antigen of kaposi's sarcoma-associated herpesvirus does not associate with viral episomal dna.the latency-associated nuclear antigen (lana) encoded by orf73 of kaposi's sarcoma-associated herpesvirus (kshv) binds to viral episomal dna and nuclear heterochromatin in infected cells. a 3.2 kb transcript in kshv-positive primary effusion lymphoma (pel) cells (bcp-1 and bc-3) encoding a c-terminal truncated form of lana (lana-delta76) has been identified. this transcript has the addition of a poly(a) tail at nt 3264 of orf73 resulting in an in-frame stop codon (taa) effectively truncating lan ...200415166417
use of a multi-virus array for the study of human viral and retroviral pathogens: gene expression studies and chip-chip analysis.since the discovery of human immunodeficiency virus (hiv-1) twenty years ago, aids has become one of the most studied diseases. a number of viruses have subsequently been identified to contribute to the pathogenesis of hiv and its opportunistic infections and cancers. therefore, a multi-virus array containing eight human viruses implicated in aids pathogenesis was developed and its efficacy in various applications was characterized.200415169557
activation of alternative nf-kappa b pathway by human herpes virus 8-encoded fas-associated death domain-like il-1 beta-converting enzyme inhibitory protein (vflip).the kaposi's sarcoma-associated herpesvirus (kshv, also called human herpesvirus 8) has been linked to ks and primary effusion lymphoma (pel) in immunocompromised individuals. we report that pel cell lines have constitutive active alternative nf-kappa b pathway and demonstrate high-level expression of nf-kappa b2/p100 precursor and its processed subunit p52. to elucidate the mechanism of activation of the alternative nf-kappa b pathway in pel cells, we have investigated the role of kshv-encoded ...200415190178
mitotic chromosome-binding activity of latency-associated nuclear antigen 1 is required for dna replication from terminal repeat sequence of kaposi's sarcoma-associated herpesvirus.latency-associated nuclear antigen 1 (lana1) of kaposi's sarcoma-associated herpesvirus (kshv) is implicated in the persistence of the viral genome during latent infection. it has been suggested that lana1 tethers the viral genome to the host chromosome and also participates actively in dna replication from the terminal repeat of kshv. here we show by mutational analysis that the mitotic chromosome-binding activity of lana1 is tightly coupled to its replication activity. thus, kshv appears to ha ...200415194800
utilization of polymerase chain reaction on archival cytologic material: a comparison with fresh material with special emphasis on cerebrospinal fluids.use of the polymerase chain reaction (pcr) for the detection of b- and t-cell clonality, epstein-barr virus (ebv) and human herpes virus 8 (hhv 8) infection is gaining increasing importance as a diagnostic modality. these tests are usually performed on fresh specimens. there are instances when fresh material is not available and there is a clinical utility for the performance of pcr on archival material via slide scrape lysates (ssl). however, the suitability of archival material may be question ...200415195110
involvement of oxidative stress and caspase activation in paclitaxel-induced apoptosis of primary effusion lymphoma cells.paclitaxel has significant antitumor activity in several human tumors, including kaposi's sarcoma (ks). human herpesvirus 8 (hhv-8) is implicated in all forms of kaposi's sarcoma, primary effusion lymphoma (pel), and multicentric castleman's disease (mcd), indicating that it is a dna tumor virus. since it is difficult to culture cell lines derived from ks patients, we used a cell line derived from pel (bcbl-1) to investigate whether oxidative stress is involved in the cytotoxicity of paclitaxel ...200415197489
management of aids-related kaposi sarcoma: advances in target discovery and treatment.kaposi sarcoma (ks) is the most common tumor arising in hiv-infected patients and is considered an aids-defining illness by cdc guidelines. recent advances in the elucidation of the pathogenesis of ks continue to uncover potential targets for therapies. such targets include the ks herpesvirus/human herpesvirus 8 and the processes of angiogenesis and cellular differentiation. five agents are currently approved by the fda for the treatment o ks: alitretinoin gel for topical administration and lipo ...200415199854
modulation of cell signaling pathways by kaposi's sarcoma-associated herpesvirus (kshvhhv-8).kaposi's sarcoma-associated herpesvirus (kshv), also known as human herpesvirus 8, has been associated with the development of kaposi's sarcoma, pleural effusion lymphoma, and multicentric castleman's disease. kshv is a double-stranded dna virus that has been classified as a gammaherpesvirus. the viral genome is approx 160 kb long and encodes for several genes that are involved in cell signaling pathways. these include genes that are unique to the virus as well as viral homologues of cellular ge ...200415211030
kaposi sarcoma herpesvirus-induced cellular reprogramming contributes to the lymphatic endothelial gene expression in kaposi sarcoma.the biology of kaposi sarcoma is poorly understood because the dominant cell type in kaposi sarcoma lesions is not known. we show by gene expression microarrays that neoplastic cells of kaposi sarcoma are closely related to lymphatic endothelial cells (lecs) and that kaposi sarcoma herpesvirus (kshv) infects both lecs and blood vascular endothelial cells (becs) in vitro. the gene expression microarray profiles of infected lecs and becs show that kshv induces transcriptional reprogramming of both ...200415220918
