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an unusual dependence of human herpesvirus-8 glycoproteins-induced cell-to-cell fusion on heparan sulfate.human herpesvirus-8 (hhv-8) is known to interact with cell surface heparan sulfate (hs) for entry into a target cell. here we investigated the role of hs during hhv-8 glycoproteins-induced cell fusion. interestingly, the observed fusion demonstrated an unusual dependence on hs as evident from following lines of evidence: (1) a significant reduction in cell-to-cell fusion occurred when target cells were treated with heparinase; (2) in a competition assay, when the effector cells expressing hhv-8 ...200919747451
9-(2-c-cyano-2-deoxy-beta-d-arabino-pentofuranosyl)guanine, a potential antitumor agent against b-lymphoma infected with kaposi's sarcoma-associated herpesvirus.several 9-(2-c-cyano-2-deoxy-l-beta-d-arabino-pentofuranosyl)purine derivatives were tested against kaposi's sarcoma-associated herpesvirus (kshv)-infected primary effusion lymphoma (pel) cells. the guanine derivative (2, cndag) as well as the 2-amino-6-substituted-purine derivatives 3, 4 and 5 inhibited kshv-positive cell growth but showed no cytotoxicity against kshv-negative cells at >15 mum concentrations. therefore, it was found that compounds 2, 3, 4 and 5 showed selective cytotoxicity aga ...200919749277
hhv8-positive, hiv-negative multicentric castleman's disease: early and sustained complete remission with rituximab therapy without reactivation of kaposi sarcoma.multicentric castleman's disease (mcd) is a rare lymphoproliferative disorder with systemic symptoms and poor prognosis and is characterized by an abnormal proliferation of polyclonal plasmablasts in the mantle zone of b-cell follicles. the disease is found primarily in chronic hiv carriers and is usually strictly associated with human herpes virus type 8 (hhv-8) coinfection, which is believed to play a key role in the pathogenesis of mcd. the disease is also diagnosed in hiv-negative patients, ...200919756920
the impact of preexisting or acquired kaposi sarcoma herpesvirus infection in kidney transplant recipients on morbidity and survival.the impact of preexisting or acquired kaposi sarcoma herpesvirus (kshv) infection in kidney transplant recipients was evaluated in a prospective study. serum collected from kidney donors and recipients before transplantation were tested for antibodies against kshv latent nuclear antigen. three groups of recipients were defined: group a (kshv+), group b (kshv-, kshv+ donor) and group c (donor and recipient kshv-). blood was collected from recipients, every 3 months for 3 years, for kshv viremia ( ...200919775317
mother-to-child hiv and hhv-8 transmission in neonates at saint camille medical centre in burkina faso.in sub-saharan africa, many hiv infected people are co-infected with human herpes virus 8 (hhv-8). therefore, the present study aimed to: (1) identify the pregnant women co-infected by hiv and hhv-8 at saint camille medical centre; (2) use three molecules (zidovudine, nevirapine and lamivudine) to interrupt the vertical transmission of hiv and (3) use the pcr technique to diagnose children, who were infected by these viruses, in order to offer them an early medical assistance. a total of 107 pre ...200919777784
electrochemotherapy-induced virus disappearance in hhv-8-positive skin nodules of kaposi sarcoma: first histological and immunohistochemical demonstration of efficacy. 201019778362
laryngeal inflammatory myofibroblastic tumors: different clinical appearance and histomorphologic presentation of one entity.inflammatory myofibroblastic tumors (imfts) of the larynx are rare. we report the clinical presentation, histomorphology, and new molecular findings of 2 cases.201019787794
role of orf74-encoded viral g protein-coupled receptor in human herpesvirus 8 lytic replication.the human herpesvirus 8 (hhv-8) viral g protein-coupled receptor (vgpcr) has been implicated in virus-associated disease pathogenesis due principally to its ability to induce the production of angiogenic cytokines involved in this process. however, the role of the vgpcr in normal virus biology is understudied and remains unknown. here we provide evidence from vgpcr gene knockout and depletion experiments that vgpcr is a positive regulator of hhv-8 productive replication and, through experimental ...200919793819
kaposi sarcoma herpes virus-associated hemophagocytic syndrome complicated by multicentric castleman disease and kaposi sarcoma in a hiv-negative immunocompetent patient: an autopsy case.kaposi sarcoma herpes virus (kshv), also known as human herpesvirus-8, plays an important role in the pathogenesis of kaposi sarcoma (ks), multicentric castleman disease (mcd) of the plasma cell type, and primary effusion lymphoma. kshv is rarely associated with the hemophagocytic syndrome (hps), but when it does occur, it most occurs in immunocompromised patients. we report herein an unusual case of kshv-associated hps in an immunocompetent patient. a previously healthy 62-yr-old male was refer ...200919795003
non-human primate model of kaposi's sarcoma-associated herpesvirus infection.since kaposi's sarcoma-associated herpesvirus (kshv or human herpesvirus 8) was first identified in kaposi's sarcoma (ks) lesions of hiv-infected individuals with aids, the basic biological understanding of kshv has progressed remarkably. however, the absence of a proper animal model for kshv continues to impede direct in vivo studies of viral replication, persistence, and pathogenesis. in response to this need for an animal model of kshv infection, we have explored whether common marmosets can ...200919798430
follicular dendritic cells in multicentric castleman disease present human herpes virus type 8 (hhv8)-latent nuclear antigen 1 (lana1) in a proportion of cases and is associated with an enhanced t-cell response.multicentric castleman disease (mcd) is a rare human herpes virus type 8 (hhv8)-associated lymphoproliferative disorder that occurs more frequently in patients infected with human immunodeficiency virus (hiv). in tissue samples, hhv8-infected plasmablasts localise to the mantle zones of the lymphoid follicles. we revisited the immunohistological features in 25 lymph node (ln) and three spleen samples of mcd. in five (20%) ln and one (33%) spleen sample, hhv8 latent nuclear antigen 1 (lana1) stai ...201019799625
predictors of immune reconstitution inflammatory syndrome-associated with kaposi sarcoma in mozambique: a prospective study.the impact and relevance of immune reconstitution inflammatory syndrome-associated with kaposi sarcoma (iris-ks) has not been assessed in sub-saharan african countries, where the bulk of hiv-1 and ks-associated herpesvirus (kshv) coinfection occurs. understanding the risk factors for developing iris-ks would aid in the identification and in the improvement of clinical management for high-risk patients.201019801945
kshv manipulates notch signaling by dll4 and jag1 to alter cell cycle genes in lymphatic endothelia.increased expression of notch signaling pathway components is observed in kaposi sarcoma (ks) but the mechanism underlying the manipulation of the canonical notch pathway by the causative agent of ks, kaposi sarcoma herpesvirus (kshv), has not been fully elucidated. here, we describe the mechanism through which kshv directly modulates the expression of the notch ligands jag1 and dll4 in lymphatic endothelial cells. expression of kshv-encoded vflip induces jag1 through an nfkappab-dependent mecha ...200919816565
