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hiv-associated kaposi sarcoma and related diseases.: the search for the etiologic agent for kaposi sarcoma led to the discovery of kaposi sarcoma-associated herpesvirus (kshv) in 1994. kshv, also called human herpesvirus-8, has since been shown to be the etiologic agent for several other tumors and diseases, including primary effusion lymphoma (pel), an extracavitary variant of pel, kshv-associated diffuse large b-cell lymphoma, a form of multicentric castleman disease, and kshv inflammatory cytokine syndrome. kshv encodes several genes that int ...201728609402
high seroprevalence of human herpesvirus 8 infection in hiv-positive homosexual men in jiangsu province, china.hiv-infected homosexual men are more frequently diagnosed with kaposi's sarcoma. with the increase of hiv-infected homosexual men in china, we urgently need to know the ks-related human herpesvirus (kshv/hhv-8) seroprevalence in this population. to investigate the hhv-8 prevalence among hiv-positive homosexual men, we recruited 183 patients naive of antiretroviral therapy (art) whose blood samples present hiv-antibody positive confirmed by western blot.201728606034
an easily transfectable cell line that produces an infectious reporter virus for routine and robust quantitation of kaposi's sarcoma-associated herpesvirus reactivation.reactivation of kaposi's sarcoma-associated herpesvirus (khsv; also known as human herpesvirus (hhv)-8) from latency is associated with progression to disease. the primary experimental models for studying kshv reactivation are b lymphocyte cell lines derived from patients with primary effusion lymphoma (pel). pel models have remained essential tools for understanding molecular details of latency and reactivation, yet they have shortcomings. in particular, pel cells are difficult to transfect wit ...201728602767
functional dissection of human targets for kshv-encoded mirnas using network analysis.kaposi's sarcoma-associated herpesvirus (kshv) is the etiological agent of kaposi's sarcoma, primary effusion lymphoma and multicentric castleman's disease, etc. in this study, we firstly systematically constructed the kshv-encoded mirna-regulated co-expressed protein-protein interaction network (ceppin), which display the biological knowledge regarding the mechanism of mirna-regulated kshv pathogenesis. then, we investigated the topological parameters for the proteins in ceppin, especially for ...201728600495
kaposi's sarcoma-associated herpesvirus utilizes and manipulates rna n(6)-adenosine methylation to promote lytic replication.n(6)-adenosine methylation (m(6)a) is the most common posttranscriptional rna modification in mammalian cells. we found that most transcripts encoded by the kaposi's sarcoma-associated herpesvirus (kshv) genome undergo m(6)a modification. the levels of m(6)a-modified mrnas increased substantially upon stimulation for lytic replication. the blockage of m(6)a inhibited splicing of the pre-mrna encoding the replication transcription activator (rta), a key kshv lytic switch protein, and halted viral ...201728592530
guanylate-binding protein 1 inhibits nuclear delivery of kaposi's sarcoma-associated herpesvirus virions by disrupting formation of actin filament.kaposi's sarcoma-associated herpesvirus (kshv) is a typical gammaherpesvirus that establishes persistent lifelong infection in host cells. in order to establish successful infection, kshv has evolved numerous immune evasion strategies to bypass or hijack the host immune system. however, host cells still produce immune cytokines abundantly during primary kshv infection. whether the immune effectors produced are able to inhibit viral infection and how kshv successfully conquers these immune effect ...201728592529
case report of a primary effusion lymphoma successfully treated with oral valganciclovir after failing chemotherapy.primary effusion lymphoma is a rare non-hodgkin lymphoma that presents with pleural effusions and lacking of tumour mass. it is universally associated with human herpesvirus 8 (hhv8) and is more frequent among immunosuppressed patients. there is no standard treatment, chemotherapy and anti-hiv therapy have been used with poor results, but there is still no strong evidence supporting the use of valganciclovir. we present the case of a hiv positive man that presented with pleural effusion compatib ...201728580733
seroprevalence of antibodies against kaposi's sarcoma-associated herpesvirus among hiv-negative people in china.little information on the prevalence of kaposi's sarcoma associated herpesvirus (kshv) among hiv-negative individuals is available from asia.201728572838
comparison of kaposi sarcoma risk in hiv-positive adults across five continents: a multiregional multicohort study.we compared kaposi sarcoma (ks) risk in adults who initiated antiretroviral therapy (art) across the asia-pacific, south africa, europe, latin, and north america.201728531260
virus-like vesicles of kaposi's sarcoma-associated herpesvirus activate lytic replication by triggering differentiation signaling.virus-like vesicles (vlvs) are membrane-enclosed vesicles that resemble native enveloped viruses in organization but lack the viral capsid and genome. during the productive infection of tumor-associated gammaherpesviruses, both virions and vlvs are produced and are released into the extracellular space. however, studies of gammaherpesvirus-associated vlvs have been largely restricted by the technical difficulty of separating vlvs from mature virions. here we report a strategy of selectively isol ...201728515293
human herpesvirus 8-related diseases: histopathologic diagnosis and disease mechanisms.the emergence of hiv/aids more than three decades ago led to an increased incidence of diseases caused by hhv8 co-infection, particularly kaposi sarcoma, primary effusion lymphoma, and multicentric castleman disease. over time, the development of highly effective aids therapies has resulted in a decreased incidence of hhv8-associated entities, which are now more commonly found in patients with undiagnosed and/or untreated aids. due to their rarity, some of these diseases may be difficult to reco ...201728502522
multicentric castleman disease of hyaline vascular variant presenting with unusual systemic manifestations: a case report.castleman disease is a rare lymphoproliferative disorder presenting with localized or disseminated lymphadenopathy and systemic manifestations. it can be categorized in numerous ways, such as unicentric versus multicentric, histopathological variants (hyaline-vascular, plasma cell, and mixed), or subtypes based on causative viral infections (human immunodeficiency virus, human herpesvirus-8, or kaposi sarcoma herpesvirus). presentation ranges from asymptomatic to symptoms involving multiple orga ...201728501028
