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down-regulation of nkg2d and nkp80 ligands by kaposi's sarcoma-associated herpesvirus k5 protects against nk cell cytotoxicity.natural killer (nk) cells are important early mediators of host immunity to viral infections. the nk activatory receptors nkg2d and nkp80, both c-type lectin-like homodimeric receptors, stimulate nk cell cytotoxicity toward target cells. like other herpesviruses, kaposi's sarcoma-associated herpesvirus (kshv) down-regulates mhc class i molecules to avoid detection by cytotoxic t lymphocytes but renders cells susceptible to nk cell cytotoxicity. we now show that the kshv immune evasion gene, k5, ...200818230726
transmission of kaposi sarcoma-associated herpesvirus in sub-saharan africa. 200818301068
contribution of viral and cellular cytokines to kaposi's sarcoma-associated herpesvirus pathogenesis.kaposi's sarcoma (ks)-associated herpesvirus is associated with the proliferative/malignant disorders ks, primary effusion lymphoma (pel), and multicentric castleman's disease (mcd) in patients with aids. in spite of recent advances in the treatment of ks, pel and mcd represent therapeutic challenges. recent advances in dissecting the pathogenesis of these diseases have indicated that the viral cytokine il-6 and the cellular cytokines/growth factors il-10, il-6, stromal cell-derived factor 1, an ...200818319288
detection of human herpesviruses hhv-6, hhv-7 and hhv-8 in whole blood by real-time pcr using the new cmv, hhv-6, 7, 8 r-gene kit.human herpesviruses 6 (hhv-6), 7 (hhv-7) and 8 (hhv-8) are lymphotropic herpesviruses that may cause opportunistic diseases in immunosuppressed patients such as transplant or aids patients. the new commercial cmv hhv-6, 7, 8 r-gene kit (argene, varilhes, france) for the simultaneous quantitation of hhv-6 and qualitative detection of hhv-7 and hhv-8 was evaluated using whole blood samples (respectively, n=175, 100 and 161) and using different extraction and real-time pcr platforms in two centers ...200818329730
images in hiv/aids. elephantiasis nostras verrucosa secondary to kaposi sarcoma: a rare case. 200818330034
bortezomib (ps-341) in patients with human herpesvirus 8-associated primary effusion lymphoma. 200818341641
differential regulation of the attachment of kaposi's sarcoma-associated herpesvirus (kshv)-infected human b cells to extracellular matrix by kshv-encoded gb and cellular alphav integrins.kaposi's sarcoma-associated herpesvirus (kshv) has two modes of replications: latent and lytic replications. reactivation from latency is dictated, in part, by the cell cycle. herein, we have attempted to delineate the importance of cell cycle in kshv pathogenesis by exploring the expression pattern of cell-surface receptors during different phases of the cell cycle. alphav integrin expression is augmented during s phase in fibroblasts, epithelial and kshv-infected cells. using a matrigel system ...200818363908
seroprevalence and risk factors for human herpesvirus 8 infection, rural egypt.to determine whether human herpesvirus 8 (hhv-8) is associated with schistosomal and hepatitis c virus infections in egypt, we surveyed 965 rural household participants who had been tested for hhv-8 and schistosomal infection (seroprevalence 14.2% and 68.6%, respectively, among those <15 years of age, and 24.2% and 72.8%, respectively, among those > or =15 years of age). among adults, hhv-8 seropositivity was associated with higher age, lower education, dental treatment, tattoos, > or =10 lifeti ...200818394276
genetic diversity of the kaposi's sarcoma herpesvirus k1 protein in aids-ks in zimbabwe.kaposi's sarcoma-associated herpesvirus (kshv) encodes genetically diverse k1 alleles which have unique geographic distributions. little is known about k1 genetic diversity in zimbabwe where acquired immunodeficiency syndrome-associated ks (aids-ks) is epidemic.200818394954
yuan chang and patrick moore: teaming up to hunt down cancer-causing viruses. 200818398088
use of multiplex pcr and real-time pcr to detect human herpes virus genome in ocular fluids of patients with uveitis.to measure the genomic dna of human herpes viruses (hhv) in the ocular fluids and to analyse the clinical relevance of hhv in uveitis.200818408082
lymph nodes involved by multicentric castleman disease among hiv-positive individuals are often involved by kaposi sarcoma.multicentric castleman disease (mcd), a lymphoproliferative disorder and kaposi sarcoma (ks), a vascular tumor, both occur at a higher frequency among patients with human immunodeficiency virus (hiv) infection. human herpes virus 8 (hhv8), with an ability to infect and persist in b-lymphoid cells and endothelial cells, is causally associated with both mcd and ks. the coexistence of these hhv8-associated diseases in the same tissue samples has hitherto not been investigated. in this report, we co ...200818469709
natural killer cell evasion by an e3 ubiquitin ligase from kaposi's sarcoma-associated herpesvirus.viruses exploit the ubiquitin system by targeting cell-surface receptors recognized by immune cells for internalization, thereby evading recognition. we have characterized the kshv (kaposi's sarcoma-associated herpesvirus)-encoded e3 ubiquitin ligases, k3 and k5. we find their activities not only prevent recognition by cytotoxic t-lymphocytes, but also promote evasion of nk (natural killer) cells. nk cells recognize and lyse virus-infected cells expressing ligands for activatory receptors such a ...200818481981
valganciclovir and human herpesvirus-8. 200818491975
kaposi's sarcoma and mtor: a crossroad between viral infection neoangiogenesis and immunosuppression.the incidence of kaposi's sarcoma (ks) among the recipients of solid organ transplants is about 500 times the rate in the general population, suggesting a role for immunosuppression in the development of the disease. the drugs used for the induction and maintenance of immunosuppression and the length of treatment with these agents influence both the incidence and the type of cancer development. the clinical presentation of ks in transplant recipients is often limited to the skin. the risk of dea ...200818498314