differentiating hiv-associated non-hodgkin's lymphomas with similar plasmacellular differentiation. 200919839364
nucleolar disruption impairs kaposi's sarcoma-associated herpesvirus orf57-mediated nuclear export of intronless viral mrnas.kaposi's sarcoma-associated herpesvirus (kshv) orf57 plays a pivotal role in mediating the nuclear export of kshv intronless transcripts. we demonstrate that orf57 localises and dynamically trafficks through the nucleolus. to assess if nucleolar shuttling of orf57 is important for the export of intronless viral mrna, the ability of orf57 to export mrna was assessed in cells where the nucleolus was disrupted using actinomycin d or drb. we show that rapid disorganisation of the nucleolus was accom ...200919850040
inflammatory myofibroblastic tumors in childhood: a report from the italian cooperative group studies.inflammatory myofibroblastic tumors (imts) are myofibroblastic lesions with unpredictable biologic behavior that occur at a young age. for this report, the authors investigated clinicopathologic features in a series of pediatric imts. the objective of the study was to identify morphologic or immunohistochemical prognostic markers and the possible pathogenic role of human herpes virus 8 (hhv-8).201019852031
inhibition of the phosphatidylinositol 3-kinase-akt pathway enhances gamma-2 herpesvirus lytic replication and facilitates reactivation from latency.cellular signalling pathways are critical in regulating the balance between latency and lytic replication of herpesviruses. here, we investigated the effect of the phosphatidylinositol 3-kinase (pi3k)-akt pathway on replication of two gamma-2 herpesviruses, murine gammaherpesvirus-68 (mhv-68) and human herpesvirus-8/kaposi's sarcoma-associated herpesvirus (hhv-8/kshv). we found that de novo infection of mhv-68 induced pi3k-dependent akt activation and the lytic replication of mhv-68 was enhanced ...201019864499
c-kit (cd117) expression in classic kaposi's sarcoma.kaposi's sarcoma is a multicentric, low-grade, vascular neoplasia. human herpesvirus 8 is associated with all epidemiological forms of ks and has been shown in vitro to induce the tyrosine receptor kinase c-kit in infected cells.201019874361
in-depth analysis of kaposi's sarcoma-associated herpesvirus microrna expression provides insights into the mammalian microrna-processing machinery.we have used deep sequencing to analyze the pattern of viral microrna (mirna) expression observed in the b-cell line bc-3, which is latently infected with kaposi's sarcoma-associated herpesvirus (kshv). we recovered 14.6 x 10(6) total mirna cdna reads, of which a remarkable 92% were of kshv origin. we detected 11 kshv mirnas as well as all 11 predicted mirna or passenger strands from the mirna duplex intermediate. one previously reported kshv mirna, mir-k9, was found to be mutationally inactivat ...201019889781
molecular and clinical assessment in the treatment of aids kaposi sarcoma with valproic acid.the aids malignancy consortium undertook a pilot trial of valproic acid among patients with aids-associated kaposi sarcoma (ks). treatment was associated with low toxicity, but the ks clinical response and ks herpesvirus lytic induction rates were not sufficiently high to meet predefined criteria for efficacy.200919911999
1 alpha,25-dihydroxyvitamin d3 and its tx527 analog inhibit the growth of endothelial cells transformed by kaposi sarcoma-associated herpes virus g protein-coupled receptor in vitro and in vivo.the kaposi sarcoma-associated herpes virus-g protein-coupled receptor is a key molecule in the pathogenesis of kaposi sarcoma, playing a central role in promoting vascular endothelial growth factor-driven angiogenesis and spindle cell proliferation. we studied the effects of 1 alpha,25-dihydroxyvitamin d(3) [1 alpha,25(oh)(2)d(3)] and the analog tx527 on the proliferation of endothelial cells (svecs) and svecs transformed by the viral g protein-coupled receptor (svec-vgpcr). 1 alpha,25(oh)(2)d(3 ...201019915163
the orf59 dna polymerase processivity factor homologs of old world primate rv2 rhadinoviruses are highly conserved nuclear antigens expressed in differentiated epithelium in infected macaques.orf59 dna polymerase processivity factor of the human rhadinovirus, kaposi's sarcoma-associated herpesvirus (kshv), is required for efficient copying of the genome during virus replication. kshv orf59 is antigenic in the infected host and is used as a marker for virus activation and replication.200919922662
lymphangioma-like kaposi sarcoma: case report.kaposi sarcoma (ks) is a multifocal vascular disease with uncertain histogenesis. it is characterized by clinical and histologic polymorphism. the "lymphangioma-like" variant is very uncommon, accounting for less than 5% of all cases. we report the case of a 76-year-old woman, hiv negative, with a 4-year history of classic kaposi sarcoma treated with cryotherapy who developed new bullous lesions on her lower extremities. biopsy revealed histologic findings of lymphangioma-like ks (llks), togethe ...200919931000
kaposi's disease in a patient on adalimumab for rheumatoid arthritis. 200919945327
human herpesvirus 8 infection in hiv-1-infected and uninfected pregnant women in ethiopia.human herpes virus (hhv-8) is related to kaposi saracoma, an opportunistic infection occurring with hiv infection. little is known about the seroepidemiology of human herpesvirus 8 (hhv-8) infection among ethiopian women, even though women are a major hiv risk group in ethiopia.200919954123
is human herpesvirus-8 transmitted by transfusion?studies of human herpesvirus-8 (hhv-8) transmission through transfusion have produced contradictory results. in north america-a region with a low prevalence of hhv-8 infection-3 studies that tested specimens from linked positive-donor/negative-recipient pairs collected before the introduction of white blood cell (wbc) reduction and the extension of red blood cell (rbc) storage found no case of transmission of hhv-8 to 151 transfusion recipients who were hhv-8-seronegative before the transfusion ...201019962570
detection of human herpesvirus 8 in the skin of patients with pityriasis rosea.pityriasis rosea is an acute self-limiting dermatosis with clinical and epidemiological features that suggest viral involvement. the aim of this study was to investigate a possible association between pityriasis rosea and human herpesvirus 8 (hhv-8). lesional skin tissue was obtained from 34 kaposi's sarcoma-negative, immunocompetent patients with typical acute phase pityriasis rosea. nested polymerase chain reaction with specific primer for hhv-8 dna sequences was performed and all positive res ...200919997691
the chemokine system in cancer biology and therapy.chemokines are a key component of cancer-related inflammation. chemokines and chemokine receptors are downstream of genetic events that cause neoplastic transformation and are components of chronic inflammatory conditions, which predispose to cancer. components of the chemokine system affect in a cell autonomous or non-autonomous way multiple pathways of tumor progression, including: leukocyte recruitment and function; cellular senescence; tumor cell proliferation and survival; invasion and meta ...201020004131