successful treatment of kaposi sarcoma-associated herpesvirus inflammatory cytokine syndrome after kidney-liver transplant: correlations with the human herpesvirus 8 mirnome and specific t cell response.after transplant, patient infection with human herpesvirus 8 (hhv-8) and kaposi sarcoma-associated herpesvirus (kshv) is known to cause aggressive tumors and severe nonneoplastic complications. these latter syndromes are driven by hhv-8/kshv lytic reactivations and related hyperinflammatory host responses typically characterized by high viral loads, elevated levels of cytokines and other inflammation biomarkers, cytopenia, organ failure, high fever, and worsening conditions (with no evidence of ...201728489271
reactivation and lytic replication of kaposi's sarcoma-associated herpesvirus: an update.the life cycle of kaposi's sarcoma-associated herpesvirus (kshv) consists of two phases, latent and lytic. the virus establishes latency as a strategy for avoiding host immune surveillance and fusing symbiotically with the host for lifetime persistent infection. however, latency can be disrupted and kshv is reactivated for entry into the lytic replication. viral lytic replication is crucial for efficient dissemination from its long-term reservoir to the sites of disease and for the spread of the ...201728473805
nlrx1 negatively modulates type i ifn to facilitate kshv reactivation from latency.kaposi's sarcoma-associated herpesvirus (kshv) is a herpesvirus that is linked to kaposi's sarcoma (ks), primary effusion lymphoma (pel) and multicentric castleman's disease (mcd). kshv establishes persistent latent infection in the human host. kshv undergoes periods of spontaneous reactivation where it can enter the lytic replication phase of its lifecycle. during kshv reactivation, host innate immune responses are activated to restrict viral replication. here, we report that nlrx1, a negative ...201728459883
ribonucleotide reductase represents a novel therapeutic target in primary effusion lymphoma.primary effusion lymphoma (pel) is a highly aggressive b-cell malignancy that is closely associated with one of oncogenic viruses infection, kaposi's sarcoma-associated herpesvirus. pel prognosis is poor and patients barely survive >6 months even following active chemotherapy interventions. there is therefore an urgent need to discover more effective targets for pel management. we recently found that the ribonucleotide reductase (rr) subunit m2 is potentially regulated by the key oncogenic hepat ...201728459467
incorporation of the kaposi's sarcoma-associated herpesvirus capsid vertex-specific component (cvsc) into self-assembled capsids.self-assembly of herpesvirus capsids can be accomplished in heterologous expression systems provided all six capsid proteins are present. we have demonstrated the assembly of icosahedral kaposi's sarcoma-associated herpesvirus (kshv) capsids in insect cells using the baculovirus expression system. using this self-assembly system we investigated whether we could add additional capsid associated proteins and determine their incorporation into the assembled capsid. we chose the capsid vertex-specif ...201728456575
rhadinoviral interferon regulatory factor homologues.kaposi's sarcoma-associated herpesvirus (kshv), or human herpesvirus 8 (hhv8) is a gammaherpesvirus and the etiological agent of kaposi's sarcoma, primary effusion lymphoma and multicentric castleman disease. the kshv genome contains genes for a unique group of proteins with homology to cellular interferon regulatory factors, termed viral interferon regulatory factors (virfs). this review will give an overview over the oncogenic, antiapoptotic and immunomodulatory characteristics of kshv and rel ...201728455950
kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen: replicating and shielding viral dna during viral persistence.kaposi's sarcoma herpesvirus (kshv) establishes lifelong latency. the viral latency-associated nuclear antigen (lana) promotes viral persistence by tethering the viral genome to cellular chromosomes and by participating in latent dna replication. recently, the structure of the lana c-terminal dna binding domain was solved and new cytoplasmic variants of lana were discovered. we discuss how these findings contribute to our current view of lana structure and assembly and of its role during viral p ...201728446671
kaposi sarcoma inflammatory cytokine syndrome (kics): a rare but potentially treatable condition.kaposi sarcoma inflammatory cytokine syndrome (kics) is a newly-described condition affecting individuals who are hiv-positive and are infected with human herpesvirus 8 (hhv-8). this is a syndrome that in some ways mimics severe sepsis with associated acute respiratory distress syndrome, possibly requiring a ventilator and vasopressor support. however, unlike severe sepsis, antibiotics provide no benefit. management of kics has not been fully elucidated because of its high mortality rate. howeve ...201728424322
molecular mechanisms of activating c-met in kshv+ primary effusion lymphoma.the oncogenic kaposi's sarcoma-associated herpesvirus (kshv) is a principal causative agent of primary effusion lymphoma (pel), which is mostly seen in immunosuppressed patients. pel is a rapidly progressing malignancy with a median survival time of approximately 6 months even under the conventional chemotherapy. we recently report that the hepatocyte growth factor (hgf)/c-met pathway is highly activated in pel cells and represents a promising therapeutic target (blood. 2015;126(26):2821-31). ho ...201728407694
sirt1 and ampk pathways are essential for the proliferation and survival of primary effusion lymphoma cells.primary effusion lymphoma (pel) is a rare and aggressive b-cell lymphoma with a dismal prognosis caused by infection of kaposi's sarcoma-associated herpesvirus. despite the findings that numerous viral genes and cellular pathways are essential for the proliferation and survival of pel cells, there is currently no effective therapeutic treatment for pel. here, we report that the metabolic sensor sirt1 is functionally required for sustaining the proliferation and survival of pel cells. knockdown o ...201728393364
kshv-encoded viral interferon regulatory factor 4 (virf4) interacts with irf7 and inhibits interferon alpha production.before an infection can be completely established, the host immediately turns on the innate immune system through activating the interferon (ifn)-mediated antiviral pathway. kaposi's sarcoma-associated herpesvirus (kshv) utilizes a unique antagonistic mechanism of type i ifn-mediated host antiviral immunity by incorporating four viral interferon regulatory factors (virf1-4). herein, we characterized novel immune evasion strategies of virf4 to inhibit the irf7-mediated ifn-α production. kshv virf ...201728342865
quantitative analysis of the kshv transcriptome following primary infection of blood and lymphatic endothelial cells.the transcriptome of the kaposi's sarcoma-associated herpesvirus (kshv/hhv8) after primary latent infection of human blood (bec), lymphatic (lec) and immortalized (time) endothelial cells was analyzed using rnaseq, and compared to long-term latency in bcbl-1 lymphoma cells. naturally expressed transcripts were obtained without artificial induction, and a comprehensive annotation of the kshv genome was determined. a set of unique coding sequence (ucds) features and a process to resolve overlappin ...201728335496