clinical implications of idiopathic multicentric castleman disease among japanese: a report of 28 cases.to clarify the clinicopathologic findings of idiopathic multicentric castleman disease among japanese, 28 cases were studied. two variants were delineated by the clinicopathologic findings (1) idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia (n = 18) and (2) nonidiopathic plasmacytic lymphadenopathy type (n= 10). clinicopathologically, idiopathic plasmacytic lymphadenopathy was defined by the prominent polyclonal hyperimmunoglobulinemia, normal germinal centers, and ...200818499694
development of an immunofluorescence assay using recombinant proteins expressed in insect cells to screen and confirm presence of human herpesvirus 8-specific antibodies.human herpesvirus 8 (hhv-8), or kaposi's sarcoma (ks)-associated herpesvirus, has been linked to all forms of ks. the results of most current serological assays for the detection of hhv-8-specific antibodies have low levels of concordance among themselves. to establish a sensitive and specific testing strategy that can be used to screen for hhv-8-specific antibodies, three hhv-8 proteins, orf65, orf73, and k8.1a, were expressed by using baculoviral vectors in insect cells and incorporated into a ...200818508931
predicting the evolution of kaposi sarcoma, in the highly active antiretroviral therapy era.the outcome of kaposi sarcoma varies. while many patients do well on highly active antiretroviral therapy, others have progressive disease and need chemotherapy. in order to predict which patients are at risk of unfavorable evolution, we established a prognostic score.200818520345
crystal structure of a vflip-ikkgamma complex: insights into viral activation of the ikk signalosome.key to the pathogenicity of several viruses is activation of the canonical nuclear factor-kappab (nf-kappab) transcriptional pathway. subversion of this tightly regulated mechanism is achieved through the production of host mimetic viral proteins that deregulate the transcription process. one such protein is ks-vflip (produced by the kaposi's sarcoma herpes virus [kshv]), which associates with ikkgamma, an essential component of the ikk complex or signalosome. this interaction renders the canoni ...200818538660
kaposi's sarcoma-associated herpesvirus confers a survival advantage to endothelial cells.kaposi's sarcoma-associated herpesvirus (kshv) is associated with three different human malignancies, including kaposi's sarcoma (ks), primary effusion lymphoma, and multicentric castleman's disease. the ks lesion is of endothelial cell in origin and is highly dependent on autocrine and paracrine factors for survival and growth. in this study, we show that kshv infection of endothelial cells induces the activation of the prosurvival phosphatidylinositol 3-kinase (pi3k)/akt/mammalian target of ra ...200818559509
human herpesvirus 8 infections in patients with immunodeficiencies.in 1994, chang et al described a novel herpesvirus in tissues from patients with kaposi sarcoma, referred to as kaposi sarcoma herpesvirus or human herpesvirus 8. they used a very sophisticated technique of molecular biology to isolate unknown dna sequences from kaposi sarcoma lesions, which were not present in normal tissues. it turned out that these sequences corresponded to a previously unrecognized gamma herpesvirus highly homologous to human herpesvirus 4 (epstein-barr virus) and to herpesv ...200818570975
activation of akt through gp130 receptor signaling is required for kaposi's sarcoma-associated herpesvirus-induced lymphatic reprogramming of endothelial cells.kaposi's sarcoma (ks) is the most common tumor of aids patients worldwide. ks-associated herpesvirus (kshv) is the infectious cause of this highly vascularized skin tumor. the main cell type found within a ks lesion, the spindle cell, is latently infected with kshv and has markers of both blood and lymphatic endothelial cells. during development, lymphatic endothelial cells differentiate from preexisting blood endothelial cells. interestingly, kshv infection of blood endothelial cells induces ly ...200818579585
editorial commentary: treatment of kaposi sarcoma in the highly active antiretroviral therapy era. 200818582204
primary microrna transcript retention at sites of transcription leads to enhanced microrna production.micrornas (mirnas) are noncoding rnas with important roles in regulating gene expression. in studying the earliest nuclear steps of mirna biogenesis, we observe that primary mirna (pri-mirna) transcripts retained at transcription sites due to the deletion of 3'-end processing signals are converted more efficiently into precursor mirnas (pre-mirnas) than pri-mirnas that are cleaved, polyadenylated, and released. flanking exons, which also increase retention at transcription sites, likewise contri ...200818625843
human herpesvirus type 8 in patients with cirrhosis: correlation with sex, alcoholism, hepatitis b virus, disease severity, and thrombocytopenia.immunologic abnormalities in patients with cirrhosis strongly correlate with severity of liver cirrhosis. the association between cirrhosis and human herpesvirus type 8 (hhv-8) infection is unclear. plasma samples were obtained from 74 healthy control subjects and 59 patients with cirrhosis. the seropositive rates for hhv-8 antibodies in patients with cirrhosis (25/59 [42%]) were significantly higher than that in healthy control subjects (18/74 [24%]; p = .027), particularly in men (p = .027), p ...200818628092
changes in t-cell responses against human herpesvirus-8 correlate with the disease course of iatrogenic kaposi's sarcoma in a patient with undifferentiated arthritis.to describe the first in-depth analysis of both the t-cell responses against human herpesvirus-8 (hhv-8) and the hhv-8 viral load in 1 patient who developed iatrogenic hhv-8-associated-kaposi's sarcoma (ks) following immunosuppressive treatment for undifferentiated arthritis and to review the literature on iatrogenic ks (iks).200918639317
