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kaposi's sarcoma-associated herpesvirus infection of blood endothelial cells induces lymphatic differentiation.kaposi's sarcoma-associated herpesvirus (kshv) is necessary for ks, a highly vascularized tumor predominated by endothelial-derived spindle cells that express markers of lymphatic endothelium. following kshv infection of time cells, an immortalized human dermal microvascular endothelial cell (dmvec) line, expression of many genes specific to lymphatic endothelium, including vegfr3, podoplanin, lyve-1, and prox-1, is significantly increased. increases in vegfr3 and podoplanin protein are also dem ...200415380353
rna-based gene transfer for adult stem cells and t cells.electroporation of mrna has become an established method for gene transfer into dendritic cells for immunotherapeutic purposes. however, many more cell types and applications might benefit from an efficient mrna-based gene transfer method. in this study, we investigated the potential of mrna-based gene transfer to induce short-term transgene expression in adult stem cells and activated t cells, based on electroporation with mrna encoding the enhanced green fluorescent protein. the results show e ...200415385941
disruption of kaposi's sarcoma-associated herpesvirus latent nuclear antigen leads to abortive episome persistence.latent nuclear antigen (lna) is implicated in kaposi's sarcoma-associated herpesvirus (kshv) episome persistence. lna colocalizes with kshv episomes on chromosomes in metaphase, and it maintains the stability and replication of kshv terminal repeat-containing plasmids. in this study, we examined the function of lna in episome persistence in the context of full-length kshv genome by mutagenesis analysis. we generated a kshv mutant, bac36-deltalna, with lna disrupted by transposon-based mutagenesi ...200415452232
[a gamma, from alpha to omega...]. 200415460457
the kaposi's sarcoma-associated herpesvirus k-bzip protein represses transforming growth factor beta signaling through interaction with creb-binding protein.kaposi's sarcoma (ks)-associated herpesvirus (kshv) is involved in the pathogenesis of ks, primary effusion lymphoma, and multicentric castleman's disease. k-bzip, the protein encoded by the open reading frame k8 of kshv, is a member of the basic region-leucine zipper family of transcription factors. we studied the mechanisms that underlie kshv-induced oncogenesis by investigating whether k-bzip perturbs signaling through transforming growth factor beta (tgf-beta), which inhibits proliferation o ...200415467747
evidence for both lytic replication and tightly regulated human herpesvirus 8 latency in circulating mononuclear cells, with virus loads frequently below common thresholds of detection.to address whether human herpesvirus 8 (hhv-8) dna in peripheral blood mononuclear cells (pbmcs) might be the product of latent or lytic infection and to shed light on sporadic detection of hhv-8 dna in individuals seropositive for the virus, we studied the frequency of infected cells, total virus load, and virus load per infected cell in pbmcs from men coinfected with hhv-8 and human immunodeficiency virus (hiv), some of whom had kaposi's sarcoma. the low frequencies of infected cells detected ...200415479812
orc, mcm, and histone hyperacetylation at the kaposi's sarcoma-associated herpesvirus latent replication origin.the viral genome of kaposi's sarcoma-associated herpesvirus (kshv) persists as an extrachromosomal plasmid in latently infected cells. the kshv latency-associated nuclear antigen (lana) stimulates plasmid maintenance and dna replication by binding to an approximately 150-bp region within the viral terminal repeats (tr). we have used chromatin immunoprecipitation assays to demonstrate that lana binds specifically to the replication origin sequence within the kshv tr in latently infected cells. th ...200415507644
ocular manifestations of aids: new considerations for patients using highly active anti-retroviral therapy (haart).background: highly active anti-retroviral therapy (haart) effectively restores the immune system and lowers the viral load in patients with human immunodeficiency virus (hiv) and acquired immunodeficiency syndrome (aids). since widespread use of haart drugs began in 1996, many aids patients are living longer and enjoying a higher quality of life. the incidence of aids-related ophthalmic infections, such as cytomegalovirus (cmv) retinitis, have declined sharply. aids patients with cmv are less li ...200415508863
viral load of human herpesvirus 8 (hhv-8) in the circulatory blood cells correlates with clinical progression in a patient with hhv-8-associated solid lymphoma with aids-associated kaposi's sarcoma.we encountered a case of a rapidly progressive hhv-8-associated solid lymphoma with aids-associated kaposi's sarcoma (ks). hhv-8 dna load in whole blood cells was analyzed quantitatively by real-time pcr using amplification of the hhv-8-encoded orf26 gene. ours is the first observation that the rapid increase in the hhv-8 viral load (from 1.9x10(4) copies/microg to 1.6x10(6) copies/microg in 40 days) in conjunction with low cd4+ cell counts was accompanied by an accelerated clinical disease prog ...200415512828
the prototype gamma-2 herpesvirus nucleocytoplasmic shuttling protein, orf 57, transports viral rna through the cellular mrna export pathway.hvs (herpesvirus saimiri) is the prototype gamma-2 herpesvirus. this is a subfamily of herpesviruses gaining importance since the identification of the first human gamma-2 herpesvirus, kaposi's sarcoma-associated herpesvirus. the hvs orf 57 (open reading frame 57) protein is a multifunctional transregulatory protein homologous with genes identified in all classes of herpesviruses. recent work has demonstrated that orf 57 has the ability to bind viral rna, shuttles between the nucleus and cytopla ...200515537388
the dna architectural protein hmgb1 facilitates rta-mediated viral gene expression in gamma-2 herpesviruses.replication and transcription activator (rta), an immediate-early gene product of gamma-2 herpesviruses including kaposi's sarcoma-associated herpesvirus (kshv) and murine gamma herpesvirus 68 (mhv-68), plays a critical role in controlling the viral life cycle. rta acts as a strong transcription activator for several downstream genes of kshv and mhv-68 through direct dna binding, as well as via indirect mechanisms. hmgb1 (also called hmg-1) protein is a highly conserved nonhistone chromatin prot ...200415542646
raf-induced vascular endothelial growth factor augments kaposi's sarcoma-associated herpesvirus infection.recombinant green fluorescent protein encoding kaposi's sarcoma-associated herpesvirus (rkshv.152) infection of beta-estradiol stimulated human foreskin fibroblasts (hff) or hff/deltab-raf([ff]):er (expressing a weaker form of b-raf) could be enhanced to levels comparable to that of hff/deltab-raf([dd]):er cells by pretreating cells with soluble vascular endothelial growth factor (vegf). conversely, vegf expression and infection efficiency typically observed in beta-estradiol stimulated hff/delt ...200415542692
