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re: schulz, the pleiotropic effects of kaposi's sarcoma herpesvirus. j pathol 2006;208:187-198. 200717152082
downregulation of gamma interferon receptor 1 by kaposi's sarcoma-associated herpesvirus k3 and k5.upon viral infection, the major defense mounted by the host immune system is activation of the interferon (ifn)-mediated antiviral pathway. in order to complete their life cycles, viruses must modulate the host ifn-mediated immune response. the k3 and k5 proteins of a human tumor-inducing herpesvirus, kaposi's sarcoma-associated herpesvirus (kshv), have been shown to downregulate the surface expression of host immune modulatory receptors by increasing their endocytosis rates, which leads to supp ...200717166914
hhv-8 encoded lana-1 alters the higher organization of the cell nucleus.the latency-associated nuclear antigen (lana-1) of human herpes virus 8 (hhv-8), alternatively called kaposi sarcoma herpes virus (kshv) is constitutively expressed in all hhv-8 infected cells. lana-1 accumulates in well-defined foci that co-localize with the viral episomes. we have previously shown that these foci are tightly associated with the borders of heterochromatin 1. we have also shown that exogenously expressed lana-1 causes an extensive re-organization of hoechst 33248 dna staining pa ...200717433107
immune evasion by kaposi's sarcoma-associated herpesvirus.to efficiently establish a persistent infection, kaposi's sarcoma-associated herpesvirus (kshv; also known as hhv8) dedicates a large amount of its coding potential to produce proteins that antagonize the immune system of its host. these viral immunomodulators interfere with both the innate and adaptive immune responses and most of them are homologous to cellular proteins, suggesting that they have been pirated from the host during viral evolution. in this review, i present recent advances in th ...200717457345
chemokines as mediators of angiogenesis.chemokines were originally described as cytokines that mediate leukocyte recruitment to sites of inflammation. members of a subgroup of chemokines, the cxc family, also play a critical role in both physiologic and pathologic angiogenesis, including in the context of chronic inflammation, fibrosis, and malignancy. a unique feature of this family of cytokines is that, on the basis of their structure and receptor binding, individual ligands display either angiogenic or angiostatic biological activi ...200717479186
functional characterization of the m-type k15-encoded membrane protein of kaposi's sarcoma-associated herpesvirus.kaposi's sarcoma-associated herpesvirus (kshv) or human herpesvirus 8 is the causative agent of kaposi's sarcoma, primary effusion lymphoma and the plasma-cell variant of multicentric castleman's disease. its alternatively spliced k15 gene encodes several membrane proteins with varying numbers of transmembrane domains. two highly diverged alleles of the k15 gene, termed predominant (p) and minor (m), exist and share only 33 % amino acid identity with one another, but retain conserved putative sr ...200717485529
non-hodgkin lymphomas concurrent with hhv8-associated kaposi's sarcoma in the same lymph node in aids and non-aids patients.the association between lymphomas and kaposi's sarcoma has been described since 1920. the simultaneous presence of the 2 pathologic entities within the same lymph node is a rare and interesting occurrence. in the few cases described, the presence of human herpesvirus 8 (hhv8) and epstein-barr virus (ebv) in the different neoplastic areas was investigated only by immunohistochemistry and in situ hybridization studies.200717505129
lipid rafts of primary endothelial cells are essential for kaposi's sarcoma-associated herpesvirus/human herpesvirus 8-induced phosphatidylinositol 3-kinase and rhoa-gtpases critical for microtubule dynamics and nuclear delivery of viral dna but dispensable for binding and entry.early during de novo infection of human microvascular dermal endothelial (hmvec-d) cells, kaposi's sarcoma-associated herpesvirus (kshv) (human herpesvirus 8 [hhv-8]) induces the host cell's preexisting fak, src, phosphatidylinositol 3-kinase (pi3-k), rho-gtpases, diaphanous-2 (dia-2), ezrin, protein kinase c-zeta, extracellular signal-regulated kinase 1/2 (erk1/2), and nf-kappab signal pathways that are critical for virus entry, nuclear delivery of viral dna, and initiation of viral gene expres ...200717507466
seroprevalence of human herpes virus-8 in renal transplant recipients: a single center study from iran.the long-term risk of malignancy among renal transplant patients is approximately 100 times that of the general population. unlike north america and many european countries, kaposi's sarcoma is the most common cancer after renal transplantation in most series reported from the middle east. human herpes virus-8 (hhv-8) has a major role in the pathogenesis of kaposi's sarcoma. the risk of posttransplantation kaposi's sarcoma is 23% to 28% among seropositive patients compared with 0.7% among serone ...200717524874
concomitant and fatal hhv-8+ multicentric castleman's disease and kaposi's sarcoma in the same lymph node of an hiv- liver transplant patient. 200717543090
ps-341 or a combination of arsenic trioxide and interferon-alpha inhibit growth and induce caspase-dependent apoptosis in kshv/hhv-8-infected primary effusion lymphoma cells.kaposi's sarcoma (ks)-associated herpes virus (kshv) is the causative agent of primary effusion lymphoma and of ks. primary effusion lymphoma (pel) is an aggressive proliferation of b cells. conventional chemotherapy has limited benefits in pel patients, and the prognosis is very poor. we previously reported that treatment of human t-cell leukemia virus type 1 (htlv-1)-associated adult t-cell leukemia/lymphoma cells either with arsenic trioxide (as) combined to interferon-alpha (ifn-alpha) or wi ...200717568816
transmission of human herpesvirus 8 by blood transfusion. 200717202462
human herpesvirus 8 and iron staining are useful in differentiating kaposi sarcoma from interstitial granuloma annulare.we studied 20 granuloma annulare (ga) cases (10 interstitial and 10 palisaded) and 19 kaposi sarcoma (ks) cases (9 "early" and 10 typical). tissue sections were stained for iron, hale colloidal iron, human herpesvirus 8 (hhv-8), cd31, cd34, cd68, collagen iv, factor xiiia, and mib-1. iron staining of dermal tissue associated with the lesion was confirmed in all ks cases and no ga cases. immunohistochemical stains for hhv-8 were positive in all 9 cases of early ks and most cases (9/10) of typical ...200717210517