the effects of human herpesvirus 8 infection and interferon-gamma response in cutaneous lesions of kaposi sarcoma differ among human immunodeficiency virus-infected and uninfected individuals.kaposi sarcoma (ks) is associated with human herpesvirus 8 (hhv-8). the cutaneous immune response in this tumour is not well established and a better understanding is necessary.200818644020
gender differences in hiv progression to aids and death in industrialized countries: slower disease progression following hiv seroconversion in women.to evaluate sex differences in human immunodeficiency virus (hiv) disease progression before (pre-1997) and after (1997-2006) introduction of highly active antiretroviral therapy, the authors used data from a collaboration of 23 hiv seroconverter cohort studies from europe, australia, and canada restricted to the 6,923 seroconverters infected through injecting drug use and sex between men and women. within a competing risk framework, they used cox proportional hazards models allowing for late en ...200818663213
human immunodeficiency virus and liver transplantation: our point of view.highly active antiretroviral therapy (haart) has been able to improve the immune system function and survival of hiv patients with a consequent increase in the number of hiv patients affected by end-stage liver disease (esld). between june 2003 and october 2006, 10 hiv-positive patients underwent liver transplantations in our center.200818675102
suppression of dendritic cell differentiation through cytokines released by primary effusion lymphoma cells.functional impairment of dendritic cells (dc) appears to be one of the mechanisms responsible for tumor escape from the control of the immune system. dc isolated from tumor-bearing animals and cancer patients with solid or with hematological malignancies have phenotypic and functional abnormalities. in addition, supernatants from in vitro cultured tumor cells have been shown to interfere with dc differentiation from cd34+ and monocyte precursors. primary effusion lymphoma (pel) is a human herpes ...200818680763
genetic disruption of kshv major latent nuclear antigen lana enhances viral lytic transcriptional program.following primary infection, kshv establishes a lifelong persistent latent infection in the host. the mechanism of kshv latency is not fully understood. the latent nuclear antigen (lana or lna) encoded by orf73 is one of a few viral genes expressed during kshv latency, and is consistently detected in all kshv-related malignancies. lana is essential for kshv episome persistence, and regulates the expression of viral lytic genes through epigenetic silencing, and inhibition of the expression and tr ...200818684478
kaposi's sarcoma-associated herpesvirus (kshv) rta and cellular hmgb1 proteins synergistically transactivate the kshv orf50 promoter.kaposi's sarcoma-associated herpesvirus 'replication transcriptional activator' (rta) plays a critical role in the switch from latency to lytic replication. rta upregulates several lytic kshv genes, including its own, through multiple mechanisms. we demonstrate that cellular hmgb1 binds and synergistically upregulates the orf50 promoter in conjunction with rta. no direct interaction between rta and hmgb1 was observed, however a ternary complex is formed in the presence of oct1. furthermore, dele ...200818692049
[a japanese case of human herpes virus-8-associated multicentric castleman disease complicated by hemophagocytic syndrome].we report a japanese case of human herpes virus-8 (hhv-8)-associated multicentric castleman disease(mcd) complicated by hemophagocytic syndrome(hps). a 60-year-old man presented with persistent fever and progressive pancytopenia in june 2004. on physical examination, anemia, icterus, hepatosplenomegaly, and generalized lymphadenopathy were detected. laboratory findings showed elevated levels of serum ferritin and soluble interleukin-2 receptor. anti-human immunodeficiency virus (hiv) antibody wa ...200818701866
'pyogenic granuloma-like kaposi's sarcoma' on the hands: immunohistochemistry and human herpesvirus-8 detection. 200818761551
mortality among hiv-1- and human herpesvirus type 8-affected mother-infant pairs in zambia.to determine the respective trends in mortality of zambian mother-infant pairs based on maternal infection with hiv-1 and human herpesvirus type 8 (hhv-8).200818768489
bortezomib-induced enzyme-targeted radiation therapy in herpesvirus-associated tumors.we investigated the possibility of using a pharmacologic agent to modulate viral gene expression to target radiotherapy to tumor tissue. in a mouse xenograft model, we had previously shown targeting of [(125)i]2'-fluoro-2'-deoxy-beta-d-5-iodouracil-arabinofuranoside ([(125)i]fiau) to tumors engineered to express the epstein-barr virus thymidine kinase (ebv-tk). here we extend those results to targeting of a therapeutic radiopharmaceutical [(131)i]fiau to slow or stop tumor growth or to achieve t ...200818776891
molecular concepts of virus infections causing skin cancer in organ transplant recipients.globally approximately 15% of all malignant tumors are caused by viruses and even a higher percentage is observed in organ transplant recipients (otr). here, nonmelanoma skin cancer (nmsc) is the most frequent malignancy, which correlates with cutaneous human papilloma virus (hpv) infection. in the present review, we reflect on some recent general concepts how tumor viruses can either act as direct or indirect carcinogens in the multistep process of carcinogenesis. immunosuppressive drugs in otr ...200818785959
symptomatic pulmonary allograft kaposi's sarcoma in two lung transplant recipients.kaposi's sarcoma (ks) is associated with solid-organ transplantation, but is extremely rare after lung transplantation. in this report, we describe two unique cases of lung transplant recipients who developed ks in the lung allograft and were treated with sirolimus and liposomal doxorubicin. one patient survived 12 months after the diagnosis of ks; the other survived 3 months after diagnosis and was found to have concomitant ebv-negative, hhv-8-positive b-cell lymphoma. we demonstrate a partial ...200818786235