epidemiological characteristics of human herpesvirus-8 infection in a large population of antenatal women in zambia.comprehensive data describing epidemiological characteristics of the human herpesvirus-8 or kaposi's sarcoma-associated herpesvirus (hhv-8 or kshv) infection among pregnant women in a central sub-saharan africa are not available. this study determined virus prevalence estimates and the risk factors associated with hhv-8 infection. cross-sectional, enrollment visit data were analyzed from a prospective cohort study of perinatal transmission of hhv-8 in lusaka, zambia. exposure data were obtained ...200515543582
stimulation of kaposi's sarcoma-associated herpesvirus viremia during hematopoietic stem cell mobilization with filgrastim.the effects of hematopoietic stem cell (hsc) mobilization on kaposi's sarcoma-associated herpesvirus (kshv) were evaluated in three kshv and human immunodeficiency virus type 1 co-infected subjects. kshv dna was not detected in purified cd34+ cell preparations from the period of filgrastim treatment. however, two of 3 subjects had transiently increased cell-free plasma kshv dna during filgrastim treatment. peak plasma kshv dna (2,600 and 4,300 copies/ml) occurred on day 4 and declined to below t ...200415551282
plasmablastic lymphomas and plasmablastic plasma cell myelomas have nearly identical immunophenotypic profiles.plasmablastic lymphoma is an aggressive neoplasm that shares many cytomorphologic and immunophenotypic features with plasmablastic plasma cell myeloma. however, plasmablastic lymphoma is listed in the world health organization (who) classification as a variant of diffuse large b-cell lymphoma. to characterize the relationship between plasmablastic lymphoma and plasmablastic plasma cell myeloma, we performed immunohistochemistry using a large panel of b-cell and plasma cell markers on nine cases ...200515578069
immune reconstitution inflammatory syndrome associated with kaposi sarcoma during potent antiretroviral therapy.rapidly progressive kaposi sarcoma (ks) lesions with lymphadenopathy and tissue swelling occurred in a patient during antiretroviral treatment, despite an increased cd4(+) lymphocyte count and decreased hiv-1 level and ks-associated herpesvirus replication, suggesting immune reconstitution inflammatory syndrome. inflammation resolved coincident with decreases in the cd4(+) lymphocyte count during paclitaxel treatment, whereas ks cleared only after prolonged antiretroviral therapy and chemotherap ...200415578411
epstein-barr virus-encoded bilf1 is a constitutively active g protein-coupled receptor.both beta- and gammaherpesviruses encode g protein-coupled receptors (gpcrs) with unique pharmacological phenotypes and important biological functions. an example is orf74, the gamma2-herpesvirus kaposi's sarcoma-associated herpesvirus (kshv)-encoded gpcr, which is highly constitutively active and considered the key oncogene in kaposi's sarcoma pathogenesis. in contrast, the current annotation of the epstein-barr virus (ebv) genome does not reveal any gpcr homolog encoded by this human oncogenic ...200515596846
receptor modulation in viral replication: hiv, hsv, hhv-8 and hpv: same goal, different techniques to interfere with mhc-i antigen presentation.evasion of host immunity is a common objective of viruses that cause chronic infections. viruses involved in sexually transmitted infections constitute no exception to this phenomenon. hiv, hpv, hsv, and hhv-8 subvert the class i major histocompatibility complex (mhc-i) antigen presentation pathway, thereby evading the cellular immune response. although the goal of these viruses is the same and efficient mhc-i downregulation in infected cells is achieved, their techniques vary considerably. whet ...200515609505
virion proteins of kaposi's sarcoma-associated herpesvirus.the proteins that compose a herpesvirus virion are thought to contain the functional information required for de novo infection, as well as virion assembly and egress. to investigate functional roles of kaposi's sarcoma-associated herpesvirus (kshv) virion proteins in viral productive replication and de novo infection, we attempted to identify virion proteins from purified kshv by a proteomic approach. extracellular kshv virions were purified from phorbol-12-tetradecanoate-13-acetate-induced bcb ...200515613308
kaposi's sarcoma-associated herpesvirus modulates microtubule dynamics via rhoa-gtp-diaphanous 2 signaling and utilizes the dynein motors to deliver its dna to the nucleus.human herpesvirus 8 (hhv-8; also called kaposi's sarcoma-associated herpesvirus), which is implicated in the pathogenesis of kaposi's sarcoma (ks) and lymphoproliferative disorders, infects a variety of target cells both in vivo and in vitro. hhv-8 binds to several in vitro target cells via cell surface heparan sulfate and utilizes the alpha3beta1 integrin as one of its entry receptors. interactions with cell surface molecules induce the activation of host cell signaling cascades and cytoskeleta ...200515613346
distinct subsets of primary effusion lymphoma can be identified based on their cellular gene expression profile and viral association.primary effusion lymphomas (pels) are specifically associated with kaposi's sarcoma-associated herpesvirus (kshv) infection and most frequently occur in human immunodeficiency virus (hiv)-positive individuals as lymphomatous effusions in the serous cavities without a detectable solid tumor mass. most pels have concomitant epstein-barr virus (ebv) infection, suggesting that ebv is an important pathogenetic cofactor, although other as yet unidentified cofactors, such as cellular genetic alteration ...200515613351
the rationale for pathogen-inactivation treatment of blood components.blood transfusion provides an ideal portal of entry for microorganisms. although current residual risks of microbial infection by transfusion are extremely low in the developed world, the requirements for even safer blood are paradoxically increasing. such requirements are partly a legacy of the tragic transmissions of human immunodeficiency virus (hiv) by blood early in the acquired immunodeficiency syndrome pandemic and are legally expressed in consumer protection laws imposing strict product ...200415615254
aids, multicentric castleman's disease, and plasmablastic leukemia: report of a long-term survival.plasmablastic leukemia (pl) as a complication of human herpes virus 8 (hhv8)-associated castleman's disease is marked by a rapid and fatal outcome. in patients with aids, survival of 7 to 14 days after diagnosis has been reported. prompt splenectomy and chemotherapy might lead to a significant survival benefit. here we report a case of long-term survival in a patient with aids and multicentric castleman's disease (mcd) complicated by pl.200415624895