kaposi's sarcoma-associated herpesvirus hijacks rna polymerase ii to create a viral transcriptional factory.locally concentrated nuclear factors ensure efficient binding to dna templates, facilitating rna polymerase ii recruitment and frequent reutilization of stable preinitiation complexes. we have uncovered a mechanism for effective viral transcription by focal assembly of rna polymerase ii around kaposi's sarcoma-associated herpesvirus (kshv) genomes in the host cell nucleus. using immunofluorescence labeling of latent nuclear antigen (lana) protein, together with fluorescence in situ rna hybridiza ...201728331082
modulation of oncogenic signaling networks by kaposi's sarcoma-associated herpesvirus.kaposi's sarcoma-associated herpesvirus (kshv) is the etiological agent of three human malignancies: kaposi's sarcoma, primary effusion lymphoma, and multicentric castleman's disease. to persist and replicate within host cells, kshv encodes proteins that modulate different signaling pathways. manipulation of cell survival and proliferative networks by kshv can promote the development of kshv-associated malignancies. in this review, we discuss recent updates on kshv pathogenesis and the viral lif ...201728284028
kshv micrornas: tricks of the devil.kaposi's sarcoma-associated herpesvirus (kshv) is the etiologic agent of kaposi's sarcoma (ks), a vascular tumor frequently found in immunodeficient individuals. kshv encodes 12 pre-micrornas (pre-mirnas), which are processed into 25 mature micrornas (mirnas). kshv mirnas maintain kshv latency, enhance angiogenesis and dissemination of the infected cells, and interfere with the host immune system by regulating viral and cellular gene expression, ultimately contributing to ks development. in this ...201728259385
integrated systems biology analysis of kshv latent infection reveals viral induction and reliance on peroxisome mediated lipid metabolism.kaposi's sarcoma associated herpesvirus (kshv), an oncogenic, human gamma-herpesvirus, is the etiological agent of kaposi's sarcoma the most common tumor of aids patients world-wide. kshv is predominantly latent in the main ks tumor cell, the spindle cell, a cell of endothelial origin. kshv modulates numerous host cell-signaling pathways to activate endothelial cells including major metabolic pathways involved in lipid metabolism. to identify the underlying cellular mechanisms of kshv alteration ...201728257516
sumo modification of a heterochromatin histone demethylase jmjd2a enables viral gene transactivation and viral replication.small ubiquitin-like modifier (sumo) modification of chromatin has profound effects on transcription regulation. by using kaposi's sarcoma associated herpesvirus (kshv) as a model, we recently demonstrated that epigenetic modification of viral chromatin by sumo-2/3 is involved in regulating gene expression and viral reactivation. however, how this modification orchestrates transcription reprogramming through targeting histone modifying enzymes remains largely unknown. here we show that jmjd2a, t ...201728212444
simultaneous detection of dual nucleic acids using a sers-based lateral flow assay biosensor.a new class of surface-enhanced raman scattering (sers)-based lateral flow assay (lfa) biosensor has been developed for the simultaneous detection of dual dna markers. the lfa strip in this sensor was composed of two test lines and one control line. sers nano tags labeled with detection dna probes were used for quantitative evaluation of dual dna markers with high sensitivity. target dna, associated with kaposi's sarcoma-associated herpesvirus (kshv) and bacillary angiomatosis (ba), were tested ...201728194991
methylseleninic acid and sodium selenite induce severe er stress and subsequent apoptosis through upr activation in pel cells.selenium compounds such as methylseleninic acid (msa) and sodium selenite (ss) have been widely evaluated as potential anti-cancer agents in the clinical setting. primary effusion lymphoma (pel) is a non-hodgkin's b-cell lymphoma, associated with immunosuppressed individuals, such as post-transplant or aids patients. kaposi's sarcoma-associated herpesvirus (kshv) is the causative agent of pel and kaposi's sarcoma. here, we found that msa and ss markedly inhibited the growth of pel cells compared ...201728161410
relapse of hhv8-positive multicentric castleman disease following rituximab-based therapy in hiv-positive patients.successful treatment of hiv-associated multicentric castleman disease (hiv+mcd) with rituximab-based approaches has dramatically improved survival and reduced the risk of human herpesvirus 8 (hhv8)-associated lymphoma. longer term outcomes including relapse rates have not been described and are important to establish the potential role of maintenance therapy. a prospective cohort of 84 patients with biopsy-proven hiv+mcd were treated with risk-stratified rituximab-based therapy. four patients (5 ...201728143881
epigenetic landscape of kaposi's sarcoma-associated herpesvirus genome in classic kaposi's sarcoma tissues.kaposi's sarcoma-associated herpesvirus (kshv) is etiologically related to kaposi's sarcoma (ks), primary effusion lymphoma (pel) and multicentric castleman's disease (mcd). it typically displays two different phases in its life cycle, the default latency and occasional lytic replication. the epigenetic modifications are thought to determine the fate of kshv infection. previous studies elegantly depicted epigenetic landscape of latent viral genome in in vitro cell culture systems. however, the p ...201728118409
bet-inhibitors disrupt rad21-dependent conformational control of kshv latency.kaposi's sarcoma-associated herpesvirus (kshv) establishes stable latent infection in b-lymphocytes and pleural effusion lymphomas (pels). during latency, the viral genome persists as an epigenetically constrained episome with restricted gene expression programs. to identify epigenetic regulators of kshv latency, we screened a focused small molecule library containing known inhibitors of epigenetic factors. we identified jq1, a bromodomain and extended terminal (bet) protein inhibitor, as a pote ...201728107481
viral micrornas target a gene network, inhibit stat activation, and suppress interferon responses.kaposi's sarcoma-associated herpesvirus (kshv) encodes 12 pre-micrornas during latency that are processed to yield ~25 mature micrornas (mirnas). we were interested in identifying cellular networks that were targeted by kshv-mirnas and employed network building strategies using validated kshv mirna targets. here, we report the identification of a gene network centering on the transcription factor- signal transducer and activator of transcription 3 (stat3) that is targeted by kshv mirnas. kshv mi ...201728102325