expression of egfr and follicular dendritic markers in lymphoid follicles from patients with castleman's disease.this study investigated the useful morphologic and immunophenotypic findings for the diagnosis of castleman's disease (cd). we focused on the distribution and expression of follicular dendritic cells (fdc) in lymphoid follicles from patients with cd. eleven cd cases of the hyaline vascular (hv) variant and six cases of the plasma cell (pc) variant were studied using tissue microarray and paraffin resistant monoclonal antibodies cd21, cd35, and egfr, a new novel marker of fdc, as well as an antib ...200818813826
the history of tumor virology.in the century since its inception, the field of tumor virology has provided groundbreaking insights into the causes of human cancer. peyton rous founded this scientific field in 1911 by discovering an avian virus that induced tumors in chickens; however, it took 40 years for the scientific community to comprehend the effect of this seminal finding. later identification of mammalian tumor viruses in the 1930s by richard shope and john bittner, and in the 1950s by ludwik gross, sparked the first ...200818829521
kaposi's sarcoma-associated herpesvirus forms a multimolecular complex of integrins (alphavbeta5, alphavbeta3, and alpha3beta1) and cd98-xct during infection of human dermal microvascular endothelial cells, and cd98-xct is essential for the postentry stage of infection.kaposi's sarcoma-associated herpesvirus (kshv) interacts with cell surface heparan sulfate (hs) and alpha3beta1 integrin during the early stages of infection of human dermal microvascular endothelial cells (hmvec-d) and human foreskin fibroblasts (hff), and these interactions are followed by virus entry overlapping with the induction of preexisting host cell signal pathways. kshv also utilizes the amino acid transporter protein xct for infection of adherent cells, and the xct molecule is part of ...200818829766
pulmonary arterial hypertension and hiv infection. 200818832888
kaposi's sarcoma-associated herpesvirus gh/gl: glycoprotein export and interaction with cellular receptors.the attachment, entry, and fusion of kaposi's sarcoma-associated herpesvirus (kshv) with target cells are mediated by complex machinery containing, among others, viral glycoprotein h (gh) and its alleged chaperone, gl. we observed that kshv gh, in contrast to its homologues in several other herpesviruses, is transported to the cytoplasm membrane independently from gl, but not vice versa. mutational analysis revealed that the n terminus of gh is sufficient for gl interaction. however, the entire ...200918945775
the pathobiology of kaposi's sarcoma: advances since the onset of the aids epidemic.since the perplexing early kaposi's sarcoma (ks) observations at the dawn of the acquired immunodeficiency syndrome epidemic, ks has been extensively studied, revealing a complex disease. the identification and complete elucidation of the genome of its causal agent, the ks-associated herpesvirus/human herpesvirus 8, have shed important insights into the pathobiology of this disease. the purpose of this review is to describe the scientific advances and understanding of ks over the past three deca ...200818976418
viral inhibitor of apoptosis vflip/k13 protects endothelial cells against superoxide-induced cell death.human herpesvirus 8 (hhv-8) is the etiological agent of kaposi's sarcoma (ks). hhv-8 encodes an antiapoptotic viral fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein (vflip/k13). the antiapoptotic activity of vflip/k13 has been attributed to an inhibition of caspase 8 activation and more recently to its capability to induce the expression of antiapoptotic proteins via activation of nf-kappab. our study provides the first proteome-wide analysis of the effect ...200918987137
intracellular signaling mechanisms and activities of human herpesvirus 8 interleukin-6.human herpesvirus 8 (hhv-8)-encoded viral interleukin-6 (vil-6) has been implicated as a key factor in virus-associated neoplasia because of its proproliferative and survival effects and also in view of its angiogenic properties. a major difference between vil-6 and human il-6 (hil-6) is that vil-6, uniquely, is largely retained and can signal intracellularly. while vil-6 is generally considered to be a lytic gene, several reports have noted its low-level expression in latently infected primary ...200918987143
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
shhh! silencing by microrna-155.small rnas mediate a diverse pot-pourri of post-transcriptional silencing mechanisms, ranging from 'classical' rna interference (rnai), to gene repression by micrornas (mirnas), to maintenance of genomic stability by repeat-associated small rnas. here, we review recent findings on the function of mir-155, particularly its roles in mammalian innate and adaptive immunity, viral infection and oncogenesis.200919008191
the trafficking and regulation of membrane receptors by the ring-ch ubiquitin e3 ligases.ubiquitylation of membrane receptors is recognised as a critical post-translational modification, governing their regulation and function. following ubiquitylation, membrane proteins may be internalised, recycled or degraded via lysosomal or proteasomal pathways. viruses have appropriated these cellular pathways as a mechanism of immune evasion. ring (really interesting new gene)-ch ubiquitin e3 ligases were initially identified from the kaposi's associated herpesvirus (kshv) and their founding ...200919013150
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
expression of vflip in a lentiviral vaccine vector activates nf-{kappa}b, matures dendritic cells, and increases cd8+ t-cell responses.lentiviral vectors deliver antigens to dendritic cells (dcs) in vivo, but they do not trigger dc maturation. we therefore expressed a viral protein that constitutively activates nf-kappab, vflip from kaposi's sarcoma-associated herpesvirus (kshv), in a lentivector to mature dcs. vflip activated nf-kappab in mouse bone marrow-derived dcs in vitro and matured these dcs to a similar extent as lipopolysaccharide; costimulatory markers cd80, cd86, cd40, and icam-1 were upregulated and tumor necrosis ...200919036811