risk of transmission of herpesviruses through cord blood transplantation.cord blood (cb) progenitor cells are increasingly used for transplantation in children because of the lower risk of graft-versus-host disease compared with unrelated bone marrow and comparable rates of disease-free survival. there is concern that cb might carry a higher risk of opportunistic infections. human herpesviruses (hhv) are common pathogens in transplant recipients. cb donors are routinely tested for the presence of anti-cytomegalovirus (cmv) immunoglobulin m to reduce the risk of colle ...200515625542
therapeutic response of hiv-1 subtype c in african patients coinfected with either mycobacterium tuberculosis or human herpesvirus-8.a potential confounding factor in the treatment of human immunodeficiency virus (hiv) infection in africa is the frequent occurrence of opportunistic infections (ois). oi-induced immune activation can interfere with hiv-1 clearance by increasing viral replication and target cell availability.200415633090
development of a real-time qpcr assay for the detection of rv2 lineage-specific rhadinoviruses in macaques and baboons.two distinct lineages of rhadinoviruses related to kaposi's sarcoma-associated herpesvirus (kshv/hhv8) have been identified in macaques and other old world non-human primates. we have developed a real-time quantitative pcr (qpcr) assay using a taqman probe to differentially detect and quantitate members of the rhadinovirus-2 (rv2) lineage. pcr primers were derived from sequences within orf 60 and the adjacent orf 59/60 intergenic region which were highly conserved between the macaque rv2 rhadino ...200515634356
lymphadenopathy, pneumonia, and hiv--a common trio, an uncommon outcome. 200515652610
hhv-8/kshv during the development of kaposi's sarcoma: evaluation by polymerase chain reaction and immunohistochemistry.the human gamma-herpes virus-8 (hhv-8) was first described in aids-related kaposi's sarcoma (ks) tumour samples. in this study, we report comparative studies on paraffin-embedded biopsies of aids-related ks (aks) and endemic ks (eks) with regard to hhv-8 content as evaluated using polymerase chain reaction (pcr) and immunohistochemistry. dna was extracted either using chelex-100 or using qia-gene kit and was evaluated with the help of a semiquantitative pcr assay. the pcr detection of hhv-8 was ...200515660651
the proteasome inhibitor bortezomib (ps-341) inhibits growth and induces apoptosis in primary effusion lymphoma cells.the ubiquitin-proteasome pathway is responsible for degrading many critical regulatory proteins involved in immune and inflammatory responses, control of cell growth and apoptosis. recently, proteasome inhibitors have emerged as promising new therapeutic agents in hematological malignancies. here we show that bortezomib (ps-341), a proteasome-inhibitor, inhibits cellular proliferation and induces apoptosis in cell lines derived from primary effusion lymphoma (pel), a subtype of non-hodgkin's lym ...200515662128
the n-terminal peptide of the kaposi's sarcoma-associated herpesvirus (kshv)-cyclin determines substrate specificity.cyclin-dependent kinases (cdks) are activated by cyclin binding and phosphorylation by the cdk-activating kinase (cak). activation of cdk6 by the d-type cyclins requires phosphorylation of cdk6 by cak on threonine 177. in contrast, cdk6 is activated by the kaposi's sarcoma-associated herpesvirus (kshv)-cyclin in the absence and presence of cak phosphorylation. the activity of cdk6.kshv-cyclin complexes was investigated here by analyzing mutants of the kshv-cyclin and cdk6 in vitro as well as in ...200515664993
modulation of human herpesvirus 8/kaposi's sarcoma-associated herpesvirus replication and transcription activator transactivation by interferon regulatory factor 7.human herpesvirus 8 (hhv-8)/kaposi's sarcoma-associated herpesvirus infection goes through lytic and latent phases that are regulated by viral gene products, but very little is known about the involvement of host proteins. the replication and transcription activator (rta) is a viral protein sufficient to initiate lytic replication by activating downstream genes, including the viral early gene open reading frame 57 (orf 57), which codes for a posttranscriptional activator. in this study, we demon ...200515681443
increased efficiency of phorbol ester-induced lytic reactivation of kaposi's sarcoma-associated herpesvirus during s phase.expression of kaposi's sarcoma-associated herpesvirus (kshv) lytic genes is thought to be essential for the establishment and progression of kshv-induced diseases. the inefficiency of lytic reactivation in various in vitro systems hampers the study of lytic genes in the context of whole virus. we report here increased expression of kshv lytic genes and increased release of progeny virus when synchronized cultures of body cavity-based lymphoma-1 cells are treated with a phorbol ester during s pha ...200515681463
kaposi's sarcoma-associated herpesvirus/human herpesvirus type 8-positive solid lymphomas: a tissue-based variant of primary effusion lymphoma.kaposi's sarcoma-associated herpesvirus (kshv), also termed human herpesvirus type 8, is consistently identified in kaposi's sarcoma, primary effusion lymphoma (pel), and multicentric castleman's disease. here we report four cases of kshv-bearing solid lymphomas that occurred in aids patients (cases 1 to 3) and in a human immunodeficiency virus (hiv)-seronegative person (case 4). the patients presented extranodal masses in the abdomen (cases 1, 3, and 4) or skin (case 2), and nodal involvement, ...200515681470
endoscopic resection for the diagnosis of visceral kaposi's sarcoma.kaposi's sarcoma is an uncommon neoplasm that occasionally involves the gastrointestinal tract in immunosuppressed individuals. infection with human herpes virus 8 is known to be necessary for developing all forms of kaposi's sarcoma. we report a renal transplant recipient who developed visceral kaposi's sarcoma 18 months after the transplantation. in oriental countries, the incidence of kaposi's sarcoma is extremely low, and this is the first case of kaposi's sarcoma arising from a transplant r ...200515692796
confirming shedding of human herpesvirus 8 in urine from infected patients in brazil. 200515695733
the latency-associated nuclear antigen of rhesus monkey rhadinovirus inhibits viral replication through repression of orf50/rta transcriptional activation.rhesus monkey rhadinovirus (rrv) is a gamma-2-herpesvirus that is closely related to kaposi's sarcoma-associated herpesvirus/human herpesvirus-8. we have previously reported that the transcript for rrv latency-associated nuclear antigen (r-lana) is expressed during lytic replication in rhesus fibroblasts. in this article, we report the development of a latent culture system for rrv and show that mrna specific for r-lana is expressed during latency as well. we have characterized the r-lana protei ...200515709032