human immunodeficiency virus type 1 tat accelerates kaposi sarcoma-associated herpesvirus kaposin a-mediated tumorigenesis of transformed fibroblasts in vitro as well as in nude and immunocompetent mice.kaposi sarcoma-associated herpesvirus (kshv) is necessary but not sufficient to cause kaposi sarcoma (ks). coinfection with human immunodeficiency virus type 1 (hiv-1), in the absence of antiretroviral suppressive therapy, drastically increases the risk of ks. previously, we identified that hiv-1 transactivative transcription protein (tat) was an important cofactor that activated lytic cycle replication of kshv. here, we further investigated the potential of tat to influence tumorigenesis induce ...200920019835
human herpesvirus 8 in healthy blood donors, argentina. 201020031066
the latency-associated nuclear antigen interacts with mecp2 and nucleosomes through separate domains.kaposi's sarcoma-associated herpesvirus (kshv)-infected cells express the latency-associated nuclear antigen (lana) involved in the regulation of host and viral gene expression and maintenance of the kshv latent episome. performance of these diverse functions involves a 7-amino-acid chromatin-binding motif (cbm) situated at the amino terminus of lana that is capable of binding directly to nucleosomes. lana interacts with additional chromatin components, including methyl-cpg-binding protein 2 (me ...201020032179
herpesviridae and novel inhibitors.herpesviridae comprises a large family of double-stranded dna viruses that infect both animals and humans. eight herpesviruses are known to infect humans: herpes simplex virus type-1 and -2, varicella zoster virus, human cytomegalovirus, epstein-barr virus, human herpesvirus 6 type-a and -b, human herpesvirus type-7 and -8 or kaposi's sarcoma virus. despite the fact that the past two decades have been evolutionary in the development of antiviral agents, therapeutic choices are restricted by limi ...200920032535
number of and distance between response elements in kaposi's sarcoma-associated herpesvirus orf57 promoter influence its activation by replication and transcription activator and its repression by interferon regulatory factor 7.kaposi's sarcoma-associated herpesvirus orf57 expression is highly responsive to replication and transcription activator (rta) and interferon regulatory factor 7 (irf-7). three rta response elements (rres) have been identified in the orf57 promoter. here, we show evidence of another functional rre located between nt 82003 and 82081, which can complement the loss of rta activation resulting from rre1 deletion. repeats of a recombination signal-binding protein jkappa (rbp-jkappa) site enhanced rta ...201020039088
understanding pathogenetic aspects and clinical presentation of primary effusion lymphoma through its derived cell lines.primary effusion lymphoma (pel) is a very rare subgroup of b-cell lymphomas presenting as pleural, peritoneal and pericardial neoplastic effusions in the absence of a solid tumor mass or recognizable nodal involvement. there is strong evidence that kaposi's sarcoma-associated herpesvirus (kshv) is a causal agent of pel. pel tumor cells are latently infected by kshv with consistent expression of several viral proteins and micrornas that can affect cellular proliferation, differentiation and survi ...201020051807
characterization of cytoplasmic motifs important in rhesus rhadinovirus gb processing and trafficking.rhesus monkey rhadinovirus (rrv) is highly related to kaposi's sarcoma-associated herpesvirus (kshv), a human gamma-herpesvirus etiologically-linked with several cancers. glycoprotein b (gb) homologues are encoded by all herpesviruses and play a role in virus attachment, entry, and in egress. we have found that rrv gb, like kshv gb, is cleaved at a consensus furin cleavage site and is modified by both n-linked and o-linked glycosylation. mutagenesis of three tyrosine- based trafficking motifs, a ...201020060555
characterization of the rhesus fibromatosis herpesvirus march family member rfk3.retroperitoneal fibromatosis-associated herpesvirus (rfhv) is a gamma-herpesvirus of macaques that is closely related to kaposi's sarcoma-associated herpesvirus (kshv). herein, we present characterization of the k3 gene from rfhv, a homologue of the kshv k3 and k5 genes. like the kshv proteins, kk3 and kk5, the rfk3 protein decreases cell surface mhc i levels. similar to kk5, rfk3 also modulates icam-1, but not another kk5 target, b7.2. inhibitors of dynamin or mutations in the rfk3 ring-ch e3 u ...201020060556
hhv-6, hhv-7 and hhv-8 in solid organ transplant recipients. 200920070668
hhv-6, hhv-7 and hhv-8 in solid organ transplant recipients. 200920070702
orbital involvement in castleman disease.castleman disease is a quite uncommon lymphoproliferative disorder usually occurring in the lymph nodes. rarely, castleman disease develops in an extranodal anatomic location. we report on the first biopsy-proven case of multicentric plasma cell type of castleman disease involving the orbital areas in a human herpes virus 8 (hhv-8)-unassociated/ human immunodeficiency virus (hiv)-seronegative 70-year-old man suffering from parkinson disease. the diagnosis was established on the basis of morpholo ...201020070998
epigenetic regulation of kaposi's sarcoma-associated herpesvirus latency by virus-encoded micrornas that target rta and the cellular rbl2-dnmt pathway.kaposi's sarcoma-associated herpesvirus (kshv) encodes a cluster of 12 micrornas (mirnas) that are processed from a transcript that is embedded within the major latency control region. we have generated a deletion mutation that eliminates 10 of the 12 viral mirnas from the kshv bacmid by using recombineering methods. the kshv mirna deletion mutant (bac36 deltamir) behaved similarly to wild-type (wt) bac36 in viral production, latency gene transcription, and viral dna copy number in 293 and derma ...201020071580
human herpesvirus type 8 variants circulating in europe, africa and north america in classic, endemic and epidemic kaposi's sarcoma lesions during pre-aids and aids era.human herpesvirus-8 (hhv-8) variants have been found heterogeneously distributed among human populations living in diverse geographic regions, but their differential pathogenicity in kaposi's sarcoma development remains controversial. in the present study, hhv-8 variant distribution has been analyzed in classic, iatrogenic, endemic as well as epidemic kaposi's sarcoma (ks) during pre-aids and aids period (1971-2008) in countries with different ks incidence rate. dna samples from cutaneous ks les ...201020079510
regulation of nf-kappab inhibitor ikappabalpha and viral replication by a kshv microrna.kaposi's sarcoma-associated herpesvirus (kshv) is causally linked to several acquired immune deficiency syndrome-related malignancies, including kaposi's sarcoma, primary effusion lymphoma (pel) and a subset of multicentric castleman's disease. control of viral lytic replication is essential for kshv latency, evasion of the host immune system and induction of tumours. here, we show that deletion of a 14 microrna (mirna) cluster from the kshv genome significantly enhances viral lytic replication ...201020081837
