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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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
classic kaposi's sarcoma of the palm in a metallurgist: role of iron filings in its development? 200312786847
herpesvirus entry: an update. 200312970403
kaposi's sarcoma in a human immunodeficiency virus-negative patient treated with corticosteroid for idiopathic thrombocytopenic purpura. 200312793720
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
stimulation of kaposi's sarcoma-associated herpesvirus viremia during hematopoietic stem cell mobilization with filgrastim.the effects of hematopoietic stem cell (hsc) mobilization on kaposi's sarcoma-associated herpesvirus (kshv) were evaluated in three kshv and human immunodeficiency virus type 1 co-infected subjects. kshv dna was not detected in purified cd34+ cell preparations from the period of filgrastim treatment. however, two of 3 subjects had transiently increased cell-free plasma kshv dna during filgrastim treatment. peak plasma kshv dna (2,600 and 4,300 copies/ml) occurred on day 4 and declined to below t ...200415551282
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
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
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
therapeutic response of hiv-1 subtype c in african patients coinfected with either mycobacterium tuberculosis or human herpesvirus-8.a potential confounding factor in the treatment of human immunodeficiency virus (hiv) infection in africa is the frequent occurrence of opportunistic infections (ois). oi-induced immune activation can interfere with hiv-1 clearance by increasing viral replication and target cell availability.200415633090
immune reconstitution inflammatory syndrome associated with kaposi sarcoma during potent antiretroviral therapy.rapidly progressive kaposi sarcoma (ks) lesions with lymphadenopathy and tissue swelling occurred in a patient during antiretroviral treatment, despite an increased cd4(+) lymphocyte count and decreased hiv-1 level and ks-associated herpesvirus replication, suggesting immune reconstitution inflammatory syndrome. inflammation resolved coincident with decreases in the cd4(+) lymphocyte count during paclitaxel treatment, whereas ks cleared only after prolonged antiretroviral therapy and chemotherap ...200415578411
evidence for both lytic replication and tightly regulated human herpesvirus 8 latency in circulating mononuclear cells, with virus loads frequently below common thresholds of detection.to address whether human herpesvirus 8 (hhv-8) dna in peripheral blood mononuclear cells (pbmcs) might be the product of latent or lytic infection and to shed light on sporadic detection of hhv-8 dna in individuals seropositive for the virus, we studied the frequency of infected cells, total virus load, and virus load per infected cell in pbmcs from men coinfected with hhv-8 and human immunodeficiency virus (hiv), some of whom had kaposi's sarcoma. the low frequencies of infected cells detected ...200415479812
raf-induced vascular endothelial growth factor augments kaposi's sarcoma-associated herpesvirus infection.recombinant green fluorescent protein encoding kaposi's sarcoma-associated herpesvirus (rkshv.152) infection of beta-estradiol stimulated human foreskin fibroblasts (hff) or hff/deltab-raf([ff]):er (expressing a weaker form of b-raf) could be enhanced to levels comparable to that of hff/deltab-raf([dd]):er cells by pretreating cells with soluble vascular endothelial growth factor (vegf). conversely, vegf expression and infection efficiency typically observed in beta-estradiol stimulated hff/delt ...200415542692
the dna architectural protein hmgb1 facilitates rta-mediated viral gene expression in gamma-2 herpesviruses.replication and transcription activator (rta), an immediate-early gene product of gamma-2 herpesviruses including kaposi's sarcoma-associated herpesvirus (kshv) and murine gamma herpesvirus 68 (mhv-68), plays a critical role in controlling the viral life cycle. rta acts as a strong transcription activator for several downstream genes of kshv and mhv-68 through direct dna binding, as well as via indirect mechanisms. hmgb1 (also called hmg-1) protein is a highly conserved nonhistone chromatin prot ...200415542646
susceptibility to human herpesvirus-8 infection in a healthy population from sardinia is not directly correlated with the expression of hla-dr alleles. 200415270911
the rationale for pathogen-inactivation treatment of blood components.blood transfusion provides an ideal portal of entry for microorganisms. although current residual risks of microbial infection by transfusion are extremely low in the developed world, the requirements for even safer blood are paradoxically increasing. such requirements are partly a legacy of the tragic transmissions of human immunodeficiency virus (hiv) by blood early in the acquired immunodeficiency syndrome pandemic and are legally expressed in consumer protection laws imposing strict product ...200415615254
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
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