gene regulation and functional alterations induced by kaposi's sarcoma-associated herpesvirus-encoded orfk13/vflip in endothelial cells.kaposi's sarcoma (ks) is an angioproliferative inflammatory disorder induced by endothelial cell infection with the ks-associated herpesvirus (kshv). orfk13/vflip, one of the kshv genes expressed in ks, encodes a 188-amino-acid protein which binds to the ikappab kinase (ikk) complex to activate nf-kappab. we examined orfk13/vflip contribution to ks phenotype and potential for therapeutic targeting. retroviral transduction of orfk13/vflip into primary human endothelial cells induces the spindle m ...200919091861
tandem array-based expression screens identify host mrna targets of virus-encoded micrornas.micrornas (mirnas) are short noncoding rnas of cellular and viral origin that post-transcriptionally regulate gene expression through imperfect base pairing to their mrna targets. because the recognition sequences of mirnas for their targets are short and may be discontinuous, bioinformatic prediction of targets is difficult. here we present an approach to the experimental identification of the mrna targets of mirnas encoded by the kaposi's sarcoma-associated herpesvirus (kshv). kshv encodes 17 ...200919098914
linking the kaposi's sarcoma-associated herpesvirus (kshv/hhv-8) to human malignancies.in 1994, the kaposi's sarcoma-associated herpesvirus (kshv/hhv-8) was identified as the etiologic agent of kaposi's sarcoma (ks). kshv has since been associated with two additional malignancies: primary effusion lymphoma and multicentric castleman's disease. in this chapter, we describe the current understanding of the pathogenesis, transmission, and prevalence of kshv, and its association mainly with ks. we describe evidence demonstrating that kshv is a causative agent for ks, and we present ot ...200919109790
in vitro and in vivo human herpesvirus 8 infection of placenta.herpesvirus infection of placenta may be harmful in pregnancy leading to disorders in fetal growth, premature delivery, miscarriage, or major congenital abnormalities. although a correlation between human herpesvirus 8 (hhv-8) infection and abortion or low birth weight in children has been suggested, and rare cases of in utero or perinatal hhv-8 transmission have been documented, no direct evidence of hhv-8 infection of placenta has yet been reported. the aim of this study was to evaluate the in ...200819115001
the epstein-barr virus g-protein-coupled receptor contributes to immune evasion by targeting mhc class i molecules for degradation.epstein-barr virus (ebv) is a human herpesvirus that persists as a largely subclinical infection in the vast majority of adults worldwide. recent evidence indicates that an important component of the persistence strategy involves active interference with the mhc class i antigen processing pathway during the lytic replication cycle. we have now identified a novel role for the lytic cycle gene, bilf1, which encodes a glycoprotein with the properties of a constitutive signaling g-protein-coupled re ...200919119421
successful treatment with liposomal doxorubicin for widespread kaposi's sarcoma and human herpesvirus-8 related severe hemophagocytic syndrome in a patient with acquired immunodeficiency syndrome.hemophagocytic syndrome (hps) sometimes occurres in patients with acquired immunodeficiency syndrome (aids). human herpesvirus-8 (hhv-8)/kaposi's sarcoma (ks)-associated herpesvirus has so far been recognized as a trigger of hps in immunosuppressed subject. we describe a 39-year-old man with aids who had widespread mucocutaneous and pulmonary ks and severe hps. no opportunistic infections or neoplasias were detected except for ks. hhv-8-dna could be detected in this patient by polymerase chain r ...200919130173
impact of hiv infection and kaposi sarcoma on human herpesvirus-8 mucosal replication and dissemination in uganda.kaposi sarcoma (ks) is the leading cause of cancer in uganda and occurs in people with and without hiv. human herpesvirus-8 (hhv-8) replication is important both in transmission of hhv-8 and progression to ks. we characterized the sites and frequency of hhv-8 detection in ugandans with and without hiv and ks.200919156206
clinical course of classic kaposi's sarcoma in hiv-negative patients treated with the hiv protease inhibitor indinavir.hiv protease inhibitors have been shown to exert antiangiogenic and antitumor actions independently from their antiretroviral effect. based on these studies, hiv-seronegative patients with classic kaposi's sarcoma were treated with indinavir and followed for clinical evolution, drug pharmacokinetics and kaposi's sarcoma biomarkers. a favorable clinical course was associated with high drug plasma levels, reduced production of basic fibroblast growth factor, lower numbers of circulating endothelia ...200919169139
the role of immune suppression and hhv-8 in the increasing incidence of hiv-associated multicentric castleman's disease.in hiv cohorts with access to highly active antiretroviral therapy (haart), the incidence of kaposi's sarcoma (ks) is falling; however, the incidence of multicentric castleman's disease (mcd) in hiv has not previously been described.200919179554
[oropharyngeal kaposi's sarcoma: about a case not associated to the human immunodeficiency virus]. 200819216469
identification and characterization of a new kaposi's sarcoma-associated herpesvirus replication and transcription activator (rta)-responsive element involved in rta-mediated transactivation.kaposi's sarcoma-associated herpesvirus (kshv) replication and transcription activator (rta) is well established as a key transcriptional activator that regulates the kshv life cycle from latency to lytic replication. it is expressed immediately after infection and activates a number of viral genes leading to virus replication. the rta-responsive element (rre) in the rta target gene promoters is critical for rta to mediate this transactivation. a number of non-conserved rres have been identified ...200919223488