construction of an infectious rhesus rhadinovirus bacterial artificial chromosome for the analysis of kaposi's sarcoma-associated herpesvirus-related disease development.rhesus rhadinovirus (rrv) is closely related to kaposi's sarcoma-associated herpesvirus (kshv)/human herpesvirus 8 (hhv-8) and causes kshv-like diseases in immunocompromised rhesus macaques (rm) that resemble kshv-associated diseases including multicentric castleman's disease and non-hodgkin's lymphoma. rrv retains a majority of open reading frames (orfs) postulated to be involved in the pathogenesis of kshv and is the closest available animal model to kshv infection in humans. here we describe ...200717215283
human herpesvirus-8 in peruvian blood donors: a population with hyperendemic disease?serum samples from 128 blood donors were tested for antibodies specific for human herpesvirus-8 by an immunofluorescence assay that detects antibodies against mainly lytic antigens. an overall seroprevalence of 56.25% was found (male donors, 54.68%; female donors, 57.11%). these findings indicate that human herpesvirus-8 infection is hyperendemic in peruvian blood donors.200717243060
high conservation of kaposi sarcoma--associated herpesvirus micrornas implies important function. 200717262700
conservation of virally encoded micrornas in kaposi sarcoma--associated herpesvirus in primary effusion lymphoma cell lines and in patients with kaposi sarcoma or multicentric castleman disease.micrornas are small noncoding rnas that posttranscriptionally regulate gene expression. kaposi sarcoma (ks)-associated herpesvirus (kshv) encodes 12 distinct microrna genes, all of which are located within the latency-associated region that is highly expressed in all kshv-associated malignancies.200717262705
concurrent cmv and ebv dnaemia is significantly correlated with a delay in the response to haart in treatment-naive hiv type 1-positive patients.the purpose of this study was to assess the qualitative single and multiple herpes virus dnaemia in the peripheral blood leukocytes (pbls) of hiv-1-positive patients and its impact on the response to highly active antiretroviral therapy (haart) and immune reconstitution. all (163) hiv-1-positive patients attending "syngros aids referral center" from november 2000 to february 2001 were recruited. cmv, hsv-1, hsv-2, ebv, and hhv-8 dna were detected in pbls by polymerase chain reaction (pcr). patie ...200717263627
herpesvirus saimiri episomal persistence is maintained via interaction between open reading frame 73 and the cellular chromosome-associated protein mecp2.herpesvirus saimiri (hvs) is the prototype gamma-2 herpesvirus, which naturally infects the squirrel monkey saimiri sciureus, causing an asymptomatic but persistent infection. the latent phase of gamma-2 herpesviruses is characterized by their ability to persist in a dividing cell population while expressing a limited subset of latency-associated genes. in hvs only three genes, open reading frame 71 (orf71), orf72, and orf73, are expressed from a polycistronic mrna. orf73 has been shown to be th ...200717267510
kshv/hhv-8 and hiv infection in kaposi's sarcoma development.kaposi's sarcoma (ks) is a highly and abnormally vascularized tumor-like lesion affecting the skin, lymphnodes and viscera, which develops from early inflammatory stages of patch/plaque to late, nodular tumors composed predominant of spindle cells (sc). these sc are infected with the kaposi's sarcoma-associated herpesvirus or human herpesvirus-8 (kshv/hhv-8). ks is promoted during hiv infection by various angiogenic and pro-inflammatory factors including hiv-tat. the latency associated nuclear a ...200717270056
kaposi's sarcoma-associated herpesvirus induces sustained nf-kappab activation during de novo infection of primary human dermal microvascular endothelial cells that is essential for viral gene expression.in vitro kaposi's sarcoma-associated herpesvirus (kshv) infection of primary human dermal microvascular endothelial (hmvec-d) cells and human foreskin fibroblast (hff) cells is characterized by the induction of preexisting host signal cascades, sustained expression of latency-associated genes, transient expression of a limited number of lytic genes, and induction of several cytokines, growth factors, and angiogenic factors. since nf-kappab is a key molecule involved in the regulation of several ...200717287275
kaposi's sarcoma-associated herpesvirus promotes angiogenesis by inducing angiopoietin-2 expression via ap-1 and ets1.infection by kaposi's sarcoma-associated herpesvirus (kshv) is required for the development of kaposi's sarcoma (ks), a highly inflammatory angiogenic tumor of endothelial cells commonly found in untreated aids patients. angiopoietin 2 (ang-2) modulates the vasculature during inflammation and angiogenesis, but the mechanism by which kshv regulates ang-2 expression has not been investigated. here, we show that kshv infection of primary human umbilical vein endothelial cells induced the expression ...200717287278
thymoma and immunodeficiency (good syndrome): a report of 2 unusual cases and review of the literature.good syndrome is a rare cause of combined b- and t-cell immunodeficiency that occurs in association with a thymoma. patients affected with good syndrome have increased susceptibility to bacterial, fungal, viral, and opportunistic infections.200717304889
kaposi's sarcoma-associated herpesvirus lana protein downregulates nuclear glycogen synthase kinase 3 activity and consequently blocks differentiation.the kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen (lana) protein interacts with glycogen synthase kinase 3 (gsk-3) and relocalizes gsk-3 in a manner that leads to stabilization of beta-catenin and upregulation of beta-catenin-responsive cell genes. the lana-gsk-3 interaction was further examined to determine whether there were additional downstream consequences. in the present study, the nuclear gsk-3 bound to lana in transfected cells and in bcbl1 primary effusion l ...200717314169
primary intraosseous kaposi's sarcoma presenting as an asymptomatic periapical radiolucency: a case report.kaposi's sarcoma (ks) is a common mucocutaneous manifestation of acquired immunodeficiency syndrome (aids). primary bone lesions have been reported but are rare. a 38-year-old african-american male who was human immunodeficiency virus (hiv)-positive appeared for the evaluation of an asymptomatic well-defined radiolucency of the mandibular midline discovered on routine radiographic examination. the adjacent central incisors were asymptomatic, nonmobile, and vital. the overlying mucosa and cortica ...200717317238