stable persistence of the yeast plasmid by hitchhiking on chromosomes during vegetative and germ-line divisions of host cells.the chromosome-like stability of the saccharomyces cerevisiae plasmid 2 micron circle likely stems from its ability to tether to chromosomes and segregate by a hitchhiking mechanism. the plasmid partitioning system, responsible for chromosome-coupled segregation, is comprised of 2 plasmid coded proteins rep1 and rep2 and a partitioning locus stb. the evidence for the hitchhiking model for mitotic plasmid segregation, although compelling, is almost entirely circumstantial. direct tests for plasmi ...201726442178
lessons learned from in vivo studies of a viral noncoding rna.despite increasing interest in the biology of noncoding rnas (ncrnas), few functions have been uncovered for viral ncrnas in vivo. in their recent article in msphere, feldman and colleagues [e. r. feldman et al., msphere 1(2):e00105-15, 2016, doi:10.1128/msphere.00105-15] demonstrate a highly specific activity of a gammaherpesviral ncrna in viral dissemination and establishment of latent infection. their work highlights several interesting features that should be informative to future studies of ...201727301787
regulation of the viral life cycle by murine gammaherpesvirus 68 micrornas.γ-herpesviruses (γhv) such as epstein-barr virus and kaposi's sarcoma-associated herpesvirus are important human pathogens involved in lymphoproliferation and tumorigenesis. murine gammaherpesvirus 68 (mhv-68, γhv-68) is an effective model for the study of γhv pathogenesis and host-virus interaction because it is closely related to human γhv. similarly to human γhv, mhv-68 encodes 15 micrornas (mirnas). although their functions remain unknown, they are thought to regulate the viral life cycle or ...201727837274
constitutive activation of t cells by γ2-herpesviral gpcr through the interaction with cellular cxcr4.members of the herpesviral family use multiple strategies to hijack infected host cells and exploit cellular signaling for their pathogenesis and latent infection. among the most intriguing weapons in the arsenal of pathogenic herpesviruses are the constitutively active virally-encoded g protein-coupled receptors (vgpcrs). even though vgpcrs contribute to viral pathogenesis such as immune evasion and proliferative disorders, the molecular details of how vgpcrs continuously activate cellular sign ...201727751885
intravascular large b-cell lymphoma: a difficult diagnostic challenge.case presentation. a 69-year-old hispanic male, with a past history of diabetes and coronary disease, was admitted for fever, diarrhea, and confusion of 4 weeks duration. physical examination showed a disoriented patient with multiple ecchymoses, possible ascites, and bilateral scrotal swelling. hemoglobin was 6.7, prothrombin time (pt) 21.4 seconds with international normalized ratio 2.1, partial thromboplastin time (ptt) 55.6 seconds, fibrin split 10 µg/l, and lactate dehydrogenase (ldh) 1231 ...201726425595
role of infectious agents in cutaneous t-cell lymphoma: facts and controversies.the etiology of cutaneous t-cell lymphoma (ctcl) remains unknown, with potential infectious causes having been explored. this contribution evaluates the evidence suggesting an infectious etiology and pathogenesis of the disease, characterizes the relationships between various specific pathogens and ctcl, and discusses some of the difficulties in establishing a causal link between infectious agents and ctcl carcinogenesis. researchers have evaluated ctcl specimens for evidence of infection with a ...201723806159
kaposi's sarcoma-associated herpesvirus polyadenylated nuclear rna: a structural scaffold for nuclear, cytoplasmic and viral proteins.kaposi's sarcoma-associated herpes virus (kshv) polyadenylated nuclear (pan) rna facilitates lytic infection, modulating the cellular immune response by interacting with viral and cellular proteins and dna. although a number nucleoprotein interactions involving pan have been implicated, our understanding of binding partners and pan rna binding motifs remains incomplete. herein, we used shape-mutational profiling (shape-map) to probe pan in its nuclear, cytoplasmic or viral environments or follow ...201728383682
kaposi's sarcoma-associated herpesvirus orf34 is essential for late gene expression and virus production.kaposi's sarcoma-associated herpesvirus (kshv) is the causative agent of kaposi's sarcoma, primary effusion lymphoma, and multicentric castleman's disease. kshv establishes a life-long infection in its host and alternates between a latent and lytic infection state. during lytic infection, lytic-related genes are expressed in a temporal manner and categorized as immediate early, early, and late gene transcripts. orf34 is an early-late gene that interacts with several viral transcription-associate ...201728336944
multicenter prospective study for laboratory diagnosis of hhv8 infection in solid organ donors and transplant recipients and evaluation of the clinical impact after transplantation.we performed serological and molecular pretransplant screening in solid organ transplant (sot) donors and recipients in north-central italy and a surveillance program for human herpes virus 8 (hhv8) infection after transplant, aiming to establish an optimal management of hhv8 infection in sot recipients.201728333859
classic kaposi sarcoma in an hiv-negative han chinese man: a case report.kaposi sarcoma (ks) is a multifocal angioproliferativetumor of endothelial origin. despite nearly identicalclinical and histopathologic presentations, ks isclassified into four distinct varieties: classic/sporadic,aids-associated, african/endemic, and iatrogenic. allsubtypes are invariably linked to human herpesvirus-8(hhv-8) and show a male predilection. classic kaposisarcoma is exceedingly rare in the asian populationand its incidence varies by region and ethnic grouppredominance. a study in t ...201728329475
diagnosis and treatment of kaposi sarcoma.kaposi sarcoma (ks) is the most common neoplasm of people living with hiv today. in sub-saharan africa, ks is among the most common cancers in men, overall. not only hiv-positive individuals present with ks; any immune compromised person infected with ks-associated herpesvirus (kshv) or human herpesvirus 8 is at risk: the elderly, children in kshv-endemic areas, and transplant recipients. ks diagnosis is based on detection of the viral protein latency-associated nuclear antigen (lana) in the bio ...201728324233
mediastinal syndrome from plasmablastic lymphoma in human immunodeficiency virus and human herpes virus 8 negative patient with polycythemia vera: a case report.plasmoblastic lymphoma is a rare and aggressive subtype of diffuse large b cell lymphoma, which occurs usually in the jaw of immunocompromised subjects.201728320457
mycosis fungoides and kaposi's sarcoma association in an hiv-negative patient.the association of mycosis fungoides and kaposi's sarcoma in hiv-negative patients is a rare phenomenon. the presence of human herpesvirus 8 (hhv-8) - associated with all forms of kaposi's sarcoma - has also been recently identified in mycosis fungoides lesions. however, a causal association between hhv-8 and the onset of mycosis fungoides has not been established yet. the present case reports a patient who developed kaposi's sarcoma lesions after a two-year uvb phototherapy to treat a mycosis f ...201728300912