genome-wide identification of binding sites for kaposi's sarcoma-associated herpesvirus lytic switch protein, rta.kaposi's sarcoma-associated herpesvirus (kshv) replication and transcription activator (rta) encoded by orf50 is a lytic switch protein for viral reactivation from latency. the expression of rta activates the expression of downstream viral genes, and is necessary for triggering the full viral lytic program. using chromatin immunoprecipitation assay coupled with a kshv whole-genome tiling microarray (chip-on-chip) approach, we identified a set of 19 rta binding sites in the kshv genome in a kshv- ...200919233445
anti-cancer agents. more about ks. 200819248279
nf-kappab p50 plays distinct roles in the establishment and control of murine gammaherpesvirus 68 latency.nf-kappab signaling is critical to the survival and transformation of cells infected by the human gammaherpesviruses epstein-barr virus and kaposi's sarcoma-associated herpesvirus. here we have examined how elimination of the nf-kappab transcription factor p50 from mice affects the life cycle of murine gammaherpesvirus 68 (mhv68). notably, mice lacking p50 in every cell type were unable to establish a sufficiently robust immune response to control mhv68 infection, leading to high levels of laten ...200919264770
mechanism of fas signaling regulation by human herpesvirus 8 k1 oncoprotein.herpesvirus 8 (hhv-8) oncoprotein k1 is linked to lymphoproliferation and suppression of apoptosis mediated by the fas death receptor. expression of k1 in transgenic mice induces accumulation of lymphoid tissue cells and lymphoma.200919276446
a kaposi's sarcoma-associated herpesvirus protein that forms inhibitory complexes with type i interferon receptor subunits, jak and stat proteins, and blocks interferon-mediated signal transduction.type i interferons (ifns) are important mediators of innate antiviral defense and function by activating a signaling pathway through their cognate type i receptor (ifnar). here we report that lytic replication of kaposi's sarcoma-associated herpesvirus (kshv) efficiently blocks type i ifn signaling and that an important effector of this blockade is the viral protein rif, the product of open reading frame 10. rif blocks ifn signaling by formation of inhibitory complexes that contain ifnar subunit ...200919279093
epstein-barr virus-induced expression of a novel human vault rna.non-protein-coding rnas (ncrnas) have recently emerged on the scene of genomic research as prominent players in the regulation of gene expression. many functionally characterized ncrnas have been shown to be differentially expressed in various organisms during specific environmental or developmental conditions, thus establishing regulatory networks crucial for shaping cellular life. here, we show that the expression of vault rnas (vtrnas) is specifically up-regulated in human lymphocytes upon in ...200919298825
activation of host translational control pathways by a viral developmental switch.in response to numerous signals, latent herpesvirus genomes abruptly switch their developmental program, aborting stable host-cell colonization in favor of productive viral replication that ultimately destroys the cell. to achieve a rapid gene expression transition, newly minted capped, polyadenylated viral mrnas must engage and reprogram the cellular translational apparatus. while transcriptional responses of viral genomes undergoing lytic reactivation have been amply documented, roles for cell ...200919300492
expression and molecular analysis of c-kit and pdgfrs in kaposi's sarcoma of different stages and epidemiological settings. 200919302534
mechanism of sustained activation of ribosomal s6 kinase (rsk) and erk by kaposi sarcoma-associated herpesvirus orf45: multiprotein complexes retain active phosphorylated erk and rsk and protect them from dephosphorylation.as obligate intracellular parasites, viruses exploit diverse cellular signaling machineries, including the mitogen-activated protein-kinase pathway, during their infections. we have demonstrated previously that the open reading frame 45 (orf45) of kaposi sarcoma-associated herpesvirus interacts with p90 ribosomal s6 kinases (rsks) and strongly stimulates their kinase activities ( kuang, e., tang, q., maul, g. g., and zhu, f. (2008) j. virol. 82, 1838-1850 ). here, we define the mechanism by whic ...200919304659
geographic variation in the prevalence of kaposi sarcoma-associated herpesvirus and risk factors for transmission.the aim of the present study was to estimate the prevalence of kaposi sarcoma-associated herpesvirus (kshv) in the female general population, to define geographic variation in and heterosexual transmission of the virus.200919351262
all for one and one for all: herpesviral micrornas close in on their prey.herpesviruses subvert immune cell activation by inhibiting nk cell receptor (nkg2d)-activating ligands such as micb. a human cytomegalovirus microrna was recently shown to repress micb expression. nachmani et al. (2009) extend this finding to two other human herpesviruses, providing evidence for a conserved functional role of viral micrornas despite no sequence conservation among them.200919380110
diverse herpesvirus micrornas target the stress-induced immune ligand micb to escape recognition by natural killer cells.herpesviruses are known for their persistent lifelong latent infection, which is made possible by their vast repertoire of immune-evasion strategies. we have previously shown that a human cytomegalovirus (hcmv) microrna represses expression of the stress-induced natural killer (nk) cell ligand, micb, to escape recognition and consequent elimination by nk cells. here, we show functional conservation among diverse micrornas derived from different herpesviruses, including hcmv, kaposi's sarcoma-ass ...200919380116
human herpesvirus replication and abnormal cd8+ t cell activation and low cd4+ t cell counts in antiretroviral-suppressed hiv-infected patients.most hiv-infected patients receiving virologically suppressive antiretroviral therapy continue to have abnormal, generalized t cell activation. we explored whether the degree of ongoing cytomegalovirus (cmv), epstein-barr virus (ebv) and kaposi's sarcoma herpesvirus (kshv) replication was associated with higher virus-specific t cell activation and the failure to achieve normal absolute cd4+ t cell counts in the face of long-term suppressive antiretroviral therapy.200919381272