bone marrow findings in multicentric castleman disease in hiv-negative patients.because bone marrow histology in multicentric castleman disease in human immunodeficiency virus-negative patients is not well reported, we investigated sequential bone marrow biopsies of 3 affected human immunodeficiency virus-negative patients, of which one was human herpes virus 8 (hhv8)-positive. the histologic evaluation of the bone marrow revealed lymphoid follicles with regressed germinal centers in 1 patient. another patient showed tumorlike but bland polyclonal plasmacytosis with large p ...200717325481
fatal hemophagocytic syndrome related to active human herpesvirus-8/kaposi sarcoma-associated herpesvirus infection in human immunodeficiency virus-negative, non-transplant patients without related malignancies.hemophagocytic syndrome (hs) may occur as a consequence of herpes viral infections. human herpesvirus 8 (hhv-8)/kaposi sarcoma-associated herpesvirus has so far been recognized as a trigger of hs only in immunosuppressed subjects or in patients with kaposi sarcoma and/or hhv-8-related lymphoproliferative diseases. we report two italian human immunodeficiency virus (hiv)-negative elderly men who developed an hs with a rapidly fatal course, following treatment with corticosteroids for autoimmune h ...200717331129
kaposi's sarcoma in nigeria.the prevalence of kaposi's sarcoma (ks) in parts of africa has been on the increase as a result of the human immunodeficiency virus (hiv) infection pandemic. however, there is a paucity of information for nigeria.200717343581
human herpes virus 8 infection in kidney transplant patients from an area of northwestern italy (piemonte region).human herpes virus 8 (hhv-8) infection is associated with kaposi sarcoma (ks) and other neoplastic and non-neoplastic manifestations. a strong association between hhv-8 and ks has been evidenced in transplant recipients, particularly kidney recipients.200717353210
enhanced tumorigenicity of fibroblasts transformed with human herpesvirus 8 chemokine receptor vgpcr by successive passage in nude and immunocompetent mice.the human herpes virus 8 (hhv-8)-encoded g protein-coupled chemokine receptor (vgpcr) has been implicated in the pathogenesis of kaposi's sarcoma (ks), particularly because of its high constitutive signaling activity. here, we used retroviral transduction to generate vgpcr-expressing 3t3 fibroblasts that are tumorigenic in nude mice, but as expected fail to induce tumors in their immunocompetent counterparts. however, tumor fragments obtained from nude mice grow progressively in immunocompetent ...200717353903
establishment of a human herpes virus-8-negative malignant effusion lymphoma cell line (str-428) carrying concurrent translocations of bcl2 and c-myc genes.a new cell line, str-428 was established from ascites tumor cells of a malignant effusion lymphoma patient without human herpes virus-8 (hhv-8) infection. str-428 cells showed an immunophenotype of mature b-cells and produced few cytokines related to lymphomatous effusion. karyotypic and genetic analysis revealed complex translocations including t(14;18)(q32;q21) effecting igh/bcl2 and der(8)t(3;8)(q27;q24) involving c-myc. str-428 represents a unique, b-cell lymphoma cell line carrying concurre ...200717368758
kaposi's sarcoma and pemphigus. 200717374010
[kaposi's sarcoma treated with topical alitretinoin].kaposi's sarcoma is a multifocal neoplastic process with four clinical variants, all of them induced by human herpes virus 8. currently there is no treatment of choice and it depends on the extension and location of the lesions as well as on the clinical type of the disease. alitretinoin gel 0.1 % is approved for the treatment of cutaneous lesions of aids-associated kaposi's sarcoma. the majority of its side effects appear at the site of application and can lead to therapy withdrawal. we report ...200717374335
middle-aged man presenting with erythematous brownish plaques. diagnosis: kaposi's sarcoma (ks) as defining disease of acquired immunodeficiency syndrome (aids) by hiv-1 infection. 200717376210
epstein-barr virus inhibits kaposi's sarcoma-associated herpesvirus lytic replication in primary effusion lymphomas.the majority of aids-associated primary effusion lymphomas (pel) are latently infected with both kaposi's sarcoma-associated herpesvirus (kshv) and epstein-barr virus (ebv). pels harboring two viruses have higher oncogenic potential, suggesting functional interactions between ebv and kshv. the kshv replication and transcription activator (k-rta) is necessary and sufficient for induction of kshv lytic replication. ebv latent membrane protein 1 (lmp-1) is essential for ebv transformation and estab ...200717376914
systematic identification of cellular signals reactivating kaposi sarcoma-associated herpesvirus.the herpesvirus life cycle has two distinct phases: latency and lytic replication. the balance between these two phases is critical for viral pathogenesis. it is believed that cellular signals regulate the switch from latency to lytic replication. to systematically evaluate the cellular signals regulating this reactivation process in kaposi sarcoma-associated herpesvirus, the effects of 26,000 full-length cdna expression constructs on viral reactivation were individually assessed in primary effu ...200717397260
intestinal occlusion caused by rosai-dorfman disease mimicking colonic diverticulitis.rosai-dorfman disease (rdd) involves the gastrointestinal tract only in exceptional cases, and this very unusual site of presentation can confuse the pathologist. we present a case of rdd manifesting as an intestinal occlusion caused by colonic diverticulitis. the patient was a 79-year-old man with myelodysplasia, who presented with fever, abdominal pain, and constipation. colonoscopy revealed sigmoiditis and diverticulosis. microscopic study of the sigmoid colon surgical specimen showed the his ...200717400399
the kaposi's sarcoma-associated herpesvirus k5 e3 ubiquitin ligase modulates targets by multiple molecular mechanisms.kaposi's sarcoma-associated herpesvirus encodes two highly related membrane-associated, ring-ch-containing (march) family e3 ubiquitin ligases, k3 and k5, that can down regulate a variety of cell surface proteins through enhancement of their endocytosis and degradation. in this report we present data that while k5 modulation of major histocompatibility complex class i (mhc-i) closely mirrors the mechanisms used by k3, alternative molecular pathways are utilized by this e3 ligase in the down regu ...200717409151