increased frequency and vasculogenic potential of endothelial colony-forming cells in patients with kaposi's sarcoma.kaposi's sarcoma (ks) is characterized by hyperproliferation of spindle cells that have an endothelial origin and assume their characteristic features upon infection with human herpesvirus-8 (hhv8), the causative agent for ks. the multifocal nature of ks suggests that spindle cells derive from circulating hhv8-infected precursors that yet lack identification. we investigated whether ecfcs obtained from ks patients may be putative precursors of spindle cells, by assessing whether their in vitro b ...201728288847
acquired immune deficiency syndrome-associated kaposi sarcoma in a child presenting as a solitary plantar hyperkeratotic plaque.acquired immune deficiency syndrome (aids)-associated kaposi sarcoma (ks) among the pediatric population is a rare entity in north america and europe, and its cutaneous manifestations are not well defined in the literature. the investigators report the case of a boy with an aids-associated ks presenting as an infiltrated hyperkeratotic plaque of the plantar arch.201728288525
glycolysis, glutaminolysis and fatty acid synthesis are required for distinct stages of kshv lytic replication.kaposi's sarcoma-associated herpesvirus (kshv) is the etiologic agent of kaposi's sarcoma (ks). kshv infection induces and requires multiple metabolic pathways, including glycolysis, glutaminolysis and fatty acid synthesis (fas) for the survival of latently infected endothelial cells. to determine the metabolic requirements for productive kshv infection, we induced lytic replication in the presence of inhibitors of different metabolic pathways. we found that glycolysis, glutaminolysis and fas ar ...201728275189
kaposi's sarcoma after t-cell costimulation blockade with abatacept in rheumatoid arthritis: a case report.kaposi's sarcoma (ks) is a malignant neoplasm caused by hhv-8, a pathogen that leads to endothelial cell transformation when host defences are weakened.201728262965
endoscopic appearance of oropharyngeal and upper gi kaposi's sarcoma in an immunocompromised patient.introduction. kaposi's sarcoma (ks) usually manifests as a cutaneous disease but gi manifestation is often rare. it is associated with human herpes virus-8 (hhv-8) and seen in immunocompromised patients. in the usa, use of highly active antiretroviral therapy (haart) has drastically reduced incidence of ks in hiv patients. case presentation. a 65-year-old male with human immunodeficiency virus (hiv) was admitted to the intensive care unit (icu) with cardiopulmonary arrest secondary to hyperkalem ...201728261507
seroprevalence of kaposi's sarcoma-associated herpesvirus among hiv-infected uygurs in xinjiang, china.kaposi's sarcoma-associated herpesvirus (kshv) is the etiological agent of kaposi's sarcoma (ks), which primarily affects human immunodeficiency virus (hiv)-infected adults with advanced immunodeficiency. xinjiang province in china is an endemic area for kaposi's sarcoma (ks), however, currently, only limited prevalence data for kshv infection in hiv-infected individuals living in this endemic area is available. a cross-sectional study of 86 hiv positive participants was conducted in xinjiang, c ...201728252177
developmental therapeutics implications of next-generation sequencing in human herpesvirus 8-negative castleman disease. 201728241212
hepatic kaposi sarcoma: a case report and review of the literature.kaposi sarcoma (ks) is an aggressive cancer caused by human herpesvirus-8, primarily seen in immunocompromised patients. as opposed to the well-described cutaneous manifestations and pulmonary complications of ks, hepatic ks is rarely reported before death as most patients with hepatic ks do not manifest symptoms or evidence of liver injury. in patients with acquired immune deficiency syndrome, hepatic involvement of ks is present in 12%-24% of the population on incidental imaging and in approxi ...201728217255
pulmonary kaposi sarcoma with osseous metastases in an human immunodeficiency virus (hiv) patient: a remarkable response to highly active antiretroviral therapy.background kaposi sarcoma (ks) is known to involve the mucocutaneous tissues and the aero-digestive tracts. in acquired immune deficiency syndrome (aids) patients, ks has an aggressive course and carries poor prognosis. we present a case of pulmonary ks with osseous metastases as the first presentation of human immunodeficiency virus (hiv) infection in a young male. the lesions impressively decreased in size and numbers following initiation of highly active antiretroviral therapy (haart). case r ...201728216610
elevated serum interferon γ-induced protein 10 kda is associated with tafro syndrome.multicentric castleman disease (mcd) is a heterogeneous lymphoproliferative disorder. it is characterized by inflammatory symptoms, and interleukin (il)-6 contributes to the disease pathogenesis. human herpesvirus 8 (hhv-8) often drives hypercytokinemia in mcd, although the etiology of hhv-8-negative mcd is idiopathic (imcd). a distinct subtype of imcd that shares a constellation of clinical features including thrombocytopenia (t), anasarca (a), fever (f), reticulin fibrosis (r), and organomegal ...201728205564
cutaneous plasmacytosis resembling pityriasis rosea in a 66-year-old white woman: a rare disease presenting in an unusual patient demographic. 201728203625
oncogenic role of tumor viruses in humans.viruses are the intracellular pathogens that reproduce only in the living cell and manipulate the cellular machinery to produce more viruses. viral replications can affect cellular genes of the host in multiple cancerous ways. approximately, 20% of all human oncogenesis is caused by cancer-causing viruses known as oncoviruses. viral infection causes chronic inflammation leading to cell death, uncontrollable proliferation, and modulated expression of some of the regulatory proteins. oncogenesis i ...201727830995
prevalence of human herpesvirus-8 and bk polyoma virus infections in end-stage renal disease and the influence of renal transplantation.viral infections lead to significant morbidity and mortality in kidney transplant recipients. we evaluated 49 kidney transplant recipients for human herpesvirus 8 (hhv-8) and bk polyomavirus infections in conjunction with data obtained from 43 donors. the seroprevalence of hhv-8 was 6.9% in donors and 12.2% in recipients. hhv-8 dna was detected below the limit of quantification (<5000 copies/ml) in a recipient with hhv-8 seropositivity at the pretransplant period and was undetectable at month 3 ...201728340807
