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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
t- and b-cell clonality and frequency of human herpes viruses-6, -8 and epstein barr virus in angioimmunoblastic t-cell lymphoma.angioimmunoblastic t-cell lymphoma (t-ail) is a peripheral t-cell lymphoma of unknown etiology. previous clonality studies have shown a heterogeneous composition of this disease with varying restrictions of b- and t-cell populations in the tumour. for the first time in a single study and in the same pathological materials, we have analysed, lymphoid cell clonality and occurrence of human herpes viruses and epstein barr virus. of 18 cases 12 (66.6%) had clonal t- and three (16.6%) had clonal b-ce ...200416134192
interscience conference on antimicrobial agents and chemotherapy - 43rd annual meeting. herpes viruses. 13-17 september 2003, chicago, il, usa. 200315270032
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
the kaposi's sarcoma-associated herpesvirus g protein-coupled receptor has broad signaling effects in primary effusion lymphoma cells.kaposi's sarcoma-associated herpesvirus (kshv/human herpesvirus 8 [hhv-8]) is a gamma-2-herpesvirus responsible for kaposi's sarcoma as well as primary effusion lymphoma (pel). kshv is a lymphotropic virus that has pirated many mammalian genes involved in inflammation, cell cycle control, and angiogenesis. among these is the early lytic viral g protein-coupled receptor (vgpcr), a homologue of the human interleukin-8 (il-8) receptor. when expressed, vgpcr is constitutively active and can signal v ...200312477810
kaposi's sarcoma-associated herpesvirus induces the phosphatidylinositol 3-kinase-pkc-zeta-mek-erk signaling pathway in target cells early during infection: implications for infectivity.human herpesvirus 8 (hhv-8) is implicated in the pathogenesis of kaposi's sarcoma. hhv-8 envelope glycoprotein b (gb) possesses the rgd motif known to interact with integrin molecules, and hhv-8 infectivity was inhibited by rgd peptides, by antibodies against alpha3 and beta1 integrins, and by soluble alpha3beta1 integrin (s. m. akula, n. p. pramod, f.-z. wang, and b. chandran, cell 108:407-419, 2002). anti-gb antibodies immunoprecipitated the virus alpha3 and beta1 complexes, and virus-binding ...200312502866
dissolution of the lymphoid follicle is a feature of the hhv8+ variant of plasma cell castleman's disease.the plasma cell variant of castleman's disease (pcd) may occur in a variety of clinical settings. one recently delineated type of pcd is caused by human herpesvirus 8 (hhv8) infection. lymph nodes from 25 patients with pcd, including six hhv8+ and 19 hhv8- cases, were studied. three patients with hhv8+ pcd were also infected with human immunodeficiency virus-1. features common to all cases were interfollicular plasmacytosis and variably hyperplastic and regressed follicle germinal centers. featu ...200312502931
a g protein-coupled receptor encoded by rhesus rhadinovirus is similar to orf74 of kaposi's sarcoma-associated herpesvirus.rhesus rhadinovirus (rrv) is a gamma-2 herpesvirus and is the rhesus macaque homologue of human herpesvirus 8 (hhv-8), also known as kaposi's sarcoma-associated herpesvirus. dna sequence analysis of rrv indicates that it shares numerous open reading frames (orfs) with hhv-8, including one (orf74) encoding a seven-transmembrane-spanning g protein-coupled receptor (gpcr) with similarity to cellular chemokine receptors. examination of the predicted amino acid sequence of rrv orf74 reveals that it e ...200312525607
aids-related malignancies.immunodeficiency alters the risk of cancer. specific types of immune dysfunction are associated with different tumor risks, but most tumors are related to oncogenic viruses. in acquired immunodeficiency due to the human immunodeficiency virus (hiv), hiv itself rarely directly causes cancer; rather, it provides the immunologic background against which other viruses can escape immune control and induce tumors. the most common malignancies are kaposi's sarcoma and non-hodgkin's lymphoma. this chapt ...200312525676
risk factors for kaposi's sarcoma in men seropositive for both human herpesvirus 8 and human immunodeficiency virus.to identify risk factors for kaposi's sarcoma (ks) among men seropositive for both human herpesvirus 8 (hhv-8) and hiv.200312545082