targeting cxcr4 in hiv cell-entry inhibition.cxcr4 and ccr5 constitute the two major coreceptors for hiv-1 entry into host cells. in the course of an hiv-infection, a coreceptor switch takes place in approximately half of the patients - from r5 hiv-1 (ccr5 utilizing) strains to x4 hiv-1 (cxcr4 utilizing) strains. treatment of hiv-infected individuals with cxcr4 antagonists delays the onset of aids by preventing the ccr5 to cxcr4 coreceptor switch. in addition to the endogenous cxcr4 and ccr5 ligands, other chemokines, for example the human ...200920088780
human herpesvirus 8 genomes and seroprevalence in united states blood donors.human herpesvirus 8 (hhv-8) is a gamma-herpesvirus that causes kaposi's sarcoma. the prevalence of hhv-8 genomes in us blood donors has not been systemically studied.201020088840
influence of electrostatics on the complement regulatory functions of kaposica, the complement inhibitor of kaposi's sarcoma-associated herpesvirus.kaposica, the complement regulator of kaposi's sarcoma-associated herpesvirus, inhibits complement by supporting factor i-mediated inactivation of the proteolytically activated form of c3 (c3b) and c4 (c4b) (cofactor activity [cfa]) and by accelerating the decay of classical and alternative pathway c3-convertases (decay-accelerating activity [daa]). previous data suggested that electrostatic interactions play a critical role in the binding of viral complement regulators to their targets, c3b and ...201020089702
sulfotyrosines of the kaposi's sarcoma-associated herpesvirus g protein-coupled receptor promote tumorigenesis through autocrine activation.the kaposi's sarcoma-associated herpesvirus (kshv) g protein-coupled receptor (vgpcr) is a bona fide signaling molecule that is implicated in kshv-associated malignancies. whereas vgpcr activates specific cellular signaling pathways in a chemokine-independent fashion, vgpcr binds a broad spectrum of cc and cxc chemokines, and the roles of chemokines in vgpcr tumorigenesis remain poorly understood. we report here that vgpcr is posttranslationally modified by sulfate groups at tyrosine residues wi ...201020106924
kaposi's sarcoma in a patient treated with imatinib mesylate for chronic myeloid leukemia.chronic myeloid leukemia (cml) is a myeloproliferative disorder primarily characterized by the presence of the philadelphia chromosome resulting from a reciprocal translocation between the long arms of chromosomes 9 and 22. this translocation determines a fusion gene, bcr-abl, which encodes a constitutively active protein, tyrosine kinase, resulting in decreased apoptosis, defective adhesion, and genomic instability in transformed cells. the tyrosine kinase activity and its effects represent a p ...200920110001
[research on co-infections of hiv and human herpesvirus-8 among the uygur high-risk groups in a city, xinjiang].to research the co-infections of hiv and human herpesvirus 8 (hhv8) in uygur high-risk groups of hiv infection in a city xinjiang.200920137516
substantial regional differences in human herpesvirus 8 seroprevalence in sub-saharan africa: insights on the origin of the "kaposi's sarcoma belt".equatorial africa has among the highest incidences of kaposi's sarcoma (ks) in the world, thus earning the name "ks belt." this was the case even before the hiv epidemic. to date, there is no clear evidence that hhv-8 seroprevalence is higher in this region but interpretation of the available literature is tempered by differences in serologic assays used across studies. we examined representatively sampled ambulatory adults in uganda, which is in the "ks belt," and in zimbabwe and south africa w ...201020143397
classic kaposi sarcoma in 3 unrelated turkish children born to consanguineous kindreds.infection by human herpesvirus 8 (hhv-8) in childhood is common in the mediterranean basin; however, classic kaposi sarcoma (ks) is exceedingly rare in children not infected with hiv and not receiving immunosuppression, with only 30 cases having been reported since 1960. we recently reported 2 children with autosomal and x-linked recessive primary immunodeficiencies underlying ks in a context of multiple clinical manifestations. these reports suggested that classic ks in otherwise healthy childr ...201020156905
caspase-7 cleavage of kaposi sarcoma-associated herpesvirus orf57 confers a cellular function against viral lytic gene expression.kaposi sarcoma-associated herpesvirus (kshv) orf57 is a viral early protein essential for kshv multiplication. we found that b cells derived from cavity-based b cell lymphoma with lytic kshv infection display activation of caspase-8 and cleavage of orf57 in the cytoplasm by caspase-7 at the aspartate residue at position 33 from the n terminus. caspase-7 cleavage of orf57 is prevented by pan-caspase inhibitor z-vad, caspase-3 and caspase-7 inhibitor z-devd, and caspase-7 small interfering rnas. t ...201020159985
kaposi's sarcoma associated herpes virus (kshv) induced cox-2: a key factor in latency, inflammation, angiogenesis, cell survival and invasion.kaposi's sarcoma (ks), an enigmatic endothelial cell vascular neoplasm, is characterized by the proliferation of spindle shaped endothelial cells, inflammatory cytokines (ics), growth factors (gfs) and angiogenic factors. kshv is etiologically linked to ks and expresses its latent genes in ks lesion endothelial cells. primary infection of human micro vascular endothelial cells (hmvec-d) results in the establishment of latent infection and reprogramming of host genes, and cyclooxygenase-2 (cox-2) ...201020169190
kshv-infected pel cell lines exhibit a distinct gene expression profile.we analyzed the gene expression profiles of lymphocyte-originated tumor cell lines - primary effusion lymphoma (pel) cell lines, t-cell leukemia (tcl) cell lines, burkitt lymphoma (bl) cell lines - and two sets of normal peripheral blood mononuclear cells (pbmcs) - in order to determine characteristic gene expression profiles for each of the former three groups. and we found that these cell lines showed respective typical gene expression profiles and classified into clear four groups, pel, tcl, ...201020175997
human herpesvirus 8, southern siberia. 201020202458
the kaposi's sarcoma-associated herpesvirus g protein-coupled receptor: lessons on dysregulated angiogenesis from a viral oncogene.tumor viruses can induce cell transformation by overcoming cellular defense mechanisms and promoting the ungoverned proliferation of infected cells. to this end, functionally related viral oncogenes have evolved in disparate viruses to over-ride key proliferative and survival intracellular pathways, thus assuring efficient viral replication and contributing to tumor formation. indeed, the study of viral oncogenes has been a powerful tool for disclosing fundamental insights into these basic cellu ...201020213674
human herpes virus type 8-associated kaposi sarcoma in a pediatric liver transplant recipient.çeltik c, ünüvar a, aydoğan a, gökçe s, öztürk g, güllüoğlu m, yılmaz g, türkoğlu s, anak s, sökücü s, durmaz ö. human herpes virus type 8-associated kaposi sarcoma in a pediatric liver transplant recipient.