kaposi's sarcoma-associated herpesvirus (kshv) oncoprotein k13 bypasses trafs and directly interacts with the ikappab kinase complex to selectively activate nf-kappab without jnk activation.kaposi's sarcoma herpesvirus oncoprotein vflip k13 is a potent activator of nf-kappab and plays a key role in viral pathogenesis. k13 contains a putative traf-interacting motif, which is reportedly required for its interaction with traf2. the k13-traf2 interaction is believed to be essential for the recruitment of k13 to the i-kappab kinase (ikk) complex and for k13-induced nf-kappab and jnk activation. in addition, traf3 has been reported to be required for k13-induced nf-kappab and jnk activat ...200717597077
persistent long-term human herpesvirus 6 (hhv-6) infection in a patient with langerhans cell histiocytosis.langerhans cell histiocytosis (eosinophilic granuloma) was first diagnosed in the adolescence of a male patient presented. several years later persisting human herpesvirus 6 (hhv-6) infection was recognized. the hhv-6 infection could be verified retrospectively in his historical histological samples; the continuous presence of hhv-6 could be established through 17 years of disease course. the patient was operated several times during this period for painful relapses, and developed diabetes insip ...200717607379
kaposi's sarcoma-associated herpesvirus orf57 protein enhances mrna accumulation independently of effects on nuclear rna export.the orf57 protein expressed by kaposi's sarcoma-associated herpesvirus (kshv) during lytic replication is essential for kshv virion production. orf57 enhances gene expression by increasing accumulation of target gene mrnas. orf57 interacts with the cellular export factor ref and with rna, suggesting that it may provide target mrnas with access to ref, which mediates nuclear rna export by binding to tap/nxf1. a mutational analysis of orf57 was performed to study the role of ref binding, rna inter ...200717609285
plasmablastic microlymphoma occurring in human herpesvirus 8 (hhv-8)-positive multicentric castleman's disease and featuring a follicular growth pattern.plasmablastic microlymphoma (pml) is defined as the accumulation of monotypic but polyclonal plasmablasts in lymphoid tissues involved in human herpes virus 8 (hhv-8)-positive multicentric castleman's disease (mcd). so far, the nature of this very rare condition remains poorly determined. in this study, we describe a human immunodeficiency virus (hiv)-seropositive patient who developed a pml in the setting of hhv-8-positive mcd. in contrast to the cases previously reported, most of the plasmabla ...200717614857
kaposi's sarcoma of the recto sigmoid colon in a patient with hiv infection and a high cd4 count.kaposi's sarcoma (ks) is a well-recognized, hiv-associated opportunistic tumour, which was first described in 1872 by a hungarian dermatologist, moritz kaposi. it predominantly affects homosexual men and heterosexual patients from africa infected with hiv. the lesions can arise anywhere in the body but occur more frequently on the skin. despite a trend towards lower cd4 counts at the time of ks presentation, the use of antiretroviral therapy has been associated with a reduction in mortality comp ...200717623511
latent human herpesvirus - 8 (hhv-8) infection in female commercial sex workers from imbituba, santa catarina, brazil.human herpesvirus 8 (hhv-8) infection was identified in 6 out of 90 (6.7%) female commercial sex workers from imbituba, santa catarina, and was associated to age. frequencies of 5.6% of anti-latent and 3.3% of anti-lytic antibodies were detected. considering non-endemic areas from brazil, the anti-latent antibodies frequency seems elevated and requires further investigation on referent female population.200717625718
analysis of viral cis elements conferring kaposi's sarcoma-associated herpesvirus episome partitioning and maintenance.maintenance of kaposi's sarcoma-associated herpesvirus (kshv) episomes in latently infected cells is dependent on the latency-associated nuclear antigen (lana). lana binds to the viral terminal repeats (tr), leading to recruitment of cellular origin recognition complex proteins. additionally, lana tethers episomes to chromosomes via interactions with histones h2a and h2b (a. j. barbera et al., science 311:856-861, 2006). despite these molecular details, less is known about how episomes are estab ...200717626102
oncogenic properties of hiv-tat in colorectal cancer cells.with the advent of highly-active-anti-retroviral-therapy (haart), hiv patients can expect to live beyond 10-15 years following diagnosis. an unexpected result of increased survival is the emergence of opportunistic, oncogenic virus-associated cancers such as burkitt's lymphoma (epstein-barr virus), cervical cancer (human papilloma virus) and kaposi's sarcoma (kaposi's sarcoma-associated herpesvirus) in this immuno-compromised population. furthermore, there are reports of colorectal cancers (crc) ...200717627503
kaposi's sarcoma herpesvirus load in biopsies of cutaneous and oral kaposi's sarcoma lesions.to evaluate human herpesvirus 8/kaposi's sarcoma associated herpesvirus (hhv-8/kshv) viral load in diagnostic, (formalin fixed, paraffinised) biopsies and patient serum during tumour progression of oral and cutaneous aids-related kaposi's sarcoma (aks), and endemic kaposi's sarcoma (eks) by a sensitive and specific quantitative real time polymerase chain reaction (qrt-pcr) assay.200717627810
tumor markers and treatments for kaposi sarcoma. 200717630560
immunosuppression-related fibroproliferative polyps of the tongue.polypoid tongue lesions arising after bone marrow transplantation have been described. their etiopathogenesis has been unclear, as has their relationship to similar lesions arising in other settings of chronic immunodeficiency. we identified 12 polypoid lesions (from 8 immunosuppressed patients aged 6 months to 13 years) among all tongue lesions biopsied over the course of 13 years at our institution. clinical history, histologic and ultrastructural features, special stains (gram, grocott methen ...200717638430
binding of kaposi's sarcoma-associated herpesvirus k-bzip to interferon-responsive factor 3 elements modulates antiviral gene expression.kaposi's sarcoma-associated herpesvirus encodes numerous regulatory proteins capable of modulating viral and cellular gene expression and affecting host cell functions. k-bzip, a leucine zipper-containing transcription factor encoded by orfk8, is one such protein. during infection, transcription of the orfk8 early gene is turned on by the immediate-early replication and transcription factor activator (rta). one described function of the k-bzip nuclear protein is to interact with and repress rta- ...200717652396
should cellular therapy products be tested for human herpesvirus 8? 200717655602