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
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
kaposi's sarcoma-like tumors in a human herpesvirus 8 orf74 transgenic mouse.the product of human herpesvirus 8 (hhv-8) open reading frame 74 (orf74) is related structurally and functionally to cellular chemokine receptors. orf74 activates several cellular signaling pathways in the absence of added ligands, and nih 3t3 cells expressing orf74 are tumorigenic in nude mice. we have generated a line of transgenic (tg) mice with orf74 driven by the simian virus 40 early promoter. a minority (approximately 30%) of the tg mice, including the founder, developed tumors resembling ...200312552002
the latency-associated nuclear antigen of kaposi's sarcoma-associated herpesvirus permits replication of terminal repeat-containing plasmids.the latency-associated nuclear antigen (lana) of kaposi's sarcoma-associated herpesvirus can associate with mitotic chromosomes and promote latent episome maintenance and segregation. here we report that lana also mediates the replication of plasmid dnas bearing viral terminal repeats. the predicted secondary structure of lana's c terminus reveals striking similarity to the known structure of the dna-binding domain of epstein-barr virus ebna1, despite the absence of primary sequence homology bet ...200312552022
review of the distribution of kaposi's sarcoma-associated herpesvirus (kshv) in africa in relation to the incidence of kaposi's sarcoma.in the years before human immunodeficiency virus (hiv) infection, the incidence of kaposi's sarcoma varied markedly across the african continent, and it was a disease primarily affecting men. in contrast, the evidence reviewed here shows that the causal virus-kaposi's sarcoma associated herpesvirus (kshv)-is prevalent in many african countries, including places where kaposi's sarcoma was almost unknown before hiv, and that it is as common in women as in men. therefore, the geographical distribut ...200312556950
hhv 8 seroprevalence and transmission within albanian family groups.the recently discovered human herpesvirus 8 (hhv 8) is associated with all clinical forms of kaposi's sarcoma. while early research suggested that the virus was transmitted sexually and that it was present only in ks patients, more recent studies seem to show that infection with the virus is more common than once thought, presenting differing distribution patterns in different geographical areas. in this study we analyze seroprevalence and transmission of hhv 8 in a sample of 86 family groups fr ...200312578305
human herpesvirus 8: is it time for routine surveillance in pediatric solid organ transplant recipients to prevent the development of kaposi's sarcoma? 200312581319
c-mir, a human e3 ubiquitin ligase, is a functional homolog of herpesvirus proteins mir1 and mir2 and has similar activity.kaposi's sarcoma associated-herpes virus encodes two proteins, mir (modulator of immune recognition) 1 and 2, which are involved in the evasion of host immunity. mir1 and 2 have been shown to function as an e3 ubiquitin ligase for immune recognition-related molecules (e.g. major histocompatibility complex class i, b7-2, and icam-1) through the bks (bovine herpesvirus 4, kaposi's sarcoma associated-herpes virus, and swinepox virus) subclass of plant homeodomain (phd) domain, termed the bks-phd do ...200312582153
human herpesvirus 8 envelope glycoprotein b mediates cell adhesion via its rgd sequence.human herpesvirus 8 (hhv-8) or kaposi's sarcoma-associated herpesvirus, implicated in the pathogenesis of kaposi's sarcoma, utilizes heparan sulfate-like molecules to bind the target cells via its envelope-associated glycoproteins gb and gpk8.1a. hhv-8-gb possesses the arg-gly-asp (rgd) motif, the minimal peptide region of many proteins known to interact with subsets of host cell surface integrins. hhv-8 utilizes alpha3beta1 integrin as one of the receptors for its entry into the target cells vi ...200312584338
infection with human herpesvirus type 8 and kaposi's sarcoma in a central italian area formerly endemic for malaria.to estimate the prevalence of infection with human herpes virus type 8 (hhv8) and the incidence of kaposi's sarcoma among hhv8-infected individuals, we conducted a population-based, cross-sectional study in latina. this area of central italy was formerly endemic for malaria and it is now covered by a population-based cancer registry.200312590333