pediatr transplantation 2010 © 2010 john wiley & sons a/s. abstract:  development of ks in pediatric liver transplant recipients is a rare entity and has dismal prognosis. latent hhv-8 infection, immunosuppression, and genetic predisposition are possible etiological factors. decreasing the d ...201020214749
human herpesvirus-8 in northwestern china: epidemiology and characterization among blood donors.human herpes virus 8 (hhv-8) is the etiologic agent associated with development of classical, aids-related, iatrogenic, and endemic kaposi's sarcoma (ks). several studies provide strong evidence that hhv-8 can be transmitted by blood transfusion. we evaluated the seroprevalence and potential risk factors of hhv-8 infection in blood donors in one region. we surveyed hhv-8 infection among 4461 blood donors in xinjiang, china, a unique endemic area for hhv-8 and ks.201020236530
dna-pk/ku complex binds to latency-associated nuclear antigen and negatively regulates kaposi's sarcoma-associated herpesvirus latent replication.during latent infection, latency-associated nuclear antigen (lana) of kaposi's sarcoma-associated herpesvirus (kshv) plays important roles in episomal persistence and replication. several host factors are associated with kshv latent replication. here, we show that the catalytic subunit of dna protein kinase (dna-pkcs), ku70, and ku86 bind the n-terminal region of lana. lana was phosphorylated by dna-pk and overexpression of ku70, but not ku86, impaired transient replication. the efficiency of tr ...201020303334
notch1 in primary effusion lymphoma: a clinicopathological study.primary effusion lymphoma is a human herpes virus 8 (hhv-8)-associated large cell lymphoma of body cavities. detailed large-scale clinicopathological studies are rarely reported, and the underlying mechanism of lymphomagenesis remains elusive. in the present report, we studied the clinicodemographic, immunophenotypic, and cytomorphological features on a cohort of 12 cases of primary effusion lymphoma. in contrast to hhv-8, which was positive in all nine cases tested (100%), hiv was found in 75% ...201020348880
making sense of antisense: seemingly noncoding rnas antisense to the master regulator of kaposi's sarcoma-associated herpesvirus lytic replication do not regulate that transcript but serve as mrnas encoding small peptides.the mammalian transcriptome is studded with putative noncoding rnas, many of which are antisense to known open reading frames (orfs). roles in the regulation of their complementary mrnas are often imputed to these antisense transcripts, but few have been experimentally examined, and such functions remain largely conjectural. kaposi's sarcoma-associated herpesvirus (kshv) encodes two transcripts that lack obvious orfs and are complementary to the gene (rta) encoding the master regulator of the la ...201020357088
mir-132 regulates antiviral innate immunity through suppression of the p300 transcriptional co-activator.micrornas are small, non-coding rnas that negatively regulate gene expression. it has been proposed that micrornas could function in the regulation of innate immunity, but this has not been demonstrated for viral infection. here we test this hypothesis using the human pathogenic virus kaposi's sarcoma-associated herpesvirus (kshv) and one of its putative natural cellular targets, primary lymphatic endothelial cells (lecs). we show that an early antiviral microrna response (6 h post-infection) in ...201020418869
microrna mir-155 inhibits bone morphogenetic protein (bmp) signaling and bmp-mediated epstein-barr virus reactivation.microrna mir-155 is expressed at elevated levels in human cancers including cancers of the lung, breast, colon, and a subset of lymphoid malignancies. in b cells, mir-155 is induced by the oncogenic latency gene expression program of the human herpesvirus epstein-barr virus (ebv). two other oncogenic herpesviruses, kaposi's sarcoma-associated herpesvirus and marek's disease virus, encode functional homologues of mir-155, suggesting a role for this microrna in the biology and pathogenesis of thes ...201020427544
kaposi's sarcoma in a psoriatic arthritis patient treated with infliximab. 201020433950
kaposi's sarcoma-associated herpesvirus orf57 protein interacts with pym to enhance translation of viral intronless mrnas.kaposi's sarcoma-associated herpesvirus (kshv) expresses numerous intronless mrnas that are unable to access splicing-dependent cellular mrna nuclear export pathways. to circumvent this problem, kshv encodes the open reading frame 57 (orf57) protein, which orchestrates the formation of an export-competent virus ribonucleoprotein particle comprising the nuclear export complex htrex, but not the exon-junction complex (ejc). interestingly, ejcs stimulate mrna translation, which raises the intriguin ...201020436455
accumulation of oxidized proteins in herpesvirus infected cells.oxidative stress gives rise to an environment that can be highly damaging to proteins, lipids, and dna. previous studies indicate that herpesvirus infections cause oxidative stress in cells and in tissues. the biological consequences of virus-induced oxidative stress have not been characterized. studies from many groups indicate that proteins which have been damaged through oxidative imbalances are either degraded by the 20s proteasome in a ubiquitin-independent fashion or form aggregates that a ...201020441790
induction, regulation, and biologic function of axl receptor tyrosine kinase in kaposi sarcoma.axl is an oncogenic receptor tyrosine kinase that plays multiple roles in tumorigenesis and metastasis of many cancers. this study is the first to demonstrate that axl is induced in kaposi sarcoma and kaposi sarcoma herpesvirus (kshv) transformed endothelial cells. conditionally, expression of one kshv latency protein vflip induces axl expression in endothelial cells. this induction can be blocked by nuclear factor-kappab inhibitor, consistent with the known vflip mechanism of action. ks cell li ...201020442363
distinct profiles of antibodies to kaposi sarcoma-associated herpesvirus antigens in patients with kaposi sarcoma, multicentric castleman disease, and primary effusion lymphoma.antibody responses against lytic and latent kaposi sarcoma (ks)-associated herpesvirus antigens were investigated in patients with ks, multicentric castleman disease (mcd), and primary effusion lymphoma. antibodies against the lytic antigen k8.1 were 5-fold higher in patients with mcd than those with ks, whereas antibodies to the sum of latent antigens v-cyclin and lana were 27-fold higher in patients with ks, compared with patients with mcd (p < 001). the sum of anti-v-cyclin and anti-lana anti ...201020443737