inter- and intra-person cytomegalovirus infection in malawian families.sequence polymorphisms in the gn and go genes of cytomegalovirus (cmv) amplified from mouth rinse and urine samples of 19 malawian patients with kaposi's sarcoma (ks) and 58 of their first-degree relatives were investigated. cmv-dna was amplified from 41 people (53%) from either the gn or go region in at least one sample, from 14 people (18%) in both domains in at least one sample, and from 13 (17%) in either domain in both samples. twenty-one (51%) were seropositive for human immunodeficiency v ...200515714485
the herpesvirus saimiri rta gene autostimulates via binding to a non-consensus response element.herpesvirus saimiri orf 50a protein expression is sufficient to reactivate the entire lytic-replication cycle. orf 50a functions as a sequence-specific transactivator that is capable of activating delayed-early gene expression via direct binding to an orf 50 response element (re) within the respective promoter. here, it is shown that orf 50a is capable of transactivating its own promoter. deletion analysis of the orf 50a promoter showed that the orf 50-responsive element is contained within an 8 ...200515722517
viral turn-on for kaposi's sarcoma cytokines. 200515759360
licking latency with licorice.numerous viruses cause latent infections in humans, and reactivation often results in pain and suffering. while vaccines for several of these viruses are available or currently being studied in clinical trials, and antiviral therapies have been successful in preventing or treating active infection, therapy to eradicate latent infection has lagged behind. a new study reported in this issue of the jci shows that treatment of cells latently infected with kaposi sarcoma-associated herpesvirus (kshv) ...200515765143
lymphangioma-like kaposi sarcoma.lymphangioma-like kaposi's sarcoma (llks) is a rare morphologic expression of kaposi's sarcoma (ks) that occurs in virtually all of the well-recognized clinical subtypes of the disease and has the potential to mimic other pathologic processes. in this study, we present the clinical and pathological features of four patients with llks.200515769278
identification of micrornas of the herpesvirus family.epstein-barr virus (ebv or hhv4), a member of the human herpesvirus (hhv) family, has recently been shown to encode micrornas (mirnas). in contrast to most eukaryotic mirnas, these viral mirnas do not have close homologs in other viral genomes or in the genome of the human host. to identify other mirna genes in pathogenic viruses, we combined a new mirna gene prediction method with small-rna cloning from several virus-infected cell types. we cloned ten mirnas in the kaposi sarcoma-associated vir ...200515782219
seroprevalence of human herpesvirus 8 infection in children born to hiv-1-infected women in são paulo, brazil.human herpesvirus-8 (hhv-8) appears to be transmitted mainly by sexual contact. however, several studies suggest that in developing countries the infection may be acquired early in life by routes other than sexual transmission. the present study estimated the seroprevalence of hhv-8 in brazilian children born to hiv-1-infected mothers. the serum samples were collected in a cross-sectional cohort study from 99 children born to hiv-infected mothers (median age 3.27 years; range 1.5-13.8 years) att ...200515785835
low seroprevalence of human herpesvirus 8 infection in croatia. 200515791527
activation of cd21 and cd23 gene expression by kaposi's sarcoma-associated herpesvirus rta.epstein-barr virus (ebv) ebna2 and kaposi's sarcoma-associated herpesvirus (kshv) replication and transcription activator (rta) are recruited to their responsive elements through interaction with a notch-mediated transcription factor, rbp-jkappa. in particular, rta and ebna2 interactions with rbp-jkappa are essential for the lytic replication of kshv and expression of b-cell activation markers cd21 and cd23a, respectively. here, we demonstrate that like ebv ebna2, kshv rta strongly induces cd21 ...200515795251
murine gammaherpesvirus 68 open reading frame 45 plays an essential role during the immediate-early phase of viral replication.murine gammaherpesvirus 68 (mhv-68) has been developed as a model for the human gammaherpesviruses epstein-barr virus and human herpesvirus 8/kaposi's sarcoma-associated herpesvirus (hhv-8/kshv), which are associated with several types of human diseases. open reading frame 45 (orf45) is conserved among the members of the gammaherpesvirinae subfamily and has been suggested to be a virion tegument protein. the repression of orf45 expression by small interfering rnas inhibits mhv-68 viral replicati ...200515795297
kaposi's sarcoma-associated herpesvirus expresses an array of viral micrornas in latently infected cells.micrornas (mirnas) are an endogenously encoded class of small rnas that have been proposed to function as key posttranscriptional regulators of gene expression in a range of eukaryotic species, including humans. the small size of mirna precursors makes them potentially ideal for use by viruses as inhibitors of host cell defense pathways. here, we demonstrate that the pathogenic human herpesvirus kaposi's sarcoma-associated herpesvirus (kshv) encodes an array of 11 distinct mirnas, all of which a ...200515800047
the aetiology and management of castleman disease at 50 years: translating pathophysiology to patient care.fifty years ago, dr benjamin castleman first described the unusual lymphoproliferative disorder that now bears his name. over the subsequent decades, astute clinical and pathologic observations coupled with clever molecular biologic research have increased our understanding of the aetiology of castleman disease (cd). this article proposes three broad cd variants based on both distinctive histopathology and clinical behaviour. the pivotal roles of infection with human herpesvirus 8 and interleuki ...200515801951
human herpesvirus-8: what (not) to do? 200515819663
identification of functional domains in kaposica, the complement control protein homolog of kaposi's sarcoma-associated herpesvirus (human herpesvirus 8).recently it has been shown that kaposica, an immune evasion protein of kaposi's sarcoma-associated herpesvirus, inactivates complement by acting on c3-convertases by accelerating their decay as well as by acting as a cofactor in factor i-mediated inactivation of their subunits c3b and c4b. here, we have mapped the functional domains of kaposica. we show that scrs 1 and 2 (scrs 1-2) and 1-4 are essential for the classical and alternative pathway c3-convertase decay-accelerating activity (daa), re ...200515827200
hhv-8-associated t-cell lymphoma in a lymph node with concurrent peritoneal effusion in an hiv-positive man.primary effusion lymphoma (pel) is an uncommon large cell lymphoma, usually seen in human immunodeficiency virus (hiv)-infected patients. pel is characterized by various clinical, histomorphologic, and immunophenotypical features, and is associated with the human herpes virus 8 (hhv-8). pel may present as either a body cavity-based lymphomatous effusion or a solid tumor mass. most so-called "solid pel" usually have an extranodal location; exceptionally rarely, they occur in lymph nodes. the majo ...200515832089