virus reactivations after autologous hematopoietic stem cell transplantation detected by multiplex pcr assay.several studies have indicated that viral reactivations following allogeneic hematopoietic stem cell transplantation (allo-hsct) are frequent, but viral reactivations after autologous hsct (auto-hsct) have not been investigated in detail. we performed multiplex polymerase chain reaction (pcr) assay to examine multiple viral reactivations simultaneously in 24 patients undergoing auto-hsct between september 2010 and december 2012. weekly whole blood samples were collected from pre- to 42 days post ...201727364410
establishment of multiplex solid-phase strip pcr test for detection of 24 ocular infectious disease pathogens.to establish and evaluate a new multiplex solid-phase strip polymerase chain reaction (strip pcr) for concurrent detection of common ocular infectious disease pathogens.201728282487
human herpesviruses as copathogens of hiv infection, their role in hiv transmission, and disease progression.of eight human herpesviruses (hhvs), often, only herpes simplex virus types 1 (hsv-1) and 2 (hsv-2) find mention in medical literature as both of these viruses are commonly associated with genital lesions and oral ulcers, commonly known as cold sores. however, role of human herpesviruses as copathogens and in aggravation and in the transmission of other human diseases, especially the acquired immunodeficiency syndrome (hiv/aids) has only very recently been recognized. therefore, screening and tr ...201727013807
long-term nitrite inhalant exposure and cancer risk in men who have sex with men: a prospective cohort study.nitrite inhalants (poppers) are commonly used recreational drugs among men who have sex with men (msm) and were previously associated with elevated rates of high-risk sexual behavior, hiv and hhv-8 seroconversion, and transient immunosuppressive effects in experimental models. whether long-term popper use is associated with cancer risk among msm in the haart era is unclear.201728323751
ebv-associated but hhv8-unrelated double-hit effusion-based lymphoma.effusion-based lymphoma is a rare and unique type of large b-cell lymphoma presenting in effusion without a mass lesion. it shares many clinicopathological features with primary effusion lymphoma (pel), but is distinct from pel by the absence of hhv8 association. double hit lymphoma (dhl) is an aggressive b-cell lymphoma, defined by concurrent rearrangement of myc and bcl2 or bcl6. dhl often presents as lymphadenopathy or an extranodal mass, but rarely occurs in effusion. here we report a 61-yea ...201727888664
clinical course of disseminated kaposi sarcoma in a hiv and hepatitis b co-infected heterosexual male.aids associated kaposi sarcoma (aids-ks) was first reported from india in 1993. since then only 16 cases have been reported. three of them had proven human herpesvirus 8 (hhv-8) infection. we report a case of disseminated ks in a heterosexual male from india with hiv, hepatitis b and hhv-8 infection. he was given six cycles of chemotherapy with liposomal doxorubicin over three months to which he showed a good response. the case highlights the clinical course and management of a hhv-8 positive di ...201726225336
high seroprevalence of human herpesvirus 8 and herpes simplex virus 2 infections in men who have sex with men in shanghai, china.men who have sex with men (msm) are an important risk group for human immunodeficiency virus (hiv) and at high-risk of herpesvirus infection. however, limited information on epidemiologic patterns of hhv8 and hsv2 among msm is available in mainland china. a cross-sectional study of 486 participants was performed in shanghai, china from january 2013 to december 2014 to explore epidemiologic features of hhv8 and hsv2 among msm. serum samples were collected and tested for hhv8 by immunofluoresence ...201727769110
evidence for a mesothelial origin of body cavity effusion lymphomas.primary effusion lymphoma (pel) is a kaposi's sarcoma herpes virus (kshv)-induced lymphoma that typically arises in body cavities of hiv-infected patients. pel cells are often co-infected with epstein-barr virus (ebv). "pel-like" lymphoma is a kshv-unrelated lymphoma that arises in body cavities of hiv-negative patients. "pel-like" lymphoma is sometimes ebv positive. the derivation of pel/"pel-like" cells is unclear.201728376153
kshv-associated and ebv-associated germinotropic lymphoproliferative disorder: new findings and review of the literature.we report 2 cases of kaposi sarcoma-associated herpesvirus (kshv)-and epstein-barr virus (ebv) associated germinotropic lymphoproliferative disorder. both cases arose in patients from regions endemic for kshv, cape verde, and the democratic republic of the congo, presenting as localized lymphadenopathy. the affected lymph nodes showed colonization of the follicles by clusters of large atypical plasmablasts, but also showed regressive changes with vascular proliferation and interfollicular plasma ...201728248818
regulatory t cell effect on cd8(+) t cell responses to human herpesvirus 8 infection and development of kaposi's sarcoma.we assessed cd8(+) t cell reactivity to human herpesvirus 8 (hhv-8; kaposi's sarcoma [ks]-associated herpesvirus) and the role of cd4(+)cd25(hi)foxp3(+) regulatory t cells (treg) in hhv-8- and hiv-coinfected participants of the multicenter aids cohort study who did or did not develop ks. there were similarly low cd8(+) t cell interferon-γ responses to mhc class i-restricted epitopes of hhv-8 lytic and latent proteins over 5.7 years before ks in participants who developed ks compared to those who ...201728121161
hhv8-related lymphoid proliferations: a broad spectrum of lesions from reactive lymphoid hyperplasia to overt lymphoma.human herpesvirus 8 (hhv8)-associated lymphoid proliferations are uncommon and poorly characterized disorders mainly affecting immunosuppressed patients, especially with hiv infection. they encompass different diseases with overlapping features that complicate their classification. in addition, the role of hhv8 in reactive lymphoid hyperplasia is not well known. to analyze the clinicopathological spectrum of these lesions, we have reviewed 66 biopsies of 61 patients with hhv8 infection. all case ...201728084335
inkt and memory b-cell alterations in hhv-8 multicentric castleman disease.human herpesvirus 8 (hhv-8) is the causative agent of kaposi sarcoma (ks) and multicentric castleman disease (mcd), a life-threatening, virally induced b-cell lymphoproliferative disorder. hhv-8 is a b-lymphotropic γ-herpesvirus closely related to the epstein-barr virus (ebv). invariant natural killer t (inkt) cells are innate-like t cells that play a role in antiviral immunity, specifically in controlling viral replication in ebv-infected b cells. decline of inkt cells is associated with age or ...201728060720
niclosamide inhibits lytic replication of epstein-barr virus by disrupting mtor activation.infection with the oncogenic γ-herpesviruses epstein-barr virus (ebv) and kaposi's sarcoma-associated herpesvirus (kshv) cause several severe malignancies in humans. inhibition of the lytic replication of ebv and kshv eliminates the reservoir of persistent infection and transmission, consequently preventing the occurrence of diseases from the sources of infection. antiviral drugs are limited in controlling these viral infectious diseases. here, we demonstrate that niclosamide, an old anthelminti ...201727939840