update on hhv-8-associated malignancies.the human herpesvirus 8 (hhv-8) is the oncogenic virus associated with kaposi's sarcoma (ks) and lymphoproliferative disorders, namely, primary effusion lymphoma and multicentric castleman's disease. ks is among the most common malignancies seen in hiv-infected patients despite the decreased incidence of ks in the era of highly active antiretroviral therapy. advances in molecular pathology reveal hhv-8 tumorigenesis is mediated through molecular mimicry wherein viral-encoded proteins can activat ...201020461118
the great escape: viral strategies to counter bst-2/tetherin.the interferon-induced bst-2 protein has the unique ability to restrict the egress of hiv-1, kaposi's sarcoma-associated herpesvirus (kshv), ebola virus, and other enveloped viruses. the observation that virions remain attached to the surface of bst-2-expressing cells led to the renaming of bst-2 as "tetherin". however, viral proteins such as hiv-1 vpu, simian immunodeficiency virus nef, and kshv k5 counteract bst-2, thereby allowing mature virions to readily escape from infected cells. since th ...201020485522
spindle cells from aids-associated kaposi's sarcoma lesions express telomerase activity that is enhanced by kaposi's sarcoma progression factors.the activity of telomerase, a ribonucleoprotein maintaining the length of chromosome ends (telomeres) to levels allowing cells to replicate indefinitely, is undetectable in normal, differentiated cells, is present at low levels in some activated cell types (including endothelial cells) and it is highly expressed by tumor cells. kaposi's sarcoma (ks), the most frequent tumor in acquired immune deficiency syndrome (aids) patients (aids-ks), arises as a disorder of new blood vessel formation (angio ...201020514465
comparative study of murid gammaherpesvirus 4 infection in mice and in a natural host, bank voles.gammaherpesviruses are archetypal pathogenic persistent viruses. the known human gammaherpesviruses (epstein-barr virus and kaposi's sarcoma-associated herpesvirus) are host-specific and therefore lack a convenient in vivo infection model. this makes related animal gammaherpesviruses an important source of information. infection by murid herpesvirus 4 (muhv-4), a virus originally isolated from bank voles (myodes glareolus), was studied here. muhv-4 infection of inbred laboratory mouse strains (m ...201020538905
prevalence of human herpesvirus 8 and hepatitis c virus in a rural community with a high risk for blood-borne infections in central china.illegal blood donation in the past decade has caused human immunodeficiency virus (hiv) outbreaks in some rural areas in china. other hiv-associated virus infections, such as those caused by human herpesvirus 8 (hhv8), in such areas are still not well defined. in order to explore hhv8 and hepatitis c virus (hcv) seroprevalence and potential risk factors in such areas, a cross-sectional study with 305 hiv-positive and 315 hiv-negative subjects recruited from a rural county in shanxi province was ...201120545961
small rna profiling reveals antisense transcription throughout the kshv genome and novel small rnas.kaposi's sarcoma-associated herpesvirus (kshv) is a human tumor virus that encodes 12 precursor micrornas (pre-mirnas) that give rise to 17 different known approximately 22-nucleotide (nt) effector mirnas. like all herpesviruses, kshv has two modes of infection: (1) a latent mode whereby only a subset of viral genes are expressed and (2) a lytic mode during which the full remaining viral genes are expressed. to date, kshv mirnas have been mostly identified via analysis of cells that are undergoi ...201020566670
human herpes virus type 8 seroprevalence in pregnant women in geneva, switzerland.because of increasing migration, european countries are facing new pathogens and diseases, such as human herpes virus-8 (hhv-8). we assessed the prevalence of hhv-8 using a new elisa test in 140 pregnant women delivering in geneva (switzerland). the prevalence of hhv-8 was 7.9% globally and up to 33.3% in the african subpopulation. seropositive women were more frequently older (≥32 years old) than seronegative ones: 81.8% vs. 43%; p = 0.023, respectively. in conclusion, hhv-8 infection is presen ...201120569167
cidofovir-loaded liposomes: an intro-study using bcbl-1 cell line as a model for primary effusion lymphoma.cidofovir (hpmpc) was recently reported to exert a valuable antineoplastic activity against primary effusion lymphoma (pel), a b-cell neoplasm associated with human herpesvirus-8 (hhv-8) infection. in this study, we developed and characterized liposomes encapsulating hpmpc to increase drug efficacy reducing the administered dose and the related toxicity, which actually hamper its clinical therapeutic use in patients affected with pel. the liposomes, obtained using different formulations of neutr ...201020600876
patterns of antibodies against latent and lytic antigens of human herpesvirus 8 in an endemic population and patients with kaposi's sarcoma in mozambique.the patterns of antibodies against latent and lytic antigens of human herpesvirus 8 (hhv-8) were assessed using immunofluorescence assays of samples from 155 persons seropositive for hhv-8 seen at public health centers and 24 patients with kaposi's sarcoma (ks) from mozambique. of the 155 persons without ks, 48 (31%) had antibodies against latent antigens only, 29 (18.7%) had antibodies against lytic antigens only, and 78 (50.3%) had antibodies against both types of antigen. the hhv-8 antibody t ...201020648612
bub1 and cenp-f can contribute to kaposi's sarcoma-associated herpesvirus genome persistence by targeting lana to kinetochores.the latency-associated nuclear antigen (lana) encoded by kaposi's sarcoma-associated herpesvirus (kshv) is critical for segregation of viral episomes to progeny nuclei and allows for maintenance of the viral genome in newly divided daughter cells. lana binds to kshv terminal repeat (tr) dna and simultaneously associates with chromatin-bound cellular proteins. this process tethers the viral episomes to host chromosomes. however, the mechanism of tethering is complex and involves multiple protein- ...201020660191