pyogenic granuloma: an unrecognized cause of gastrointestinal bleeding.pyogenic granuloma is a lobular capillary hemangioma that mostly occurs on the skin, but it is also encountered on the mucosal surface of the oral cavity. only a few cases in other parts of the digestive tract have been reported in japanese patients. in this report, two caucasian patients are described, who presented with gastrointestinal bleeding due to the presence of a pyogenic granuloma. one was located in the distal esophagus and could be treated with local excision and laser-photocoagulati ...200415221476
prophylactic strategies before solid-organ transplantation.prophylactic measures prior to organ transplantation are evolving based on recent reports of emerging infectious diseases, as well as an expanded understanding of the epidemiology of familiar infections. this review will highlight developments with potential impact on donor and recipient screening and pretransplant management.200415241081
genotypic profile of human herpesvirus 8 (kaposi's sarcoma-associated herpesvirus) in urine.human herpesvirus 8 (hhv-8) open reading frame k1 sequences amplified from the urine of 5 of 78 (6.4%) infected people in malawi were monotypic. in two people, urinary and oral sequences were genotypically different. comprehensive evaluation of hhv-8 transmission may require characterization of hhv-8 shed both in urine and orally.200415243103
the tumor microenvironment controls primary effusion lymphoma growth in vivo.certain lymphomas in aids patients, such as primary effusion lymphoma (pel), are closely associated with the lymphotropic gamma herpes virus kaposi's sarcoma-associated herpes virus (kshv), also called human herpesvirus 8. the virus is thought to be essential for tumorigenesis, yet systems to investigate pel in vivo are rare. here we describe pel tumorigenesis in a new xenograft model. embedded in matrigel, pel cells formed rapid, well-organized, and angiogenic tumors after s.c. implantation of ...200415256448
kaposi's sarcoma-associated herpesvirus-encoded viral interleukin-6 is secreted and modified differently than human interleukin-6: evidence for a unique autocrine signaling mechanism.viral interleukin-6 (vil-6) is a homolog of cellular il-6 that is encoded by the kaposi's sarcoma-associated herpesvirus (kshv) genome. vil-6 binds to the il-6 signal transducer gp130 without the cooperation of the il-6 high affinity receptor to induce stat3 dna binding and cell proliferation. although vil-6 is believed to be important in the pathogenesis of kshv-induced diseases, its secretion and post-translational modifications have not previously been characterized. pulse-chase analysis reve ...200415258150
interscience conference on antimicrobial agents and chemotherapy - 43rd annual meeting. herpes viruses. 13-17 september 2003, chicago, il, usa. 200315270032
susceptibility to human herpesvirus-8 infection in a healthy population from sardinia is not directly correlated with the expression of hla-dr alleles. 200415270911
virus subversion of protective immunity.the major histocompatibility (mhc) class i antigen presentation pathway plays a pivotal role in immunity to viruses. mhc class i molecules are expressed on the cell surface of all nucleated cells and present peptides derived from intracellular proteins to cytotoxic t lymphocytes (ctls), which then eliminate virally infected cells. however, many viruses have evolved proteins to inhibit the mhc class i pathway, thus enabling virally infected cells to escape ctl lysis. in this review, we summarize ...200415283875
the kaposi's sarcoma-associated herpesvirus complement control protein mimics human molecular mechanisms for inhibition of the complement system.kaposi's sarcoma-associated human herpesvirus (kshv) is thought to cause kaposi's sarcoma, primary effusion lymphoma, and multicentric castleman's disease. previously, we reported that the kshv complement control protein (kcp) encoded within the viral genome is a potent regulator of the complement system; it acts both as a cofactor for factor i and accelerates decay of the c3 convertases (spiller, o. b., blackbourn, d. j., mark, l., proctor, d. g., and blom, a. m. (2003) j. biol. chem. 278, 9283 ...200415304516
human cytomegalovirus ul84 oligomerization and heterodimerization domains act as transdominant inhibitors of orilyt-dependent dna replication: evidence that ie2-ul84 and ul84-ul84 interactions are required for lytic dna replication.human cytomegalovirus (hcmv) ul84 encodes a 75-kda protein required for orilyt-dependent dna replication and interacts with ie2 in infected and transfected cells. ul84 localizes to the nucleus of transfected and infected cells and is found in viral replication compartments. in transient assays it was shown that ul84 can interfere with the ie2-mediated transactivation of the ul112/113 promoter of hcmv. to determine whether ul84 protein-protein interactions are necessary for lytic dna synthesis, w ...200415308715
is plasmablastic lymphoma of the oral cavity an hhv-8-associated disease? 200415316328
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