[picture in clinical hematology no. 36: case of primary effusion lymphoma with severe pericardial effusion]. 200919404013
kaposi's sarcoma. 200919415211
identification and characterization of the promoter region of kaposi's sarcoma-associated herpesvirus orf11.open reading frame 11 (orf11) of kaposi's sarcoma-associated herpesvirus belongs to a herpesviral homologous protein family that is conserved among members of the gamma-herpesvirus subfamily. little is known about the function of orf11 and how this viral gene is regulated in kshv life cycle. in this study, we have characterized the major transcript of the orf11 gene, which is located adjacent and in the opposite orientation to a well-characterized viral il-6 gene. northern blot analysis revealed ...200919428749
epigenetic regulation of kaposi's sarcoma-associated herpesvirus replication.kaposi's sarcoma-associated herpesvirus (kshv) is the causative agent of kaposi's sarcoma and b-lymphocyte disorders, primary effusion lymphoma (pel) and multicentric castleman's disease (mcd). kshv usually exists in a latent form in which the viral genome is circularized into an extrachormosomal episome. however, induction of lytic replication by environmental stimuli or chemical agents is important for the spread of kshv. the switch between latency and lytic replication is regulated by epigene ...200919429478
chemokine receptor ccr7 contributes to a rapid and efficient clearance of lytic murine gamma-herpes virus 68 from the lung, whereas bronchus-associated lymphoid tissue harbors virus during latency.murine gamma-herpes virus 68 is a natural rodent pathogen closely related to the human gamma-herpes viruses kaposi's sarcoma-associated herpes virus and ebv. by intranasally infecting wild-type and ccr7-deficient mice, we investigated whether ccr7 is necessary for viral clearance from the lung and the establishment of latency. we found during the lytic phase of infection that inflammation in lungs of ccr7(-/-) mice was more severe and viral load significantly higher compared with wild-type litte ...200919454682
aberrant herpesvirus-induced polyadenylation correlates with cellular messenger rna destruction.regulation of messenger rna (mrna) stability plays critical roles in controlling gene expression, ensuring transcript fidelity, and allowing cells to respond to environmental cues. unregulated enhancement of mrna turnover could therefore dampen cellular responses to such signals. indeed, several herpesviruses instigate widespread destruction of cellular mrnas to block host gene expression and evade immune detection. kaposi's sarcoma-associated herpesvirus (kshv) promotes this phenotype via the a ...200919468299
a standardized framework for accurate, high-throughput genotyping of recombinant and non-recombinant viral sequences.human immunodeficiency virus type-1 (hiv-1), hepatitis b and c and other rapidly evolving viruses are characterized by extremely high levels of genetic diversity. to facilitate diagnosis and the development of prevention and treatment strategies that efficiently target the diversity of these viruses, and other pathogens such as human t-lymphotropic virus type-1 (htlv-1), human herpes virus type-8 (hhv8) and human papillomavirus (hpv), we developed a rapid high-throughput-genotyping system. the m ...200919483099
lana-1, bcl-2, mcl-1 and hif-1alpha protein expression in hiv-associated kaposi sarcoma.human herpesvirus 8 (hhv8) is necessary for kaposi sarcoma (ks) to develop, but whether the tissue viral load is a marker of ks progression is still unclear. little is known about the level of expression of apoptosis-regulating proteins and of hypoxia-inducible factors (hifs) in ks tumour cells relative to hhv8 expression. we therefore investigated the expression of the latency-associated nuclear antigen (lana-1) of hhv8, bcl-2, mcl-1, bax, bcl-xl, caspase 3 and hif-1alphain ks tissue specimens ...200919484260
targeted therapy for kaposi sarcoma.kaposi sarcoma (ks) occurs as a result of kaposi sarcoma-associated herpesvirus (kshv) infection, typically in the context of one of several immunodeficient states. in the us, patients with ks may either be co-infected with hiv or receiving immunosuppressant therapy following solid-organ transplantation. systemic treatment of ks has traditionally involved one of several chemotherapeutic agents administered either in combination or as single agents, which typically provide reasonable response rat ...200919489649
[antigenic activity of human herpes virus type 8 proteins coding orfk8.1 and orf65].a peptide scanning of the sequences of human herpes virus type 8 (hhv-8) proteins coding orfk8.1 and orf65 was made. the antigenic activity of peptides was evaluated by elisa. the fragment 101-213 aa of orfk8.1-encoded protein was shown to consist of two sites containing linear b-epitopes that had a weak antigenic activity: 121-145 and 177-209 aa. the protein coding orf65 comprised 2 sites at which linear b-cell epitopes 78-110 aa (a weak antigenic activity) and 142-170 aa (a strong antigenic ac ...200919537097
kruppel-associated box domain-associated protein-1 as a latency regulator for kaposi's sarcoma-associated herpesvirus and its modulation by the viral protein kinase.kaposi's sarcoma-associated herpesvirus (kshv) has been linked to the development of kaposi's sarcoma, a major aids-associated malignancy, and to hematologic malignancies, including primary effusion lymphoma and multicentric castleman's disease. like other herpesviruses, kshv is capable of both latent and lytic replication. understanding the molecular details associated with this transition from latency to lytic replication is key to controlling virus spread and can affect the development of int ...200919584288