characterization of entry and infection of monocytic thp-1 cells by kaposi's sarcoma associated herpesvirus (kshv): role of heparan sulfate, dc-sign, integrins and signaling.kshv effectively binds, enters and establishes infection in thp-1 cells with initial concurrent expression of latent orf73 and lytic orf50 genes and subsequent persistence of orf73. kshv genome persisted for 30 days and lytic cycle could be activated. kshv utilized heparan sulfate for binding to thp-1 cells and primary monocytes. blocking dc-sign did not inhibit kshv binding; however, virus entry in thp-1 cells and in primary monocytes was reduced. in addition to the previously identified integr ...201020674951
convergence of kaposi's sarcoma-associated herpesvirus reactivation with epstein-barr virus latency and cellular growth mediated by the notch signaling pathway in coinfected cells.kaposi's sarcoma-associated herpesvirus (kshv) is the etiologic agent of primary effusion lymphoma (pel). all pel cell lines are infected with kshv, and 70% are coinfected with epstein-barr virus (ebv). kshv reactivation from latency requires promoter-specific transactivation by the kshv rta protein through interactions with rbp-jk (csl), the cellular dna-binding component of the notch signal transduction pathway. ebv transformation of primary b cells requires ebv nuclear antigen 2 (ebna-2) to i ...201020686042
the human cytomegalovirus microrna mir-ul112 acts synergistically with a cellular microrna to escape immune elimination.although approximately 200 viral micrornas are known, only very few share similar targets with their host's micrornas. a notable example of this is the stress-induced ligand micb, which is targeted by several distinct viral and cellular micrornas. through the investigation of the microrna-mediated immune-evasion strategies of herpesviruses, we initially identified two new cellular micrornas that targeted micb and were expressed differently both in healthy tissues and during melanocyte transforma ...201020694010
endogenous cd317/tetherin limits replication of hiv-1 and murine leukemia virus in rodent cells and is resistant to antagonists from primate viruses.human cd317 (bst-2/tetherin) is an intrinsic immunity factor that blocks the release of retroviruses, filoviruses, herpesviruses, and arenaviruses. it is unclear whether cd317 expressed endogenously in rodent cells has the capacity to interfere with the replication of the retroviral rodent pathogen murine leukemia virus (mlv) or, in the context of small-animal model development, contributes to the well-established late-phase restriction of human immunodeficiency virus type 1 (hiv-1). here, we sh ...201020702620
monofunctional and polyfunctional cd8+ t cell responses to human herpesvirus 8 lytic and latency proteins.human herpesvirus 8 (hhv-8) is the etiological agent of kaposi's sarcoma, primary effusion lymphoma, and multicentric castleman's disease. it is postulated that cd8(+) t cell responses play an important role in controlling hhv-8 infection and preventing development of disease. in this study, we investigated monofunctional and polyfunctional cd8(+) t cell responses to hhv-8 lytic proteins gb (glycoprotein b) and k8.1 and latency proteins lana-1 (latency-associated nuclear antigen-1) and k12. on t ...201020719985
rhesus rhadinovirus infection of rhesus fibroblasts occurs through clathrin-mediated endocytosis.rhesus rhadinovirus (rrv) is a gammaherpesvirus closely related to kaposi's sarcoma-associated herpesvirus (kshv), an oncogenic virus linked to the development of kaposi's sarcoma and several other lymphoproliferative diseases, including primary effusion lymphoma and multicentric castleman's disease. rrv naturally infects rhesus macaques and induces lymphoproliferative diseases under experimental conditions, making it an excellent model for the study of kshv. unlike kshv, which grows poorly in c ...201020826690
requirement of uap56, urh49, rbm15, and ott3 in the expression of kaposi sarcoma-associated herpesvirus orf57.transport of mrna from the nucleus to the cytoplasm is mediated by cellular rna export factors. in this report, we examined how rna export factors uap56 and urh49, and rna export cofactors rbm15 and ott3, function in modulating kshv orf57 expression. we found that knockdown of each factor by rnai led to decreased orf57 expression. specifically, reduced expression of either uap56 or rbm15 led to nuclear export deficiency of orf57 rna. in the context of the kshv genome, the near absence of uap56 o ...201020828777
nf-κb as a target for oncogenic viruses.nf-κb is a pivotal transcription factor that controls cell survival and proliferation in diverse physiological processes. the activity of nf-κb is tightly controlled through its cytoplasmic sequestration by specific inhibitors, iκbs. various cellular stimuli induce the activation of an iκb kinase, which phosphorylates iκbs and triggers their proteasomal degradation, causing nuclear translocation of activated nf-κb. under normal conditions, the activation of nf-κb occurs transiently, thus ensurin ...201120845110
micrornas encoded by kaposi's sarcoma-associated herpesvirus regulate viral life cycle.kaposi's sarcoma-associated herpesvirus (kshv) is linked with kaposi's sarcoma and lymphomas. the pathogenesis of kshv depends on the balance between two phases of the viral cycle: latency and lytic replication. in this study, we report that kshv-encoded micrornas (mirnas) function as regulators by maintaining viral latency and inhibiting viral lytic replication. mirnas are short, noncoding, small rnas that post-transcriptionally regulate the expression of messenger rnas. of the 12 viral mirnas ...201020847741
immune evasion by kaposi's sarcoma-associated herpesvirus.persistent viral infections are often associated with serious diseases, primarily by altering functions of the host immune system. the hallmark of kaposi's sarcoma-associated herpesvirus (kshv) infection is the establishment of a life-long persistent infection, which leads to several clinical, epidemiological and infectious diseases, such as kaposi's sarcoma, a plasmablastic variant of multicentric castleman's disease, and primary effusion lymphoma. to sustain an efficient life-long persistency, ...201020860481
identifying dysregulated genes induced by kaposi's sarcoma-associated herpesvirus (kshv).currently ks is the most predominant hiv/aids related malignancy in southern africa and hence the world. it is characterized as an angioproliferative tumor of vascular endothelial cells and produces rare b cell lymphoproliferative diseases in the form of pleural effusion lymphomas (pel) and some forms of multicentric castleman's disease. only 1-5% of cells in ks lesions actively support lytic replication of kaposi's sarcoma-associated herpesvirus (kshv), the etiological agent associated with ks, ...201020864930