[contribution of immunohistochemical detection of human herpesvirus-8 latent nuclear antigen-1 in the diagnosis of kaposi disease].to study the immunohistochemical expression of hhv8 in kaposi's lesions and in other vascular lesions and to determine the utility of this technique in differentiating between kaposi's disease (kd) and other vascular lesions.200717665661
cannabinoid modulation of kaposi's sarcoma-associated herpesvirus infection and transformation.kaposi's sarcoma-associated herpesvirus (kshv; also named human herpesvirus 8) is necessary but not sufficient for the development of kaposi's sarcoma. a variety of factors may contribute to the pathogenesis of kaposi's sarcoma in addition to kshv. marijuana is a widely used recreational agent, and delta(9)-tetrahydrocannabinol (delta(9)-thc), the major active component of marijuana, is prescribed for medicinal use. to evaluate how cannabinoids may affect the pathogenesis of kaposi's sarcoma, we ...200717671191
human transcriptome subtraction by using short sequence tags to search for tumor viruses in conjunctival carcinoma.digital transcript subtraction (dts) was developed to subtract in silico known human sequences from expression library data sets, leaving candidate nonhuman sequences for further analysis. this approach requires precise discrimination between human and nonhuman cdna sequences. database comparisons show high likelihood that small viral sequences can be successfully distinguished from human sequences. dts analysis of 9,026 20-bp tags from an expression library of bcbl-1 cells infected with kaposi' ...200717686852
molecular piracy: manipulation of the ubiquitin system by kaposi's sarcoma-associated herpesvirus.ubiquitination, one of several post-translational protein modifications, plays a key role in the regulation of cellular events, including protein degradation, signal transduction, endocytosis, protein trafficking, apoptosis and immune responses. ubiquitin attachment at the lysine residue of cellular factors acts as a signal for endocytosis and rapid degradation by the 26s proteasome. it has recently been observed that viruses, especially oncogenic herpesviruses, utilise molecular piracy by encod ...200717688306
[update on kaposi's sarcoma].kaposi's sarcoma (ks) is a mesenchymal tumor involving blood and lymphatic vessels and induced by viral growth factors (hhv8-il6). this article reviews the epidemiology, pathogenesis, clinical spectrum (classic ks, iatrogenic immunosuppressive ks, endemic african ks, and aids-ks), histological features, staging criteria and treatment of ks. unlike industrialized countries that have benefited from widespread use of highly active antiretroviral therapy (haart), developing countries continue to hav ...200717691428
the k15 protein of kaposi's sarcoma-associated herpesvirus recruits the endocytic regulator intersectin 2 through a selective sh3 domain interaction.kaposi's sarcoma-associated herpesvirus, also known as human herpesvirus 8, is closely associated with several cancers including kaposi's sarcoma, primary effusion lymphoma, and multicentric castleman's disease. the rightmost end of the kshv genome encodes a protein, k15, with multiple membrane-spanning segments and an intracellular carboxy-terminal tail that contains several conserved motifs with the potential to recruit interaction domains (i.e., sh2, sh3, traf) of host cell proteins. k15 has ...200717696407
development of a fluorescence-based assay to screen antiviral drugs against kaposi's sarcoma associated herpesvirus.tumors associated with kaposi's sarcoma-associated herpesvirus infection include kaposi's sarcoma, primary effusion lymphoma, and multicentric castleman's disease. virtually all of the tumor cells in these cancers are latently infected and dependent on the virus for survival. latent viral proteins maintain the viral genome and are required for tumorigenesis. current prevention and treatment strategies are limited because they fail to specifically target the latent form of the virus, which can pe ...200717699731
human herpesvirus-8 infection and oral shedding in amerindian and non-amerindian populations in the brazilian amazon region.human herpesvirus type 8 (hhv-8) is hyperendemic in amerindian populations, but its modes of transmission are unknown.200717703414
seroreactivity to kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) latent nuclear antigen in aids-associated kaposi's sarcoma patients depends on cd4+ t-cell count.in aids/kaposi's sarcoma (ks) patients, the sensitivity of immunofluorescence assays for detecting antibodies against latent nuclear antigen ranges from 52% to 93%. however, in classic and african ks, sensitivities above 90% have been reported systematically. this study evaluates whether cd4+ t-cell count affects seroreactivity to kshv lana and to lytic antigens in aids/ks patients. kaposi's sarcoma-associated herpesvirus (kshv) latent (ifa-lana) and lytic (ifa-lytic and orf65/k8.1 eia) antibodi ...200717705173
hhv-8+, ebv+ multicentric plasmablastic microlymphoma in an hiv+ man: the spectrum of hhv-8+ lymphoproliferative disorders expands.human herpesvirus-8 (hhv-8) is associated with several distinct lymphoproliferative disorders: primary effusion lymphoma, multicentric castleman disease (mcd), mcd-associated plasmablastic lymphoma and hhv-8+, epstein-barr virus (ebv)+ germinotropic lymphoproliferative disorder. we report the case of a human immunodeficiency virus (hiv)+ male with fever, generalized lymphadenopathy, and splenomegaly. two peripheral lymph nodes were excised and showed features of mcd and a prominent proliferation ...200717721201
intestinal kaposi's sarcoma may mimic gastrointestinal stromal tumor in hiv infection.diffuse intestinal kaposi's sarcoma shares macroscopic and histopathologic features with gastrointestinal stromal tumors. correct diagnosis may pose a clinical challenge. we describe the case of a young hiv-1-infected african lady without advanced immunodeficiency, who presented with a diffuse spindle cell tumor of the gut. initial diagnosis was of a gastrointestinal stromal tumor, based on endoscopy and histopathology. further evaluation revealed evidence for human herpesvirus 8 (hhv8) and the ...200717724811
some malignant tumours in hiv -infected individuals in benin city nigeria.the aim of the study was to report the cases of some malignancies seen in human immune deficiency virus (hiv) - positive patients seen at the ubth between january 1999 and december 2003.200717767201
multicentric castleman disease: use of hhv8 viral load monitoring and positron emission tomography during follow-up. 200717786732