human herpesvirus-8 and human cytomegalovirus infections in bowen's disease: is there any association? 201728366922
novel chemokine-based immunotoxins for potent and selective targeting of cytomegalovirus infected cells.immunotoxins as antiviral therapeutics are largely unexplored but have promising prospective due to their high selectivity potential and their unparalleled efficiency. one recent example targeted the virus-encoded g protein-coupled receptor us28 as a strategy for specific and efficient treatment of human cytomegalovirus (hcmv) infections. us28 is expressed on virus-infected cells and scavenge chemokines by rapid internalization. the chemokine-based fusion-toxin protein (ftp) consisted of a varia ...201728251165
tentative diagnostic criteria and disease severity classification for castleman disease: a report of the research group on castleman disease in japan.to determine the tentative diagnostic criteria and disease severity classification for castleman disease (cd) and describe the clinical and pathologic features among human herpesvirus 8 (hhv-8) negative idiopathic multicentric cd (imcd) in the japanese population.201828880697
viral and cellular n6-methyladenosine and n6,2'-o-dimethyladenosine epitranscriptomes in the kshv life cycle.n6-methyladenosine (m6a) and n6,2'-o-dimethyladenosine (m6am) modifications (m6a/m) of messenger rna mediate diverse cellular functions. oncogenic kaposi's sarcoma-associated herpesvirus (kshv) has latent and lytic replication phases that are essential for the development of kshv-associated cancers. to date, the role of m6a/m in kshv replication and tumorigenesis is unclear. here, we provide mechanistic insights by examining the viral and cellular m6a/m epitranscriptomes during kshv latent and l ...201829109479
treatment of kaposi sarcoma herpesvirus-associated multicentric castleman disease.kaposi sarcoma herpesvirus (kshv)-associated multicentric castleman disease (mcd) is a rare, polyclonal lymphoproliferative disorder characterized by flares of inflammatory symptoms, edema, cytopenias, lymphadenopathy, and splenomegaly. diagnosis requires a lymph node biopsy. pathogenesis is related to dysregulated inflammatory cytokines, including human and viral interleukin-6. rituximab alone or in combination with chemotherapy, such as liposomal doxorubicin, has led to an overall survival of ...201829157621
castleman disease pathogenesis.castleman disease (cd) describes a group of heterogeneous disorders with common lymph node histopathologic features, including atrophic or hyperplastic germinal centers, prominent follicular dendritic cells, hypervascularization, polyclonal lymphoproliferation, and/or polytypic plasmacytosis. the cause and pathogenesis of the four subtypes of cd (unicentric cd; human herpesvirus-8-associated multicentric cd; polyradiculoneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, a ...201829157613
epidemiology of castleman disease.castleman disease is a rare entity, including unicentric castleman disease (ucd), human herpesvirus-8 plus castleman disease (hhv-8+mcd), and idiopathic multicentric castleman disease (imcd). ucd is the most common at 16 per million person years and occurs at every age. hhv-8+mcd incidence varies widely, mostly affecting human immunodeficiency virus-positive men. imcd is likely a more heterogeneous disease with an estimated incidence of 5 per million person years. improved definitions should imp ...201829157611
the full spectrum of castleman disease: 273 patients studied over 20 years.the spectrum of castleman disease (cd) has considerably extended since its first description in 1956. recently, an international collaborative working group has reached consensus on the diagnostic criteria and classification of cd. we herein report 273 patients with lymph node histopathology consistent with cd and investigate the newly established diagnostic criteria. twenty of these patients with castleman-like histopathology were removed from analyses, because they were diagnosed with an exclu ...201829143319
a conserved eph family receptor-binding motif on the gh/gl complex of kaposi's sarcoma-associated herpesvirus and rhesus monkey rhadinovirus.kaposi's sarcoma-associated herpesvirus (kshv) is a human oncogenic virus associated with kaposi's sarcoma and two b-cell malignancies. the rhesus monkey rhadinovirus (rrv) is a virus of nonhuman primates that is closely related to kshv. eph family receptor tyrosine kinases (ephs) are cellular receptors for the gh/gl glycoprotein complexes of both kshv and rrv. through sequence analysis and mutational screens, we identified conserved residues in the n-terminal domain of kshv and rrv glycoprotein ...201829432452
seroprevalence of human herpesvirus 8 and its impact on the hemoglobin level in patients of end stage of renal diseases.the incidence of kaposi's sarcoma (ks) is increasing among renal transplant recipients. patients with end-stage renal disease (esrd) are immunocompromised and are candidates for renal transplantation, but hhv8 seroprevalence in esrd patients has not been well documented. a cross-sectional study of 286 esrd patients and 281 matched subjects without kidney disease was conducted at the first people's hospital of huzhou, zhejiang province to explore the epidemiologic features of hhv8 among esrd pati ...201828876458
il-10 promoter transactivation by the viral k-rta protein involves the host-cell transcription factors, specificity proteins 1 and 3.kaposi's sarcoma-associated herpesvirus (kshv)/human herpesvirus-8 (hhv-8) causes a persistent infection, presenting latent and lytic replication phases during its life cycle. kshv-related diseases are associated with deregulated expression of inflammatory cytokines, including il-6 and il-10, but the mechanisms underlying this dysregulation are unclear. herein, we report a molecular mechanism for kshv-induced il-10 gene expression. kshv replication and transcription activator (k-rta) is a molecu ...201829184003
two herpesviral noncoding pan rnas are functionally homologous but do not associate with common chromatin loci.during lytic replication of kaposi's sarcoma-associated herpesvirus (kshv), a nuclear viral long noncoding rna known as pan rna becomes the most abundant polyadenylated transcript in the cell. knockout or knockdown of kshv pan rna results in loss of late lytic viral gene expression and, consequently, reduction of progeny virion release from the cell. here, we demonstrate that knockdown of pan rna from the related rhesus macaque rhadinovirus (rrv) phenocopies that of kshv pan rna. these two pan r ...201830383841