whole-exome sequencing-based discovery of stim1 deficiency in a child with fatal classic kaposi sarcoma.classic kaposi sarcoma (ks) is exceedingly rare in children from the mediterranean basin, despite the high prevalence of human herpesvirus-8 (hhv-8) infection in this region. we hypothesized that rare single-gene inborn errors of immunity to hhv-8 may underlie classic ks in childhood. we investigated a child with no other unusually severe infectious or tumoral phenotype who died from disseminated ks at two years of age. whole-exome sequencing in the patient revealed a homozygous splice-site muta ...201020876309
mirnas in the pathogenesis of oncogenic human viruses.tumor viruses are a class of pathogens with well established roles in the development of malignant diseases. numerous bodies of work have highlighted mirnas (micrornas) as critical regulators of tumor pathways and it is clear that the dysregulation of cellular mirna expression can promote tumor formation. tumor viruses encode their own mirnas and/or manipulate the expression of cellular mirnas to modulate their host cell environment, thereby facilitating their respective infection cycles. the mo ...201020943311
detection of human herpesvirus 6 dna but not human herpesvirus 7 or 8 dna in atherosclerotic and nonatherosclerotic vascular tissues.various viral infections are thought to play a role in the development of atherosclerosis. a number of studies suggest that certain viruses from the herpesviridae family in particular may lead to atherosclerosis.201020961841
pemphigus vulgaris and herpesviruses: is there any relationship?pemphigus is an autoimmune disorder, which results from interaction of exogenous and endogenous factors. one of these environmental factors is viral infections particularly, herpesviruses. we aimed to detect the presence of hsv 1 and 2 (herpes simplex virus) and hhv8 (human herpesvirus 8) in our patients who were suffering from pemphigus vulgaris.201021038546
getting the message direct manipulation of host mrna accumulation during gammaherpesvirus lytic infection.the gammaherpesvirinae subfamily of herpesviruses comprises lymphotropic viruses, including the oncogenic human pathogens epstein-barr virus and kaposi's sarcoma-associated herpesvirus. during lytic infection, gammaherpesviruses manipulate host gene expression to optimize the cellular environment for viral replication and to evade the immune response. additionally, although a lytically infected cell will itself be killed in the process of viral replication, lytic infection can contribute to path ...201021040830
new drug targets in kaposi sarcoma.kaposi sarcoma (ks) occurs as a result of kaposi sarcoma-associated herpesvirus (kshv) infection, typically in the context of an immunodeficient state such as coinfection with hiv or transplantation. systemic treatment of ks has traditionally involved one of several chemotherapeutic agents either in combination or as single agents, which typically provides reasonable response rates and short-term control. however, recurrence of ks is common and progression-free intervals are short. for these rea ...201021043836
the lytic activation of kshv during keratinocyte differentiation is dependent upon a suprabasal position, the loss of integrin engagement, and calcium, but not the interaction of cadherins.we previously found that kshv (hhv-8) lytic activation occurs during differentiation of oral keratinocytes in organotypic raft cultures. to further investigate the spatial and temporal aspects of kshv lytic activation and the roles of integrins, cadherins, and calcium, we used rkshv.219-infected primary oral keratinocytes in submerged, suspension, and direct suprabasal plating, models of differentiation. we found that early keratinocyte differentiation did not activate lytic kshv in cells attach ...201021084105
tumor viruses and cancer biology: modulating signaling pathways for therapeutic intervention.tumor viruses have provided relatively simple genetic systems, which can be manipulated for understanding the molecular mechanisms of the cellular transformation process. a growing body of information in the tumor virology field provides several prospects for rationally targeted therapies. however, further research is needed to better understand the multiple mechanisms utilized by these viruses in cancer progression in order to develop therapeutic strategies. initially viruses were believed to b ...201021084867
risk factors influencing antibody responses to kaposi's sarcoma-associated herpesvirus latent and lytic antigens in patients under antiretroviral therapy.kaposi's sarcoma-associated herpesvirus (kshv) seropositivity and lytic antibody titer are predictors for kaposi's sarcoma.201121084997
hla polymorphisms and detection of kaposi sarcoma-associated herpesvirus dna in saliva and peripheral blood among children and their mothers in the uganda sickle cell anemia kshv study.abstract: kaposi sarcoma-associated herpesvirus (kshv, also called human herpesvirus 8 or hhv8) is a γ-2 herpesvirus that causes kaposi sarcoma. kshv seroprevalence rates vary geographically with variable rates recorded in different sub sahara african countries, suggesting that effects of genetic and/or environmental factors may influence the risk of infection. one study conducted in south africa, where kshv seroprevalence is relatively low, found that carriage of human leukocyte antigen (hla) a ...201021087485
reverse transfected cell microarrays in infectious disease research.several human pathogenic viruses encode large genomes with often more than 100 genes. viral pathogenicity is determined by carefully orchestrated co-operative activities of several different viral genes which trigger the phenotypic functions of the infected cells. systematic analyses of these complex interactions require high-throughput transfection technology. here we have provided a laboratory manual for the reverse transfected cell microarray (rtcm; alternative name: cell chip) as a high-thro ...201121104058
poly(a) tail recognition by a viral rna element through assembly of a triple helix.kaposi's sarcoma-associated herpesvirus produces a highly abundant, nuclear noncoding rna, polyadenylated nuclear (pan) rna, which contains an element that prevents its decay. the 79-nucleotide expression and nuclear retention element (ene) was proposed to adopt a secondary structure like that of a box h/aca small nucleolar rna (snorna), with a u-rich internal loop that hybridizes to and protects the pan rna poly(a) tail. the crystal structure of a complex between the 40-nucleotide ene core and ...201021109672
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