reversal of some viral il-6 electrostatic properties compared to il-6 contributes to a loss of alpha receptor component recruitment.human interleukin-6 (hil-6) is a pleiotropic mediator of activation and proliferation across a large number of different cell types. human herpesvirus-8 (hhv-8) has been associated with classical and aids-related kaposi's sarcoma (ks). hhv-8 encodes viral il-6 (vil-6), a functional homolog of human interleukin-6, that promotes the growth of ks and of some lymphoma cells. signaling induced by human il-6 requires recruitment of the glycoprotein gp130, which acts as the signal transducing chain, an ...200515861391
kaposi's sarcoma-associated herpesvirus activation of vascular endothelial growth factor receptor 3 alters endothelial function and enhances infection.kaposi's sarcoma-associated herpesvirus (kshv; also known as human herpesvirus 8) is the etiologic agent of kaposi's sarcoma, an endothelial neoplasm. this gamma-herpesvirus encodes for several unique proteins that alter target cell function, including the virion envelope-associated glycoprotein b (gb). glycoprotein b has an rgd (arg-gly-asp) motif at the extracellular amino terminus region and binds to the alpha3beta1 surface integrin, which enhances virus entry. we now report that gb can activ ...200515878864
[interaction of viruses with cellular response to hypoxia].recent studies show that low oxygen tension levels in cell culture up-regulate the replication of human b19 parvovirus, kaposi's sarcoma, and human immunodeficiency viruses as well as the expression of viral oncogenic proteins. the mechanisms of this regulation proceed with the major hypoxia-related factor, hif-1 (hypoxia inducible factor-1). hif-1 misregulation is implicated in the oncogenesis potential of some of these viruses.200515885203
investigation of the multimerization region of the kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) protein k-bzip: the proposed leucine zipper region encodes a multimerization domain with an unusual structure.the k8 gene of kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) shares many functional similarities with the bzlf1 gene of epstein-barr virus. the protein products of k8 and bzlf1, k-bzip (rap, k8) and zta (bzlf1, zebra, z) have both been proposed to be members of the bzip family of transcription factors, forming multimers via a coiled-coil motif termed a leucine zipper. substantial evidence supporting this model for zta is published. here, we demonstrate that the proposed leucine z ...200515919946
murine herpesvirus pathogenesis: a model for the analysis of molecular mechanisms of human gamma herpesvirus infections.murine herpes virus (mhv), a natural pathogen originally isolated from free-living rodents, constitutes the most amenable animal model for human gamma herpesviruses. based on dna sequence homology, this virus was classified as murid herpesvirus 4 to subfamily gammaherpesvirinae. pilot studies in our laboratory, using mice inoculated by the intranasal route, showed that mhv infects macrophages, b lymphocytes, lung alveolar as well as endothelial cells. from the lungs the virus spreads via the blo ...200515957234
novel cellular genes essential for transformation of endothelial cells by kaposi's sarcoma-associated herpesvirus.kaposi's sarcoma-associated herpesvirus (kshv) is involved in the development of lymphoproliferative diseases and kaposi's sarcoma. the oncogenicity of this virus is reflected in vitro by its ability to transform b cells and endothelial cells. infection of dermal microvascular endothelial cells (dmvec) transforms the cells from a cobblestone-like monolayer to foci-forming spindle cells. this transformation is accompanied by dramatic changes in the cellular transcriptome. known oncogenes, such as ...200515958552
aids-related malignancies: emerging challenges in the era of highly active antiretroviral therapy.human immunodeficiency virus (hiv)-infected patients are at increased risk of developing cancer, particularly in the later stages of acquired immune deficiency syndrome (aids). despite the advent of highly active anti-retroviral therapy (haart), malignancy in this population is a leading cause of morbidity and mortality. kaposi's sarcoma (ks) and aids-related non-hodgkin's lymphoma (arl) are the most common aids-defining malignancies. aids-related ks varies from minimal to fulminant disease. tre ...200515967835
molecular heterogeneity of sporadic adult burkitt-type leukemia/lymphoma as revealed by pcr and cytogenetics: correlation with morphology, immunology and clinical features.chromosomal translocations involving the myc oncogene are a hallmark of burkitt lymphoma but they are only found in a varying frequency in mature burkitt-type acute lymphoblastic leukemia (b-all). we have investigated samples of 56 sporadic burkitt leukemia/lymphoma patients for the translocations t(8;14)(q24;q32), t(2;8)(p11;q24) and t(8;22)(q24;q11). long pcr was used for detecting the immunoglobulin heavy chain (igh) translocation and cytogenetics and/or fluorescence in situ hybridization for ...200515973450
suppressive effect of human herpesvirus-8/kaposi sarcoma-associated herpesvirus on in vitro colony formation of hematopoietic progenitor cells. 200515978946
human herpesvirus-8-related kaposi's sarcoma after liver transplantation successfully treated with cidofovir and liposomal daunorubicin.the iatrogenic form of kaposi's sarcoma (ks) is typically observed among transplant recipients, and the most appropriate therapeutic approach (usually including reduction of immunosuppression, specific chemotherapy, and/or administration of antiviral agents against human herpes virus-8) is still controversial. available experiences on the effect of the anti-herpes viruses drug cidofovir provide conflicting results. herein, we report the clinical, histological, and virological features of a liver ...200515984947
human herpesvirus-8 seropositivity and clinical correlations in hiv-1-positive and highly exposed, persistently hiv-seronegative individuals in greece.the prevalence of anti-human herpesvirus 8 (hhv-8) antibodies was retrospectively assessed in a cohort of 248 consecutive hiv-1-positive patients followed up in an academic unit in greece during a 14-year period and in 46 highly exposed, persistently hiv-seronegative (heps) individuals. the impact of the initial anti-hhv-8 status on tumorgenesis and mortality was studied. the first available serum sample from the department's pool was tested. demographics and data regarding history of sexually t ...200515989433
human herpes virus 8 in hiv and non-hiv infected patients with pulmonary arterial hypertension in france. 200515990583