human herpesvirus 8 (hhv-8) inhibits monocyte differentiation into dendritic cells and impairs their immunostimulatory activity.several viruses interfere with the host immune response by infecting dendritic cells and by altering their functional activity. here, we report that exposure to human herpesvirus 8 (hhv-8) of human dendritic cell (dc) monocyte precursors resulted in impaired immature dc (idc) formation as indicated by a reduced cd1a expression. in accordance, the immunostimulatory ability of such idc was significantly reduced, as indicated by mixed lymphocyte culture (mlr) assays. the immunostimulatory functions ...200717822781
the galpha12/13 family of heterotrimeric g proteins and the small gtpase rhoa link the kaposi sarcoma-associated herpes virus g protein-coupled receptor to heme oxygenase-1 expression and tumorigenesis.heme oxygenase-1 (ho-1), an inducible enzyme that metabolizes the heme group, is highly expressed in human kaposi sarcoma lesions. its expression is up-regulated by the g protein-coupled receptor from the kaposi sarcoma-associated herpes virus (vgpcr). although recent evidence shows that ho-1 contributes to vgpcr-induced tumorigenesis and vascular endothelial growth factor (vegf) expression, the molecular steps that link vgpcr to ho-1 remain unknown. here we show that vgpcr induces ho-1 expressi ...200717881360
first report of kaposi's sarcoma-associated herpesvirus dna sequences from cuban kaposi's sarcoma patients without hiv infection. 200717885307
synergistic activation of interferon-beta gene transcription by the viral flice inhibitory protein of kaposi's sarcoma-associated herpesvirus and type i ifn activators.expression of kaposi's sarcoma-associated herpesvirus v-flip leads to the spindle-shape morphology of endothelial cells and is essential for the survival of primary effusion lymphoma cells. activation of the nf-kappab transcription factor by v-flip is responsible for these effects. considering that the interferon-beta (ifn-beta) gene is regulated partly through nf-kappab, we sought to determine whether v-flip would activate the expression of the ifn-beta gene. our results indicate that when v-fl ...200717899551
identification of b cell epitopes at the c-terminus of latency-associated nuclear protein of the kaposi's sarcoma-associated herpesvirus.the latency-associated nuclear antigen (lana) of kaposi's sarcoma-associated herpesvirus (kshv) plays a key role in the induction of cell transformation, maintenance of viral episome, and modulation of immune response in human. to identify the presence of b cell epitopes within c-terminus of lana and to characterize the monoclonal antibodies (mabs) against this protein, we expressed the c-terminal region at aa 794-1000 of lana (plana-c) in escherichia coli as a fusion protein. kshv-positive huma ...200717900217
kaposi's sarcoma herpesvirus-encoded latency-associated nuclear antigen stabilizes intracellular activated notch by targeting the sel10 protein.deregulation of the evolutionarily conserved notch signaling is highly correlated with oncogenesis. intracellular activated notch (icn) is a protooncogene linked to the transcription activation of a number of cellular genes involved in cell cycle regulation, differentiation, and proliferation. stability of icn is tightly regulated by the sel10-mediated ubiquitin-proteasome pathway. sel10 can function as a negative regulator of notch and exhibits activities of a tumor-suppressor protein. this art ...200717909182
rna editing of the human herpesvirus 8 kaposin transcript eliminates its transforming activity and is induced during lytic replication.human herpesvirus 8 is the etiologic agent associated with kaposi's sarcoma and primary effusion lymphoma (pel). the k12 rna, which produces as many as three variants of the kaposin protein, as well as a microrna, is the most abundant transcript expressed in latent kaposi's sarcoma-associated herpesvirus infection, and yet it is also induced during lytic replication. the portion of the transcript that includes the microrna and the kaposin a sequence has been shown to have tumorigenic potential. ...200717913828
aids defining lymphomas in the era of highly active antiretroviral therapy (haart): an african perspective.the intermediate to high grade b-cell non-hodgkin lymphomas are now one of three malignant aids defining conditions. the others being kaposi's sarcoma and cervical carcinoma. while co-infection with oncogenic agents including the human herpes 8 or epstein-barr virus offer targets in preventive treatment strategies for these aids defining lymphomas (adl), administration of highly active antiretroviral therapy leading to immune reconstitution permits use of standard or even high-dose cytotoxic dru ...200717931978
reactivation of kaposi's sarcoma-associated herpesvirus by natural products from kaposi's sarcoma endemic regions.kaposi's sarcoma (ks) and its causative agent, kaposi's sarcoma associated herpesvirus (kshv/hhv-8), a gamma2 herpesvirus, have distinctive geographical distributions that are largely unexplained. we propose the "oncoweed" hypothesis to explain these differences, namely that environmental cofactors present in ks endemic regions cause frequent reactivation of kshv in infected subjects, leading to increased viral shedding and transmission leading to increased prevalence of kshv infection as well a ...200717066452
a dynamic model for induced reactivation of latent virus.we develop a deterministic mathematical model to describe reactivation of latent virus by chemical inducers. this model is applied to the reactivation of latent kshv in bcbl-1 cell cultures with butyrate as the inducing agent. parameters for the model are first estimated from known properties of the exponentially growing, uninduced cell cultures. additional parameters that are necessary to describe induction are determined from fits to experimental data from the literature. our initial model pro ...200717045614
kaposi sarcoma herpesvirus-encoded vflip and virf1 regulate antigen presentation in lymphatic endothelial cells.kaposi sarcoma-associated herpesvirus (kshv) is etiologically linked to kaposi sarcoma (ks), a tumor genetically akin to lymphatic endothelial cells (lecs). we obtained the immune transcriptional signature of ks and used kshv-infected lecs (klecs) as an in vitro model to determine the effects of kshv on transcription and expression of genes involved in immunity. the antigen presentation, interferon (ifn) response, and cytokine transcriptomes of klecs resemble those of ks. transcription of genes ...200717047149