posttransplantation kaposi sarcoma-experience in a patient receiving fk-506 and mmf. 200312591389
factors associated with human herpesvirus type 8 infection in an injecting drug user cohort.human herpesvirus type 8 (hhv-8) has been infrequently studied in injecting drug user (idu) populations.200312616135
three-dimensional localization of porf65 in kaposi's sarcoma-associated herpesvirus capsid.of the six herpesvirus capsid proteins, the smallest capsid proteins (scps) share the least sequence homology among herpesvirus family members and have been implicated in virus specificity during infection. the herpes simplex virus-1 (hsv-1) scp was shown to be horn shaped and to specifically bind the upper domain of each major capsid protein in hexons but not in pentons. in kaposi's sarcoma-associated herpesvirus (kshv), the protein encoded by the orf65 gene (porf65) is the putative scp but its ...200312634386
viral coinfections among african children infected with human immunodeficiency virus type 1.city-dwelling children from kenya who were infected with human immunodeficiency virus type 1 (hiv-1) were tested for coinfection with cytomegalovirus (cmv), human t cell lymphotropic viruses 1 and 2, kaposi sarcoma-associated herpesvirus (kshv), or hepatitis b, c, and g viruses. all children were found to be coinfected with cmv, whereas 5% had hepatitis g virus coinfection and 15% had kshv coinfection. a protective role for hepatitis g virus cannot be excluded but likely affects only a minority ...200312652394
detection of hhv-8 sequences and antigens in a malt lymphoma associated with sjögren's syndrome.we describe the case of a bilateral parotid mucosa-associated lymphoid tissue (malt) lymphoma associated with 2 years history of sjögren's syndrome (ss), which was linked to human herpes virus 8 (hhv-8) infection. using polymerase chain reaction (pcr) assay hhv-8 sequences were detectable in the lymphoma tissue of both sides. serologic testing of the patient revealed hhv-8 antibodies in enzyme-linked immunosorbent assay (elisa) and immunofluorescence assay (ifa). immunohistologic staining with t ...200312653865
seroprevalence of human herpesvirus 8 among injection drug users in san francisco.the association between injection drug use and human herpesvirus 8 (hhv-8) was examined to investigate bloodborne transmission of the virus. in all, 1905 injection drug users (idus) enrolled in a cross-sectional study were tested for k8.1 antibodies to hhv-8 lytic antigen. logistic regression was used to adjust for demographic and sexual behavior variables. hhv-8 seroprevalence was 10% among women, 10% among heterosexual men, and 23% among men who have sex with men. in adjusted analyses, hhv-8 s ...200312660944
hhv-8 dna sequences in the peripheral blood and skin lesions of an hiv-negative patient with multiple eruptive dermatofibromas: implications for the detection of hhv-8 as a diagnostic marker for kaposi's sarcoma.multiple eruptive dermatofibroma (medf) is a rare disorder seen in immunocompromised patients, simulating kaposi's sarcoma (ks). whereas ks is strongly associated with human herpesvirus 8 (hhv-8), the virus has never been detected in medf until now.200312673078
cross-talk between human herpesvirus 8 and the transactivator protein in the pathogenesis of kaposi's sarcoma in hiv-infected patients.aids-associated kaposi's sarcoma (aks) is particularly aggressive and it is one of the principal neoplasms in regions of africa affected by both high endemic hhv8 and epidemic hiv infection. in this study, serum samples from 18 patients with kaposi's sarcoma from tanzania, mostly males (n = 15 vs 3), were subjected to analysis with respect to hhv8-dna load and antibody spectrum against the hiv-1 tat protein. of the 18 patients, 14 were hiv-1-positive. the median hhv8 virus load in the hiv-1-posi ...200312680174
pathogenesis and manifestations of human herpesvirus-8-associated disorders.human herpesvirus-8 (hhv-8), a recently discovered oncogenic human virus, is consistently associated with kaposi's sarcoma (ks), primary effusion lymphoma (pel), and multicentric castleman's disease (mcd). these disorders occur more frequently, but not exclusively, in human immunodeficiency virus (hiv)-infected individuals, and exhibit more aggressive clinical courses when developing in the setting of acquired immunodeficiency syndrome (aids). one of the most intriguing aspects of hhv-8-related ...200312704591