ubiquitination on nonlysine residues by a viral e3 ubiquitin ligase.ubiquitination controls a broad range of cellular functions. the last step of the ubiquitination pathway is regulated by enzyme type 3 (e3) ubiquitin ligases. e3 enzymes are responsible for substrate specificity and catalyze the formation of an isopeptide bond between a lysine residue of the substrate (or the n terminus of the substrate) and ubiquitin. mir1 and mir2 are two e3 ubiquitin ligases encoded by kaposi's sarcoma-associated herpesvirus that mediate the ubiquitination of major histocompa ...200515994556
[successful treatment with liposomal doxorubicin and foscarnet in a patient with widespread kaposi's sarcoma and human herpes virus 8-related, serious hemophagocytic syndrome, after renal transplantation].it is well known that the human herpes virus 8 (hhv8) is linked to several malignancies such as kaposi's sarcoma (ks). moreover, pancytopenia due to hemophagocytic syndrome could be associated with hhv8 infection. in renal transplant recipients affected by ks, the tapering of immunosuppression often leads to ks remission, but also results in graft loss in >50% of cases. chemotherapy and antiviral therapy have also been used, mainly in the presence of visceral involvement.200516001371
functional genomics and the development of pathogenesis-targeted therapies for kaposi's sarcoma.kaposi's sarcoma (ks) is a multifocal angioproliferative disorder affecting the skin, mucosa and viscera of individuals infected with human herpesvirus-8 (hhv-8; also kaposi's sarcoma-associated herpesvirus [kshv]). ks is the most common neoplasm in aids patients; the clinical outcome of aids-ks is significantly improved by highly active antiretroviral therapy (haart). however, in africa, where the severest manifestations of ks occur, there is limited access to these and other effective but expe ...200516013955
a relapsing inflammatory syndrome and active human herpesvirus 8 infection.we describe an immunocompetent 61-year-old woman who was negative for human immunodeficiency virus and who had recurrent human herpesvirus 8 (hhv-8) infection associated with a relapsing systemic inflammatory syndrome characterized by fever, lymphadenopathy, splenomegaly, edema, arthrosynovitis, and rash. kaposi's sarcoma developed 10 months after the initial clinical presentation. a correlation was documented between the recurrent clinical manifestations and the hhv-8 load in plasma and periphe ...200516014885
processivity factor of kshv contains a nuclear localization signal and binding domains for transporting viral dna polymerase into the nucleus.kaposi's sarcoma-associated human herpesvirus (kshv) encodes a processivity factor (pf-8, orf59) that forms homodimers and binds to viral dna polymerase (pol-8, orf9). pf-8 is essential for stabilizing pol-8 on template dna so that pol-8 can incorporate nucleotides continuously. here, the intracellular interaction of these two viral proteins was examined by confocal immunofluorescence microscopy. when individually expressed, pf-8 was observed exclusively in the nucleus, whereas pol-8 was found o ...200516043206
downregulation of the major histocompatibility complex class i molecules by human herpesvirus type 8 and impaired natural killer cell activity in primary effusion lymphoma development.primary effusion lymphomas (pels) are invariably infected by human herpesvirus type 8 (hhv8) and often co-infected by epstein-barr virus (ebv). we found that expression of major histocompatibility complex class i (mhc-i) surface molecules was significantly decreased in pel cells when compared with hhv8 negative lymphomas, irrespective of ebv infection. mhc-i downregulation rendered pel cells sensitive to recognition and killing by natural killer (nk) cells. intriguingly, analysis of mhc-i non-re ...200516044583
immunohistochemical and molecular assessment of human herpesvirus type 8 in gastrointestinal tumours.gastrointestinal stromal tumours (gists) are the most common mesenchymal tumours of the gastrointestinal tract, histologically identified as highly cellular spindle or epithelioid cell tumours, and often positive for cd34 (60-70%). kaposi's sarcomas (kss) are similar to gists: they are most often found in the gastrointestinal tract (although cutaneous lesions do occur), they are also composed of spindle or epithelioid cells (although erythrocytes are also seen), and the tumour cells are nearly a ...200516049289
hhv-8 and ebv are not commonly found in idiopathic pulmonary fibrosis.idiopathic pulmonary fibrosis/usual interstitial pneumonia (ipf/uip) is a diffuse and progressive lung disease whose pathogenesis is incompletely understood. recently, the presence of herpesvirus-specific dna was detected in the large majority of cases of a series of ipf/uip and other lung interstitial diseases. we have therefore tested our own ipf/uip series for the presence of hhv-8 and ebv proteins.200516053027
epigenetic mechanisms do not control viral latency iii in primary effusion lymphoma cells infected with a recombinant epstein-barr virus. 200516079894
linking kshv to human cancer.kaposi's sarcoma-associated herpesvirus (kshv), also known as human herpesvirus 8 (hhv-8), has been linked to several malignancies in humans. kshv is the etiologic agent associated with the development of kaposi's sarcoma (ks), primary effusion lymphoma (pel), and multicentric castleman's disease (mcd). kshv is a double-stranded dna virus that has been classified as a gammaherpesvirus. here, we review the association of kshv with human cancer, viral genes that may potentially be involved in the ...200516091195
targeting human herpesvirus-8 for treatment of kaposi's sarcoma and primary effusion lymphoma.human herpesvirus-8, also called the kaposi's sarcoma herpesvirus, is present in all cases of kaposi's sarcoma and primary effusion lymphoma and in some cases of multicentric castleman's disease. this review discusses mechanisms by which human herpesvirus-8 contributes to tumorigenesis and how this knowledge can be used to target the virus for the treatment of these tumors.200516093794
epidemiology and clinical characteristics of classic kaposi's sarcoma, seroprevalence, and variants of human herpesvirus 8 in south america: a critical review of an old disease.to review the current south american literature on classic kaposi's sarcoma (ks) and human herpesvirus 8 (hhv-8), and point the way for studies that still need to be performed.200516095940
increasing seroprevalence of human herpesvirus 8 (hhv-8) with age confirms hhv-8 endemicity in amazon amerindians from brazil.human herpesvirus 8 (hhv-8) seroprevalences were determined in two isolated amazon amerindian tribes, according to age, gender and familial aggregation. plasma and serum samples obtained from 982 amazon amerindians (664 tiriyó and 318 waiampi) were tested for antibodies against lytic and latent hhv-8 antigens by using 'in-house' immunofluorescence assays. overall, hhv-8 seroprevalence was 56.8 % (57.4 % in the tiriyó tribe and 55.7 % in the waiampi tribe). seroprevalence was independent of gende ...200516099900