macaque homologs of kaposi's sarcoma-associated herpesvirus (kshv) infect germinal center lymphoid cells, epithelial cells in skin and gastrointestinal tract and gonadal germ cells in naturally infected macaques.we developed a set of rabbit antisera to characterize infections by the macaque rv2 rhadinovirus homologs of kshv. we analyzed tissues from rhesus and pig-tailed macaques naturally infected with rhesus rhadinovirus (rrv) or macaca nemestrina rhadinovirus 2 (mnerv2). our study demonstrates that rv2 rhadinoviruses have a tropism for epithelial cells, lymphocytes and gonadal germ cells in vivo. we observed latent infections in both undifferentiated and differentiated epithelial cells with expressio ...201829689462
global epidemiology of human herpesvirus 8 in men who have sex with men: a systematic review and meta-analysis.men who have sex with men (msm) were highly vulnerable to hiv/aids and human herpes virus 8 (hhv8), while the epidemiologic features of hhv8 among msm remain obscure. we therefore performed a systematic review and meta-analysis to assess the burden of hhv8 in msm. electronic databases were searched for publications on hhv8 epidemiologic characteristics among msm. random-effect meta-analysis was applied to combine the hhv8 seroprevalence in msm and odds ratios (ors) for associated risk factors. m ...201828975631
arctigenin induces the apoptosis of primary effusion lymphoma cells under conditions of glucose deprivation.kaposi's sarcoma-associated herpesvirus (kshv) is the causative agent of primary effusion lymphoma (pel) and kaposi's sarcoma. pel is a type of non-hodgkin's b-cell lymphoma, affecting immunosuppressed individuals, such as post-transplant or aids patients. however, since pel is resistant to chemotherapeutic regimens, new effective treatment strategies are required. arctigenin, a natural lignan compound found in the plant arctium lappa, has been widely investigated as a potential anticancer agent ...201829207179
kaposi sarcoma presenting shortly after primary infection by hiv and human herpesvirus-8. 201829256918
rna-seq of kaposi's sarcoma reveals alterations in glucose and lipid metabolism.kaposi's sarcoma-associated herpesvirus (kshv) is the etiologic agent of kaposi's sarcoma (ks). it is endemic in a number of sub-saharan african countries with infection rate of >50%. the high prevalence of hiv-1 coupled with late presentation of advanced cancer staging make ks the leading cancer in the region with poor prognosis and high mortality. disease markers and cellular functions associated with ks tumorigenesis remain ill-defined. several studies have attempted to investigate changes of ...201829352292
human herpesvirus 8 interferon regulatory factors 1 and 3 mediate replication and latency activities via interactions with usp7 deubiquitinase.human herpesvirus 8 (hhv-8) encodes four viral interferon regulatory factors (virfs 1-4) that likely function to suppress innate immune and cellular stress responses through inhibitory interactions with various cellular proteins involved in these activities. it is notable that virfs 1 and 4 have been reported to interact with the deubiquitinase usp7, substrates of which include p53 and p53-targeting and destabilizing ubiquitin e3 ligase mdm2. structural studies of virf-1 and virf-4 usp7-binding ...201829343584
structure and mutagenesis reveal essential capsid protein interactions for kshv replication.kaposi's sarcoma-associated herpesvirus (kshv) causes kaposi's sarcoma, a cancer that commonly affects patients with aids and which is endemic in sub-saharan africa. the kshv capsid is highly pressurized by its double-stranded dna genome, as are the capsids of the eight other human herpesviruses. capsid assembly and genome packaging of herpesviruses are prone to interruption and can therefore be targeted for the structure-guided development of antiviral agents. however, herpesvirus capsids-compr ...201829342139
deregulation of hdac5 by viral interferon regulatory factor 3 plays an essential role in kaposi's sarcoma-associated herpesvirus-induced lymphangiogenesis.kaposi's sarcoma-associated herpesvirus (kshv) is the etiologic agent for kaposi's sarcoma (ks), which is one of the most common hiv-associated neoplasms. the endothelium is the thin layer of squamous cells where vascular blood endothelial cells (becs) line the interior surface of blood vessels and lymphatic endothelial cells (lecs) are in direct contact with lymphatic vessels. the ks lesions contain a prominent compartment of neoplastic spindle morphology cells that are closely related to lecs. ...201829339432
acroangiodermatitis mimicking kaposi's sarcoma in an hiv-positive man.kaposi's sarcoma (ks) is the commonest human immunodeficiency virus (hiv)-related malignancy with its characteristic cutaneous morphological appearance and histopathological features. however, it can be simulated by other co-morbid opportunistic infections and unrelated dermatological conditions. we describe such a case of acroangiodermatitis in an hiv co-infected man, based on exclusion of ks histologically and the absence of human herpesvirus 8, the causative agent of ks.201829334884
human herpesvirus 8-associated inflammatory cytokine syndrome. 201829322174
kaposi's sarcoma-associated herpesvirus k8 is an rna binding protein that regulates viral dna replication in coordination with a noncoding rna.kshv lytic replication and constant primary infection of fresh cells are crucial for viral tumorigenicity. virus-encoded b-zip family protein k8 plays an important role in viral dna replication in both viral reactivation and de novo infection. the mechanism underlying the functional role of k8 in the viral life cycle is elusive. here we report that k8 is a rna binding protein, which also associates with many proteins including other rna binding proteins. many k8-involved protein-protein interact ...201829321307
the unholy trinity of human herpesvirus 8-associated malignancy in a person living with hiv-1. 201829309348
kshv episomes reveal dynamic chromatin loop formation with domain-specific gene regulation.the three-dimensional structure of chromatin organized by genomic loops facilitates rna polymerase ii access to distal promoters. the kaposi's sarcoma-associated herpesvirus (kshv) lytic transcriptional program is initiated by a single viral transactivator, k-rta. here we report the kshv genomic structure and its relationship with k-rta recruitment sites using capture hi-c analyses. high-resolution 3d viral genomic maps identify a number of direct physical, long-range, and dynamic genomic intera ...201829302027
gamma-herpesvirus colonization of the spleen requires lytic replication in b cells.gamma-herpesviruses infect lymphocytes and cause lymphocytic cancers. murid herpesvirus-4 (muhv-4), epstein-barr virus and the kaposi's sarcoma-associated herpesvirus all infect b cells. latent infection can spread by b cell recirculation and proliferation, but whether this alone achieves systemic infection is unclear. to test the need of muhv-4 for lytic infection in b cells we flanked its essential orf50 lytic transactivator with loxp sites, then infected mice with b cell-specific cre expressi ...201829343572
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