kaposi's sarcoma: aetiopathogenesis, histology and clinical features.kaposi's sarcoma (ks) represents today one of the most common skin cancers in transplanted mediterranean subjects and, since the epidemic of human immunodeficiency virus/acquired immune deficiency syndrome, in young unmarried single men. the disease has been associated with the recent identified human herpesvirus (hhv)-8 or ks herpesvirus and its incidence in the general population shows a north to south gradient that parallels the hhv-8 increasing prevalence from nordic countries to sub-saharan ...200312705742
[neoplastic manifestations of hiv infection].the incidence of malignancies has increased in conjunction with epidemic of human immunodeficiency virus (hiv) disease and they are currently considered acquired immunodeficiency syndrome (aids)-defining conditions. approximately 40% of all patients with aids have developed cancer during the course of hiv infections. further, as survival has improved in hiv disease, the incidence of these malignancies has increased. the main malignancies noted are kaposi's sarcoma, non-hodgkin's lymphoma, hodgki ...200312708185
relationship of kaposi sarcoma (ks)-associated herpesvirus viremia and ks disease in zimbabwe.the relationship between kaposi sarcoma-associated herpesvirus (kshv) viremia and ks disease was investigated in 500 subjects who received treatment in harare, zimbabwe. subjects were grouped by results of human immunodeficiency virus (hiv) type 1 serological tests, ks diagnosis, and ks clinical stage. the plasma kshv dna concentration was associated with concomitant ks and hiv-1 infection (aids-ks; p<.001) and aids-ks clinical stage (p=.01). plasma kshv dna levels were greater in aids-ks than i ...200312715309
kaposi's sarcoma--an update. 200312716490
kaposi's sarcoma-associated herpesvirus lytic origin (ori-lyt)-dependent dna replication: identification of the ori-lyt and association of k8 bzip protein with the origin.herpesviruses utilize different origins of replication during lytic versus latent infection. latent dna replication depends on host cellular dna replication machinery, whereas lytic cycle dna replication requires virally encoded replication proteins. in lytic dna replication, the lytic origin (ori-lyt) is bound by a virus-specified origin binding protein (obp) that recruits the core replication machinery. in this report, we demonstrated that dna sequences in two noncoding regions of the kaposi's ...200312719550
the latency-associated nuclear antigen homolog of herpesvirus saimiri inhibits lytic virus replication.herpesvirus saimiri (hvs), a t-lymphotropic tumor virus of neotropical primates, and the kaposi's sarcoma-associated human herpesvirus 8 (kshv) belong to the gamma-(2)-herpesvirus (rhadinovirus) subfamily and share numerous features of genome structure and organization. the kshv latency-associated nuclear antigen (lana) protein appears to be relevant for viral persistence, latency, and transformation. it binds to dna, colocalizes with viral episomal dna, and presumably mediates efficient persist ...200312719584
split genes and their expression in kaposi's sarcoma-associated herpesvirus.a split or interrupted gene is defined as a gene consisting of introns and exons. removal (splicing) of the intron(s) from a primary transcript (pre-mrna) is essential for creating a mrna. initial assignment of a potential protein coding region in the kshv genome was based on the initiation codon context and predicted protein size larger than 100 amino acids, but the gene discontinuity was disregarded. experimental investigation of the assigned orfs has demonstrated that there are up to 25 split ...200312740832
host range of kaposi's sarcoma-associated herpesvirus in cultured cells.difficulties in efficiently propagating kaposi's sarcoma-associated herpesvirus (kshv) in culture have generated the impression that the virus displays a narrow host range. here we show that, contrary to expectation, kshv can establish latent infection in many adherent cell lines, including human and nonhuman cells of epithelial, endothelial, and mesenchymal origin. (paradoxically, the only lines in which we have not observed successful latent infection are cultured lymphoma cell lines.) in most ...200312743304
