Classic Kaposi's sarcoma in southern Sardinia, Italy.
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ABSTRACT:
SUBMITTER: Atzori L
PROVIDER: S-EPMC2409913 | biostudies-other | 2004 Oct
REPOSITORIES: biostudies-other
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Project description:Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically related to Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). It typically displays two different phases in its life cycle, the default latency and occasional lytic replication. The epigenetic modifications are thought to determine the fate of KSHV infection. Previous studies elegantly depicted epigenetic landscape of latent viral genome in in vitro cell culture systems. However, the physiologically relevant scenario in clinical KS tissue samples is unclear. In the present study, we established a protocol of ChIP-Seq for clinical KS tissue samples and mapped out the epigenetic landscape of KSHV genome in classic KS tissues. We examined AcH3 and H3K27me3 histone modifications on KSHV genome, as well as the genome-wide binding sites of latency associated nuclear antigen (LANA). Our results demonstrated that the enriched AcH3 was mainly restricted at latent locus while H3K27me3 was widespread on KSHV genome in classic KS tissues. The epigenetic landscape at the region of vIRF3 gene confirmed its silenced state in KS tissues. Meanwhile, the abundant enrichment of LANA at the terminal repeat (TR) region was also validated in the classic KS tissues, however, different LANA binding sites were observed on the host genome. Furthermore, we verified the histone modifications by ChIP-qPCR and found the dominant repressive H3K27me3 at the promoter region of replication and transcription activator (RTA) in classic KS tissues. Intriguingly, we found that the TR region in classic KS tissues was lacking in AcH3 histone modifications. These data now established the epigenetic landscape of KSHV genome in classic KS tissues, which provides new insights for understanding KSHV epigenetics and pathogenesis.
| S-EPMC5291540 | biostudies-literature
Project description:BackgroundClassic Kaposi's Sarcoma (cKS) is a rare vascular tumor associated with Human Herpesvirus 8 (KSHV) infection, nevertheless not all KSHV-infected individuals have cKS.ObjectiveWe investigated whether particular KIR/HLA receptor/ligand genotypes would be preferentially present in KSHV-infected and uninfected individuals who have or have not developed cKS.MethodsKIR/HLA genotypes were analyzed by molecular genotyping in 50 KSHV-infected individuals who did or did not have cKS and in 33 age-and sex-matched KSHV seronegative individuals.ResultsThere was no association of individual KIR, HLA or receptor ligand combinations with KSHV infection. However, activating KIR and KIR/HLA genotypes were significantly more frequent in cKS cases, specifically KIR3DS1, KIR2DS1, and KIR2DS1 with its HLA-C2 ligand.ConclusionA nonspecific inflammatory response triggered by activation of NK cells upon KIR-HLA interaction could be associated with the pathogenesis of KS.
| S-EPMC3379936 | biostudies-literature
Project description:The link between human herpesvirus 8 (KSHV) and Kaposi's sarcoma (KS) has been proven, but many important aspects including risk factors, genetic predisposition to tumor development, transmission of KSHV, and the pathogenic potential of different genotypes remain to be elucidated. Possible associations between clinical parameters and antibody levels, viral load fluctuations, and viral genotype were analyzed by quantitative real-time PCR, an in-house developed IFA assay, and sequence analysis of ORF K1-VR1 in blood, serum and saliva of 38 subjects with classic KS (cKS). KSHV lytic antibodies were significantly increased in stage IV compared to stage I and II patients (p = 0.006 and p = 0.041, respectively). KSHV blood, serum, and saliva viral load was comparable in all stages. The highest viral loads were detected in saliva, and they decreased in stages III-IV compared to stages I-II patients. Higher concentrations of lytic antibodies and higher viral loads were observed in fast progressing cKS patients, in whom KSHV detection from blood was also more frequent. Type A KSHV strain was almost exclusively present in rapid progressors (12/17 cases), while C type was mainly present in slow progressing patients (6/7 cases). Finally, detection of type A KSHV strain associated with higher blood viral loads. KSHV lytic antibody levels and viral load can be used to monitor clinical evolution of cKS. Infection supported by KSHV A subtype is associated with more rapid progressive disease. Careful monitoring and aggressive therapeutic protocols should be considered in patients with KSHV A-supported infection.
| S-EPMC2596973 | biostudies-literature
Project description: Not available
| S-EPMC3320504 | biostudies-literature
Project description:Kaposi's sarcoma-associated herpesvirus (KSHV) causes both AIDS-related Kaposi's sarcoma (KS) and classic KS, but their clinical presentations are different, and respective mechanisms remain to be elucidated. The KSHV K1 gene is reportedly involved in tumorigenesis through the immunoreceptor tyrosine-based activation motif (ITAM). Since we found the sequence variations in the K1 gene of KSHV isolated from AIDS-related KS and classic KS, we hypothesized that the transformation activity of the K1 gene contributes to the different clinical presentations. To evaluate our hypothesis, we compared the transformation activities of the K1 gene between AIDS-related KS and classic KS. We also analyzed ITAM activities and the downstream AKT and NF-κB. We found that the transformation activity of AIDS-related K1 was greater than that of classic K1, and that AIDS-related K1 induced higher ITAM activity than classic K1, causing more potent Akt and NF-κB activities. K1 downregulation by siRNA in AIDS-related K1 expressing cells induced a loss of transformation properties and decreased both Akt and NF-κB activities, suggesting a correlation between the transformation activity of K1 and ITAM signaling. Our study indicates that the increased transformation activity of AIDS-related K1 is associated with its clinical aggressiveness, whereas the weak transformation activity of classic type K1 is associated with a mild clinical presentation and spontaneous regression. The mechanism of spontaneous regression of classic KS may provide new therapeutic strategy to cancer.