envelope glycoprotein gb of kaposi's sarcoma-associated herpesvirus is essential for egress from infected cells.kaposi's sarcoma-associated herpesvirus (kshv) envelope glycoprotein gb interacts with cell surface heparan sulfate (hs) and alpha3beta1 integrin and plays roles in the initial binding and entry into the target cells and in the induction of preexisting host cell signal pathways. to define gb function further, using a bacterial artificial chromosome (bac) system carrying the kshv genome (bac36wt-kshv), we constructed a recombinant virus genome with the gb open reading frame (orf) deleted by repla ...200516103147
constitutive nf-kappab activation, normal fas-induced apoptosis, and increased incidence of lymphoma in human herpes virus 8 k13 transgenic mice.human herpesvirus 8 (hhv-8, also called kaposi's sarcoma-associated herpes virus) has been linked to kaposi's sarcoma and primary effusion lymphoma. hhv-8-encoded viral fas-associated death domain-like il-1-converting enzyme inhibitory protein (vflip) is one of the few viral proteins to be expressed in latently infected cells and plays a key role in the survival and proliferation of primary effusion lymphoma cells. two main functions have been ascribed to hhv-8 vflip, inhibition of caspase 8/fas ...200516120683
t- and b-cell clonality and frequency of human herpes viruses-6, -8 and epstein barr virus in angioimmunoblastic t-cell lymphoma.angioimmunoblastic t-cell lymphoma (t-ail) is a peripheral t-cell lymphoma of unknown etiology. previous clonality studies have shown a heterogeneous composition of this disease with varying restrictions of b- and t-cell populations in the tumour. for the first time in a single study and in the same pathological materials, we have analysed, lymphoid cell clonality and occurrence of human herpes viruses and epstein barr virus. of 18 cases 12 (66.6%) had clonal t- and three (16.6%) had clonal b-ce ...200416134192
crystal structure of viral macrophage inflammatory protein i encoded by kaposi's sarcoma-associated herpesvirus at 1.7a.viral macrophage inflammatory protein i (vmip-i) is a chemokine encoded by the kaposi's sarcoma-associated herpesvirus (kshv) that selectively activates the cc chemokine receptor 8 (ccr8), for which the endogenous ligand is ccl1. the crystal structure of vmip-i was determined at 1.7a for comparison with other chemokines, especially those that bind ccr8, such as vmip-ii from kshv, a ccr8 antagonist and the closest homolog (40% identical). vmip-i has a typical chemokine fold consisting of an exten ...200516140327
human herpesvirus 8 serological markers and viral load in patients with aids-associated kaposi's sarcoma in central african republic.epidemic kaposi's sarcoma (ks) is one of the most frequent types of cancer in several african countries; however, very few data are available on human herpesvirus 8 (hhv-8) markers in ks patients from central africa. in a series of 36 aids-ks cases from central african republic, we showed, using a real-time pcr quantitative assay, the high frequency (82%) of detectable hhv-8 dna in peripheral blood mononuclear cells (pbmcs). we also found that the level of antibodies directed against lytic or la ...200516145154
prevalence of some herpesviruses in gingival crevicular fluid.the herpesviruses, ancient pathogens which have co-evoluted with human, are etiologically associated with a number of diseases, from asymptomatic to oncogenic and mortal diseases. it seems that some of them have also an important role in the pathogenesis of human periodontal disease.200516157267
kshv viral cyclin inactivates p27kip1 through ser10 and thr187 phosphorylation in proliferating primary effusion lymphomas.kaposi sarcoma herpesvirus (kshv) infection is consistently associated with primary effusion lymphomas (pels) that are non-hodgkin lymphomas of b-cell origin. all pel cells are latently infected with kshv and express latent viral proteins such as the viral cyclin (v-cyclin), which has previously been implicated in down-regulation of cell-cycle inhibitor p27(kip1) levels via phosphorylation on thr187. pel cells retain high levels of p27(kip1) but yet proliferate actively, which has left the biolo ...200616160006
down-regulation of basophil function by human cd200 and human herpesvirus-8 cd200.human and rodent cd200 are recognized by the inhibitory cd200r, and these molecules play an important role in the regulation of the immune system. several viruses, such as human herpesvirus-6 (hhv-6), hhv-7, and hhv-8, possess a cd200 homologue, suggesting that these viruses regulate the immune response via cd200r. in this study, we analyzed the effect of human cd200 and the viral cd200 homologues on human cd200r-expressing cells. we found that human cd200r is predominantly expressed on basophil ...200516177086
kshv/hhv-8 associated lymph node based lymphomas in hiv seronegative subjects. report of two cases with anaplastic large cell morphology and plasmablastic immunophenotype.kaposi sarcoma associated herpesvirus (kshv)/human herpesvirus 8 (hhv-8) associated lymphomas, which often develop in human immunodeficiency virus (hiv) infected patients with advanced aids, present predominantly as primary effusion lymphoma (pel) or, less frequently, as "solid" extracavitary based lymphomas, associated with serous effusions. these last lymphomas, also called "solid pel", have been reported before the development of an effusion lymphoma and after resolution of pel. interestingly ...200516189148
an unusual case of posttransplant peritoneal primary effusion lymphoma with t-cell phenotype in a hiv-negative female, not associated with hhv-8.primary effusion lymphoma (pel) is a recently individualized form of non-hodgkin's lymphoma (who classification) that mainly develops in hiv infected males, more frequently in homosexuals and advanced stages of the disease (total cd4+ lymphocyte count below 100-200/microl). occasionally, it appears in other immunodepressive states (such as solid organs transplant period) and even, although very rarely, in immunocompetent patients. from a pathogenetic point of view, pel has been related to kaposi ...200516195773
immune mechanisms in murine gammaherpesvirus-68 infection.the murine gamma-herpesvirus-68 (mhv-68) is a relative of the kaposi's sarcoma-associated herpesvirus (kshv) and epstein-barr virus (ebv) that infects mice. all these gamma-herpesviruses are subject to immune control, but limit the impact of this control through immune evasion. molecular evasion mechanisms have been described in abundance. however, we can only speculate what ebv and kshv immune evasion contributes to the viral lifecycle. with mhv-68, we can analyze in vivo the contribution of im ...200516212523
the herpesvirus saimiri replication and transcription activator acts synergistically with ccaat enhancer binding protein alpha to activate the dna polymerase promoter.the open reading frame (orf) 50 gene product, also known as the replication and transcription activator (rta), is an immediate-early gene which is well conserved among all gamma-2 herpesviruses and plays a pivotal role in regulating the latent-lytic switch. herpesvirus saimiri (hvs) orf 50a functions as a sequence-specific transactivator capable of activating delayed-early (de) gene expression via binding directly to an orf 50 response element (re) within the respective promoter. analysis of the ...200516227275