immunoblastic lymphoma in persons with aids-associated kaposi's sarcoma: a role for kaposi's sarcoma-associated herpesvirus.kaposi's sarcoma-associated herpesvirus, the viral agent of kaposi's sarcoma, is associated with two lymphoproliferative disorders: primary effusion lymphoma and multicentric castleman's disease. to identify other lymphoproliferative conditions linked with kaposi's sarcoma-associated herpesvirus, we studied non-hodgkin's lymphomas arising in individuals with aids-associated kaposi's sarcoma. formalin-fixed tissues from 24 such lymphomas were examined. as expected, two primary effusion lymphomas ...200312748248
natural killer cell-type body cavity lymphoma following chronic active epstein-barr virus infection.we describe a 69-year-old female who developed natural killer cell-type body cavity lymphoma following chronic active epstein-barr virus (caebv) infection. examination of the patient's pleural effusion revealed large abnormal lymphocytes, which were cd2(+), cd7(+), cd30(+), cd56(+), cd3(-), and cd4(-). no rearrangement of t cell receptor genes was detected. clonal proliferation of epstein-barr virus (ebv)-infected cells in pleural effusion was demonstrated by southern blot hybridization analysis ...200312749015
causality or coincidence: may the slow disappearance of helminths be responsible for the imbalances in immune control mechanisms?intestinal infection continues to be a problem worldwide and helminths, which currently infect billions of individuals, are primary culprits. the major burden of disease falls on the populations of developing countries, given that over the last four to five decades helminth infections are disappearing in industrialized societies. in developing countries, a major source of immunomodulatory signals in post-natal life are parasites, particularly helminths, which, unlike most bacteria and viruses, s ...200312756068
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
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
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
hyaline vascular castleman's disease: a case report and brief review of the literature.we describe a 27-year-old female with a mesenterial localisation of the hyaline vascular type of castleman's disease. a review of the literature is given with emphasis on the different pathogenesis of the subtypes. the hyaline vascular type is a disorder of stromal cells, which can be complicated by the development of soft tissue sarcomas. the plasma cell type is a plasma cell disorder with elevated levels of interleukin-6 (il-6). in the multicentric type, infection with human herpes virus-8 (hh ...200212685494
human immunodeficiency virus type-1 activates lytic cycle replication of kaposi's sarcoma-associated herpesvirus through induction of kshv rta.human immunodeficiency virus type-1 (hiv-1) infection dramatically increases the risk of development of kaposi's sarcoma (ks) in individuals infected with kaposi's sarcoma-associated herpesvirus (kshv). in a primary effusion lymphoma (pel) tissue culture model system, hiv-1 replication potently induced the lytic replication of kshv and led to the secretion of soluble factors capable of inducing lytic kshv replication in bystander cells. here we demonstrate that hiv induces kshv lytic replication ...200212083825
detection of kaposi's sarcoma herpesvirus dna sequences in pericardial fluid in a patient with multicentric castleman's disease. 200212084108
elevated virus loads of kaposi's sarcoma-associated human herpesvirus 8 predict kaposi's sarcoma disease progression, but elevated levels of human immunodeficiency virus type 1 do not.kaposi's sarcoma-associated herpesvirus (kshv) is found in kaposi's sarcoma (ks), multicentric castleman's disease, and primary effusion lymphomas. to prospectively evaluate kshv load as a biomarker for ks clinical status and prognosis in a cohort of men with aids-related ks, 2 quantitative polymerase chain reaction (pcr) assays were developed and tested to determine kshv peripheral blood mononuclear cell (pbmc) virus loads. most patients (13/15) with good-prognosis ks had < or =1.5 log kshv cop ...200212085319
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