modulation of host gene expression by the k15 protein of kaposi's sarcoma-associated herpesvirus.kaposi's sarcoma-associated herpesvirus (kshv) contains several open reading frames (orfs) encoding proteins capable of initiating signal transduction pathways. among them is the k15 orf, which consists of eight exons encoding a protein with 12 predicted transmembrane domains and a cytoplasmic c terminus. when transiently expressed, the 8-exon k15 transcript gives rise to a protein with an apparent molecular mass of 45 kda. k15 interacts with cellular proteins, traf (tumor necrosis factor recept ...200717050609
dna viruses in human cancer: an integrated overview on fundamental mechanisms of viral carcinogenesis.the first experimental data suggesting that neoplasm development in animals might be influenced by infectious agents were published in the early 1900s. however, conclusive evidence that dna viruses play a role in the pathogenesis of some human cancers only emerged in the 1950s, when epstein-barr virus (ebv) was discovered within burkitt lymphoma cells. besides ebv, other dna viruses consistently associated with human cancers are the hepatitis b virus (hbv), human papillomavirus (hpv), and kaposi ...200716814460
opposing roles of rna receptors tlr3 and rig-i in the inflammatory response to double-stranded rna in a kaposi's sarcoma cell line.kaposi's sarcoma (ks) is strongly associated with ks herpes virus infection, and inflammation plays an important role in this disease. we have shown that human ks biopsy-derived slk cells, which are of endothelial origin and form ks-like tumors in nude mice, express the viral rna pattern recognition receptors toll-like receptor 3 (tlr3), retinoic acid-inducible gene-i (rig-i), and melanoma-differentiation-associated gene 5 (mda5). furthermore, slk cells have enhanced release of il-6, il-8 (cxcl8 ...200718155685
multicentric castleman disease, kaposi sarcoma, hemophagocytic syndrome, and a novel hhv8-lymphoproliferative disorder.the case of a 45-year-old man with hiv disease with bulky lymphadenopathy, fevers, and weight loss is presented. immune reconstitution inflammatory syndrome was initially believed to be the cause, but the patient was found to suffer from kaposi sarcoma, multicentric castleman disease, hemophagocytic syndrome, and a newly described lymphoproliferative disorder. the diagnostic reasoning related to the causes of the fulminant illness is discussed as well as the roles of epstein-barr virus, human he ...200718178978
ebv detection in hiv-related oral plasmablastic lymphoma.plasmablastic lymphoma (pbl) of the oral cavity is an aggressive neoplasm derived from b cell, considered to be the second more common among human immunodeficiency virus (hiv)-associated malignancies. as epstein-barr virus (ebv) infection has been associated with this neoplasm, the aim of the present study was to assess the presence of ebv in 11 cases of oral hiv-related pbl and investigate the controversial issue of the presence of human herpesvirus-8 (hhv-8) in these tumors.200717944673
intravascular kaposi's sarcoma - a hitherto unrecognized phenomenon.based on the spectrum of histological features, kaposi's sarcoma (ks) is grouped into patch, plaque and nodular stages. the histological changes overlap, especially with lesional evolution. to date, intravascular ks is undocumented.200717944727
hiv-associated kaposi sarcoma: pathogenesis and therapy.while classical kaposi sarcoma is a slowly progressing tumor, aids-related kaposi sarcoma is much more aggressive. after introduction of antiretroviral therapy and with the use of well- tolerated chemotherapeutic agents, complete remission of the tumor can be achieved. local therapeutic options include excision, cryosurgery, radiation and alitretinoin gel. in 45 % of patients with more than 400/microl cd4+ lymphocytes, interferon-alpha induces complete remission. new concepts of pathogenesis lea ...200717944950
antibodies against kaposi sarcoma-associated herpes virus (kshv) complement control protein (kcp) in infected individuals.kaposi sarcoma-associated herpesvirus (kshv) is the most important etiopathological factor of kaposi's sarcoma (ks) and some specific types of malignant lymphomas. one of the viral lytic genes encodes the kshv complement control protein (kcp), which functionally mimics human complement inhibitors. although this protein provides an advantage for evading the complement attack, it can serve as target for adaptive immune response. herein, we identified anti-kcp igg antibodies in patients with ks and ...200717964697
hiv-associated oral kaposi sarcoma and hhv-8: a review.kaposi sarcoma is the most common malignant tumour associated with hiv infection. in the majority of cases oral tissues are involved and in 22% the initial presentation is in the oral cavity. the oral lesions are either single or multifocal, and the palate, gingiva and tongue are the sites most frequently involved. the pathogenesis of kaposi sarcoma in hiv-seropositive subjects is complex. it involves interaction between human herpesvirus-8 (hhv-8) and hiv, altered cellular signal transduction p ...200717987883
hiv-associated kaposi sarcoma and gender.cancer in individuals living with hiv and aids is a common source of morbidity and mortality, especially in the underdeveloped world. as antiretrovirals are distributed with greater equity across the globe, individuals with hiv and aids are living longer and developing malignancies, as opposed to other opportunistic infections.200718022592
hiv infection and lymphoma.the incidence of lymphoma in patients with hiv infection greatly exceeds that of the general population. the increased risk for lymphoma appears related to multiple factors, including the transforming properties of the retrovirus itself, the immunosuppression and cytokine dysregulation that results from the disease, and, most importantly, opportunistic infections with other lymphotrophic herpes viruses such as epstein-barr virus and human herpesvirus 8. histologically lymphomas fall into three g ...200718042692
kaposi's sarcoma in hiv-infected patients: when and how should we evaluate bone involvement? 200718090056
reactivation and lytic replication of kshvherpesviruses are extremely successful pathogens that have coevolved with their mammalian hosts over the past 60–80 million years (mcgeoch and davison, 1999). this success likely is attributable to the ability of the herpesviridae to establish lifelong latent infections of their host. latently infected cells provide a perpetual reservoir from which progeny viruses can be amplified for dissemination within the host and transmission between hosts. herpesvirologists have traditi ...200721348086