brd2/ring3 interacts with a chromatin-binding domain in the kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 (lana-1) that is required for multiple functions of lana-1.latency-associated nuclear antigen 1 (lana-1) of kaposi's sarcoma-associated herpesvirus (kshv) mediates the episomal replication of the kshv genome, as well as transcriptional regulation, in latently infected cells. interaction of lana-1 with cellular chromatin is required for both these functions. an n-terminal heterochromatin-binding site in lana-1 is essential for the replication and maintenance of latent episomes, as well as transcriptional regulation. we have recently described a c-termina ...200516227282
human herpesvirus 8 and pulmonary hypertension.human herpesvirus 8 (hhv-8) antibodies were detected in 1 of 33 patients with pulmonary hypertension (including in 1 of 16 with idiopathic pulmonary arterial hypertension), 5 of 29 with cystic fibrosis, and 3 of 13 with interstitial lung disease. no relationship between hhv-8 infection and pulmonary hypertension was found.200516229789
human herpesvirus 8 infection in patients with cutaneous lymphoproliferative diseases.to investigate the prevalence of human herpesvirus 8 (hhv-8; kaposi sarcoma-associated herpesvirus) infection in patients with lymphoproliferative skin diseases such as large-plaque parapsoriasis (lpp) and mycosis fungoides compared with inflammatory cutaneous conditions or healthy control subjects.200516230560
extracavitary primary effusion lymphoma of the anorectum.we report a case of an extracavitary primary effusion lymphoma occurring in the anorectum of a patient with advanced acquired immune deficiency syndrome. the morphology, null cell immunophenotype, and acquisition of plasma cell markers in this case are typical of the so-called solid variant of primary effusion lymphoma. lymphoma cells in this case were shown to be co-infected with human herpesvirus-8 and epstein-barr virus. following combination chemotherapy and highly active antiretroviral ther ...200516231856
induced structure of a helical switch as a mechanism to regulate enzymatic activity.herpesviruses encode a protease that is activated by homodimerization at high enzyme concentrations during lytic replication. the homodimer contains two active sites, which are distal from the dimer interface. assignment of backbone nmr resonances and engineering of a redox switch show that two helices position a loop containing catalytic residues within each active site.200516244665
transcripts encoding k12, v-flip, v-cyclin, and the microrna cluster of kaposi's sarcoma-associated herpesvirus originate from a common promoter.kaposi's sarcoma-associated herpesvirus (kshv) is the causative agent of three malignancies associated with aids and immunosuppression. tumor cells harbor latent virus and express kaposin (open reading frame [orf] k12), v-flip (orf 71), v-cyclin (orf 72), and latency-associated nuclear antigen (lana; orf 73). orfs 71 to 73 are transcribed as multicistronic rnas initiating from adjacent constitutive and inducible promoters upstream of orf 73. here we characterize a third promoter embedded within ...200516254382
[kaposi's sarcoma].in recent years large amounts of findings have accumulated about kaposi's sarcoma, a virus induced angioproliferative disorder appearing in four clinical forms: classical, epidemic, endemic and iatrogenic, as it has been in focus of not only from the dermatologic but also from the viral tumorgenesis perspective. the common characteristics are the histopathological appearance, the causative role of the human herpesvirus 8 and the similar clinical picture (bluish-red macules, papules, and nodes). ...200516259333
reversibility of pulmonary arterial hypertension in hiv/hhv8-associated castleman's disease.the present study describes a case of pulmonary arterial hypertension (pah) associated with multicentric castleman's disease in a patient infected with hiv type 1 and human herpes virus 8. therapy included highly active antiretroviral therapy, warfarin, diuretics, continuous i.v. epoprostenol and 12-monthly pulses of cyclophosphamide. the patient's condition improved dramatically with complete reversibility of pah, allowing weaning of continuous i.v. epoprostenol therapy. after 5 yrs, both castl ...200516264059
gamma-herpesvirus neoplasia: a growing role for cox-2.both human gamma-herpesviruses, epstein-barr virus (ebv) and kaposi's sarcoma-associated herpesvirus (kshv) induce neoplasia. burkitt's and hodgkin's lymphomas harbor ebv sequences, while kshv has been associated with kaposi's sarcoma (ks), primary effusion lymphoma (pel), and multicentric castleman's disease (mcd). each of these gamma-herpesvirus-associated malignancies displays typical characteristics of neoplasia, such as angiogenesis and cell survival. one enzyme commonly overexpressed in br ...200516276519
multiplex pcr-based dna array for simultaneous detection of three human herpesviruses, evb, cmv and kshv.human lymphotropic herpesviruses, epstein-barr virus (ebv), cytomegalovirus (cmv) and kaposi's sarcoma-associated herpesvirus (kshv) are responsible for a wide variety of human diseases. due to an increase in diseased states associated with immunosuppression, more instances of co-morbid infections with these herpesviruses have resulted in viral reactivations that have caused numerous fatalities. therefore, the development of rapid and accurate method to detect these viruses in immunocompromised ...200616298362
kaposi's sarcoma-associated herpesvirus induction of ap-1 and interleukin 6 during primary infection mediated by multiple mitogen-activated protein kinase pathways.kaposi's sarcoma is an angioproliferative disseminated tumor of endothelial cells linked to infection with kaposi's sarcoma-associated herpesvirus (kshv). ap-1 transcription factors are involved in diverse biological processes, including infection and replication of viruses, cell growth, oncogenesis, angiogenesis, and invasion of cancer cells. here we show that kshv activates ap-1 during primary infection. the activation of ap-1 at the early stage of kshv infection is mainly mediated by virus en ...200516306573
the kshv oncoprotein vflip contains a traf-interacting motif and requires traf2 and traf3 for signalling.primary effusion lymphomas (pels) characterized by infection with the kaposi's sarcoma herpesvirus (kshv; also called human herpesvirus 8) depend on the expression of the viral fadd-like interleukin-1-beta-converting enzyme (flice)/caspase-8-inhibitory protein (vflip) for their survival. this effect is achieved by activation of the transcription factor nuclear factor-kappab (nf-kappab). tumour necrosis factor (tnf) receptor-associated factors (trafs) are direct mediators of nf-kappab signalling ...200616311516
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