| S-EPMC6478685 | biostudies-literature
Project description:Kaposi's sarcoma (KS) is a common neoplasm in Eastern and central Africa reflecting the spread of human gammaherpesvirus-8 (HHV-8), now considered a necessary causal agent for the development of KS. The endemic KS subtype can follow an aggressive clinical course with ulcerative skin lesions with soft tissue invasion or even bone or visceral involvement. In the latter cases, a thorough imaging work-up and better follow-up schedules are warranted. As KS is a chronic disease, the therapeutic goal is to obtain sustainable remission in cutaneous and visceral lesions and a good quality of life. Watchful monitoring may be sufficient in localized cutaneous forms. Potential therapeutic modalities for symptomatic advanced KS include systemic chemotherapies, immunomodulators, immune checkpoint inhibitors, and antiangiogenic drugs.
| S-EPMC9913747 | biostudies-literature
Project description: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 as high viral load levels and antibody titers. Reactivation also plays a role in the pathogenesis of KSHV-associated malignancies. To test this hypothesis, we employed an in vitro KSHV reactivation assay that measured increases in KSHV viral load in KSHV infected primary effusion lymphoma (PEL) cells and screened aqueous natural product extracts from KS endemic regions. Of 4,842 extracts from 38 countries, 184 (5%) caused KSHV reactivation. Extracts that caused reactivation came from a wide variety of plant families, and extracts from Africa, where KSHV is highly prevalent, caused the greatest level of reactivation. Time course experiments were performed using 28 extracts that caused the highest levels of reactivation. The specificity of the effects on viral replication was examined using transcriptional profiling of all viral mRNAs. The array data indicated that the natural extracts caused an ordered cascade of lytic replication similar to that seen after induction with synthetic activators. These in vitro data provide support for the "oncoweed" hypothesis by demonstrating basic biological plausibility.
| S-EPMC2857915 | biostudies-literature
Project description:Kaposi's Sarcoma (KS) is a proliferation of aberrant vascular structures lined by spindle cells, and is caused by a gammaherpes virus (HHV8/KSHV). Its course is aggravated by co-infection with HIV-1, where the timing of infection with HIV-1 and HHV8 is important for the clinical outcome. METHODS: In order to better understand the pathogenesis of KS, we have analysed tissue from two AIDS-KS lesions, and from normal skin by serial analysis of gene expression (SAGE). Semi-quantitative RT-PCR was then used to validate the results. RESULTS: The expression profile of AIDS-related KS (AIDS-KS) reflects an active process in the skin. Transcripts of HHV8 were found to be very low, and HIV-1 mRNA was not detected by SAGE, although it could be found using RT-PCR. Comparing the expression profile of AIDS-KS tissue with publicly available SAGE libraries suggested that AIDS-KS mRNA levels are most similar to those in an artificially mixed library of endothelial cells and leukocytes, in line with the description of KS lesions as containing spindle cells with endothelial characteristics, and an inflammatory infiltrate. At least 64 transcripts were found to be significantly elevated, and 28 were statistically downregulated in AIDS-KS compared to normal skin. Five of the upregulated mRNAs, including Tie 1 and sialoadhesin/CD169, were confirmed by semi-quantitative PCR to be elevated in additional AIDS-KS biopsies. Antibodies to sialoadhesin/CD169, a known marker of activated macrophages, were shown to specifically label tumour macrophages. CONCLUSION: The expression profile of AIDS-KS showed 64 genes to be significantly upregulated, and 28 genes downregulated, compared with normal skin. One of the genes with increased expression was sialoadhesin (CD169). Antibodies to sialoadhesin/CD169 specifically labelled tumour-associated macrophages, suggesting that macrophages present in AIDS-KS lesions belong to a subset of human CD169+ macrophages. Keywords: other
2003-07-16 | GSE514 | GEO
Project description:Kaposi's sarcoma-associated herpesvirus (KSHV) is the causal agent of all forms of Kaposi's sarcoma (KS), including AIDS-KS, endemic KS, classic KS and iatrogenic KS. Based on Open reading frame (ORF) K1 sequence analysis, KSHV has been classified into seven major molecular subtypes (A, B, C, D, E, F and Z). The distribution of KSHV strains varies according to geography and ethnicity. Xinjiang is a unique region where the seroprevalence of KSHV is significantly higher than other parts of China. The genotyping of KSHV strains in this region has not been thoroughly studied. The present study aimed to evaluate the frequency of KSHV genotypes isolated from KS tissues in Classical KS and AIDS KS patients from Xinjiang, China. ORF-K1 of KSHV from tissue samples of 28 KS patients was amplified and sequenced. Two subtypes of KSHV were identified according to K1 genotyping. Twenty-three of them belonged to subtype A, while five of them were subtype C. More genotype A than genotype C strains were found in both Classical KS and AIDS KS. No significant difference was found in the prevalence of different genotype between Classical KS and AIDS KS.
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Project description:Kaposi's sarcoma-associated herpesvirus (KSHV) is a human pathogenic γ-herpesvirus strongly associated with the development of Kaposi's Sarcoma and B cell proliferative disorders, including primary effusion lymphoma (PEL). The identification and functional investigation of non-coding RNAs expressed by KSHV is a topic with rapidly emerging importance. KSHV miRNAs derived from 12 stem-loops located in the major latency locus have been the focus of particular attention. Recent studies describing the transcriptome-wide identification of mRNA targets of the KSHV miRNAs suggest that these miRNAs have evolved a highly complex network of interactions with the cellular and viral transcriptomes. Relatively few KSHV miRNA targets, however, have been characterized at a functional level. Here, our current understanding of KSHV miRNA expression, targets, and function will be reviewed.
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