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
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
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
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
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
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
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
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
aids, multicentric castleman's disease, and plasmablastic leukemia: report of a long-term survival.plasmablastic leukemia (pl) as a complication of human herpes virus 8 (hhv8)-associated castleman's disease is marked by a rapid and fatal outcome. in patients with aids, survival of 7 to 14 days after diagnosis has been reported. prompt splenectomy and chemotherapy might lead to a significant survival benefit. here we report a case of long-term survival in a patient with aids and multicentric castleman's disease (mcd) complicated by pl.200415624895
rna-based gene transfer for adult stem cells and t cells.electroporation of mrna has become an established method for gene transfer into dendritic cells for immunotherapeutic purposes. however, many more cell types and applications might benefit from an efficient mrna-based gene transfer method. in this study, we investigated the potential of mrna-based gene transfer to induce short-term transgene expression in adult stem cells and activated t cells, based on electroporation with mrna encoding the enhanced green fluorescent protein. the results show e ...200415385941
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
viral load of human herpesvirus 8 (hhv-8) in the circulatory blood cells correlates with clinical progression in a patient with hhv-8-associated solid lymphoma with aids-associated kaposi's sarcoma.we encountered a case of a rapidly progressive hhv-8-associated solid lymphoma with aids-associated kaposi's sarcoma (ks). hhv-8 dna load in whole blood cells was analyzed quantitatively by real-time pcr using amplification of the hhv-8-encoded orf26 gene. ours is the first observation that the rapid increase in the hhv-8 viral load (from 1.9x10(4) copies/microg to 1.6x10(6) copies/microg in 40 days) in conjunction with low cd4+ cell counts was accompanied by an accelerated clinical disease prog ...200415512828
disruption of kaposi's sarcoma-associated herpesvirus latent nuclear antigen leads to abortive episome persistence.latent nuclear antigen (lna) is implicated in kaposi's sarcoma-associated herpesvirus (kshv) episome persistence. lna colocalizes with kshv episomes on chromosomes in metaphase, and it maintains the stability and replication of kshv terminal repeat-containing plasmids. in this study, we examined the function of lna in episome persistence in the context of full-length kshv genome by mutagenesis analysis. we generated a kshv mutant, bac36-deltalna, with lna disrupted by transposon-based mutagenesi ...200415452232
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
kaposi's sarcoma-associated herpesvirus infection of blood endothelial cells induces lymphatic differentiation.kaposi's sarcoma-associated herpesvirus (kshv) is necessary for ks, a highly vascularized tumor predominated by endothelial-derived spindle cells that express markers of lymphatic endothelium. following kshv infection of time cells, an immortalized human dermal microvascular endothelial cell (dmvec) line, expression of many genes specific to lymphatic endothelium, including vegfr3, podoplanin, lyve-1, and prox-1, is significantly increased. increases in vegfr3 and podoplanin protein are also dem ...200415380353
orc, mcm, and histone hyperacetylation at the kaposi's sarcoma-associated herpesvirus latent replication origin.the viral genome of kaposi's sarcoma-associated herpesvirus (kshv) persists as an extrachromosomal plasmid in latently infected cells. the kshv latency-associated nuclear antigen (lana) stimulates plasmid maintenance and dna replication by binding to an approximately 150-bp region within the viral terminal repeats (tr). we have used chromatin immunoprecipitation assays to demonstrate that lana binds specifically to the replication origin sequence within the kshv tr in latently infected cells. th ...200415507644
the kaposi's sarcoma-associated herpesvirus k-bzip protein represses transforming growth factor beta signaling through interaction with creb-binding protein.kaposi's sarcoma (ks)-associated herpesvirus (kshv) is involved in the pathogenesis of ks, primary effusion lymphoma, and multicentric castleman's disease. k-bzip, the protein encoded by the open reading frame k8 of kshv, is a member of the basic region-leucine zipper family of transcription factors. we studied the mechanisms that underlie kshv-induced oncogenesis by investigating whether k-bzip perturbs signaling through transforming growth factor beta (tgf-beta), which inhibits proliferation o ...200415467747
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
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
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
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