introduction to the human γ-herpesvirusesthis chapter will provide a brief background into the γ-herpesviruses family in comparison to other members of the herpesvirus family; but the primary focus of this chapter will be to recount the discovery of the two human γ-herpesviruses (ebv and kshv) and the diseases associated with infection of each virus, a brief introduction into their life cycles, and finally a description of the genome characteristics of the viruses including a description of their respective geno ...200721348088
human gammaherpesvirus immune evasion strategiesthe human γ-hvs are able to establish a lifelong, persistent infection that is largely clinically inapparent within the immunocompetent host. however, when these viruses are not kept in check, a variety of lymphoproliferative and neoplastic disorders result that will be detailed elsewhere within this volume. in brief, for hhv-8, also known as kaposi’s sarcoma-associated herpesvirus (kshv), these neoplasias include kaposi’s sarcoma (ks), multicentric castleman’s disease (m ...200721348105
kshv-transformed primary effusion lymphoma cells induce a vegf-dependent angiogenesis and establish functional gap junctions with endothelial cells.kaposi's sarcoma-associated herpesvirus (kshv) is the causative agent of primary effusion lymphoma (pel) and of kaposi's sarcoma. pel is an aggressive proliferation of b cells with poor prognosis. we evaluated both in vitro and in vivo the potential role of angiogenic factors secreted by pel cells, that is, their interaction with endothelial cells and their implication in the invasive behavior of tumoral cells. in vitro, pel-induced angiogenesis is dependent on vascular endothelial growth factor ...200818094712
unique structures in a tumor herpesvirus revealed by cryo-electron tomography and microscopy.gammaherpesviruses, including the human pathogens epstein-barr virus and kaposi's sarcoma-associated herpesvirus, are causative agents of lymphomas and other malignancies. the structural characterization of these viruses has been limited due to difficulties in obtaining adequate amount of virion particles. here we report the first three-dimensional structural characterization of a whole gammaherpesvirus virion by an emerging integrated approach of cryo-electron tomography combined with single-pa ...200818096403
intracellular localization map of human herpesvirus 8 proteins.human herpesvirus 8 (hhv-8) is the etiological agent of kaposi's sarcoma. we present a localization map of 85 hhv-8-encoded proteins in mammalian cells. viral open reading frames were cloned with a myc tag in expression plasmids, confirmed by full-length sequencing, and expressed in hela cells. protein localizations were analyzed by immunofluorescence microscopy. fifty-one percent of all proteins were localized in the cytoplasm, 22% were in the nucleus, and 27% were found in both compartments. s ...200818077714
kaposi's sarcoma after liver transplantation from a donor with a history of ventriculoperitoneal shunt and craniotomy for primary central nervous system lymphoma: report of a case.the transplantation of organs from donors who have undergone shunt surgery or craniotomy for a malignant central nervous system (cns) tumor is controversial. we report a case of kaposi's sarcoma (ks) developing as a result of immunosuppression in the recipient of a liver transplant from a donor who underwent craniotomy and ventriculoperitoneal shunt surgery for primary cns lymphoma. polymerase chain reaction assay did not isolate human herpes virus-8 in the kaposi lesions. to our knowledge, this ...200818085374
prevalence and correlates of human herpesvirus 8 infection among peruvian men who have sex with men.infection with human herpesvirus 8 (hhv-8) is common among men who have sex with men (msm) in north america and europe and is also found to be endemic in some regions of south america. little is known about hhv-8 prevalence and its correlates among msm in the andean region.200818989224
[diagnostic image (381). a man with painful, red spots on one foot].a 49-year-old turkish man with classic kaposi sarcoma on his right foot, was successfully treated by irradiation.200818998270
cd8+ t cell immunity to epstein-barr virus and kaposi's sarcoma-associated herpes virus.gammaherpesviruses are agents which have evolved to persist within the lymphoid system and many have oncogenic potential; studying gammaherpesvirus infections therefore has the potential to reveal much about the workings of the immune system and the control over viral oncogenesis. the lymphocryptovirus epstein-barr virus (ebv) and the rhadinovirus kaposi's sarcoma-associated herpesvirus (kshv, also known as human herpesvirus 8) are the two human gammaherpesviruses. analysis of the t cell respons ...200819007888
integrin alphavbeta3 binds to the rgd motif of glycoprotein b of kaposi's sarcoma-associated herpesvirus and functions as an rgd-dependent entry receptor.kaposi's sarcoma-associated herpesvirus (kshv) envelope-associated glycoprotein b (gb) is involved in the initial steps of binding to host cells during kshv infection. gb contains an rgd motif reported to bind the integrin alpha(3)beta(1) during virus entry. although the ligand specificity of alpha(3)beta(1) has been controversial, current literature indicates that alpha(3)beta(1) ligand recognition is independent of rgd. we compared alpha(3)beta(1) to the rgd-binding integrin, alpha(v)beta(3), ...200818045938
multicentric castleman disease is associated with polyfunctional effector memory hhv-8-specific cd8+ t cells.multicentric castleman disease (mcd) is a devastating human herpesvirus 8 (hhv-8)-related lymphoproliferative disorder that occurs in immunocompromised persons. to determine the role of immune responses in mcd, we studied the frequency, antigenic repertoire, differentiation, and functional profile of hhv-8-specific cd8(+) t cells in mcd patients and in human immunodeficiency virus-coinfected asymptomatic hhv-8 carriers (ac). screening cd8(+) t-cell responses with elispot interferon-gamma (ifn-ga ...200818000163
genotypic analysis on the orf-k1 gene of human herpesvirus 8 from patients with kaposi's sarcoma in xinjiang, china.human herpesvirus 8 (hhv-8) is thought to be essential for the development of all forms of kaposi's sarcoma (ks). hhv-8 dna is present virtually in all ks tumor biopsy samples. genes at both ends of the hhv-8 genome have been shown to vary considerably. seven major molecular subtypes of hhv-8 were defined based on the amino acid sequence of the open reading frame k1 (orf-k1), generally known as a, b, c, d, e, f, and z. most strains collected worldwide were clustered into two subtypes (a and c). ...200819022199
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