host shutoff is a conserved phenotype of gammaherpesvirus infection and is orchestrated exclusively from the cytoplasm.lytic infection with the two human gammaherpesviruses, kaposi's sarcoma-associated herpesvirus (kshv) and epstein-barr virus (ebv), leads to significant depletion of the cellular transcriptome. this host shutoff phenotype is driven by the conserved herpesviral alkaline exonuclease, termed sox in kshv and bglf5 in ebv, which in gammaherpesviruses has evolved the genetically separable ability to target cellular mrna. we now show that host shutoff is also a prominent consequence of murine gammaherp ...200919587049
mutational analysis of tp53, pten, pik3ca and ctnnb1/beta-catenin genes in human herpesvirus 8-associated primary effusion lymphoma.human herpesvirus 8 (hhv-8)-associated primary effusion lymphoma is a rare non-hodgkin's lymphoma often associated with epstein-barr virus (ebv) infection. mutations in tp53, pten, pik3ca, ctnnb1/beta-catenin genes and deletion of cdkn2a-arf (p14(arf)-p16(nk4a i) ) locus were investigated in sixteen primary primary effusion lymphoma tumors and seven primary effusion lymphoma cell lines using pcr and sequencing. tp53 mutations were detected in one primary primary effusion lymphoma tumor (6.2%) an ...200919608668
activation of mtorc1 signaling pathway in aids-related lymphomas.using immunohistochemistry with antibodies against the phosphoserine residues in both s6rp and 4e binding protein 1, we identified the activation of the mammalian target of rapamycin (mtorc)1 pathway in 29 cases of aids-related lymphoma. these cases represented a diverse spectrum of histological types of non-hodgkin lymphoma (24 cases) and classic hodgkin lymphoma (five cases). mtorc1 was also activated in the hyperplastic but not involuted follicles of hiv-associated lymphadenopathy in eight ca ...200919608873
ledgf/p75 proteins with alternative chromatin tethers are functional hiv-1 cofactors.ledgf/p75 can tether over-expressed lentiviral integrase proteins to chromatin but how this underlies its integration cofactor role for these retroviruses is unclear. while a single integrase binding domain (ibd) binds integrase, a complex n-terminal domain ensemble (nde) interacts with unknown chromatin ligands. whether integration requires chromatin tethering per se, specific nde-chromatin ligand interactions or other emergent properties of ledgf/p75 has been elusive. here we replaced the nde ...200919609362
positive staining of tumor-stage kaposi sarcoma with lymphatic marker d2-40.kaposi sarcoma (ks) is a vascular tumor first described by moritz kaposi (kohn) in 1872 and recently linked to human herpesvirus 8. all forms of ks share the same pathologic features, including atypical spindle cells and slitlike vascular spaces. the exact origin of the neoplastic endothelial cells (vascular vs lymphatic) has recently been debated.200919615538
human herpesvirus-8 and kaposi sarcoma after kidney transplantation: mechanisms of tumor genesis.human herpesviruses (hhvs) are able to escape from complete clearance by the immune system. their ability to become latent is due to their delicate interferences with the immune system. this characteristic makes some of them known as important tumor viruses. based on the prevalence of the seropositivity for the hhv-8, the world can be divided into 4 regions, one of which is the middle east with a seroprevalence of 5% to 20%. the incidence of iatrogenic kaposi sarcoma, a cancer linked with hhv-8 ...200919617659
inhibition of a viral enzyme by a small-molecule dimer disruptor.we identified small-molecule dimer disruptors that inhibit an essential dimeric protease of human kaposi's sarcoma-associated herpesvirus (kshv) by screening an alpha-helical mimetic library. next, we synthesized a second generation of low-micromolar inhibitors with improved potency and solubility. complementary methods including size exclusion chromatography and 1h-13c hsqc titration using selectively labeled 13c-met samples revealed that monomeric protease is enriched in the presence of inhibi ...200919633659
koebnerizing kaposi's sarcoma mimics a laparotomic hypertrophic scar in a liver transplant recipient. 200919642134
complex n-linked glycans on asn-89 of kaposi sarcoma herpes virus-encoded interleukin-6 mediate optimal function by affecting cytokine protein conformation.kaposi sarcoma-associated herpesvirus-encoded interleukin-6 (vil-6) and its human cellular homologue (huil-6) share similar biological functions. our previous work showed that n-linked glycosylation was required for optimal function of vil6 but not huil-6 (1). here we describe heterogeneity in the composition of the glycans of the two n-linked sites of vil-6. the asn-89 site of vil-6, found to be required for optimal cytokine function, is composed of complex glycans. the asn-78 site is composed ...200919690161
complete remission in a patient with human herpes virus-8 negative multicentric castleman disease using chop chemotherapy.multicentric castleman disease (mcd) is a rare lymphoproliferative disorder. although mcd pathogenesis is unclear, studies have suggested that human herpesvirus 8 (hhv-8) may be associated with the disorder. recent reports have identified mcd cases without viral infection. a 43-year-old woman presented to our hospital for fever and myalgia of 6 months' duration. the complete blood count revealed an elevated leukocyte count (15.1x10(3)/microl) and a decreased hemoglobin level of 10.0 g/dl. the c- ...200919707509
viral interferon regulatory factors.upon viral infection, the major defensive strategy employed by the host immune system is the activation of the interferon (ifn)-mediated antiviral pathway, which is overseen by ifn regulatory factors (irfs). in order to complete their life cycles, viruses must find a way to modulate the host ifn-mediated immune response. kaposi's sarcoma-associated herpesvirus (kshv), a human tumor-inducing herpesvirus, has developed a unique mechanism for antagonizing cellular ifn-mediated antiviral activity by ...200919715458
cd20 expression in the hhv-8-infected lymphoid cells in multicentric castleman disease. 200919723153
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