The Natural History of Kaposi's Sarcoma in the Acquired Immunodeficiency Syndrome

Safai, Bijan; Johnson, Kevin R.; Myskowski, Patricia L.; Koziner, Benjamín; Yang, Soo Young; Cunningham‐Rundles, Susanna; Godbold, James; Dupont, Bo

doi:10.7326/0003-4819-103-5-744

Cited by 231 publications

(85 citation statements)

References 12 publications

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“…This is further sustained by the observation that these genes are strongly transcribed, although KSHV encodes a DNA exonuclease SOX/orf37, which mediates the shut-off of host transcription during the lytic cycle of KSHV (Chandriani & Ganem, 2007). All these secreted proteins appear to cooperate in the activation of endothelial cells and are important for tumour neovascularisation and KS development Ensoli et al, 1989;Ganem, 1995;Safai et al, 1985).…”

Section: Interplay Between Inflammatory Cytokines and Angiogenic Factmentioning

confidence: 92%

KSHV Paracrine Effects on Tumorigenesis

Jochmann¹,

Lorenz²,

Chudasama³

et al. 2012

Herpesviridae - A Look Into This Unique Family of Viruses

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Section: Interplay Between Inflammatory Cytokines and Angiogenic Factmentioning

confidence: 92%

KSHV Paracrine Effects on Tumorigenesis

Jochmann¹,

Lorenz²,

Chudasama³

et al. 2012

Herpesviridae - A Look Into This Unique Family of Viruses

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“…47 In this situation, calcineurin-NFAT signaling may promote the reactivation of latent KSHV residing in B cells and contribute to KS development. 48,49 Future studies will be directed toward the relation between the extent of lymphocyte activation and KSHV viremia.…”

Section: Discussionmentioning

confidence: 99%

Targeted inhibition of calcineurin signaling blocks calcium-dependent reactivation of Kaposi sarcoma–associated herpesvirus

Zoeteweij

Moses

Rinderknecht

et al. 2001

Blood

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Kaposi sarcoma-associated herpesvirus (KSHV) is associated with KS, primary effusion lymphoma (PEL), and multicentric Castleman disease. Reactivation of KSHV in latently infected cells and subsequent plasma viremia occur before the development of KS. Intracellular signaling pathways involved in KSHV reactivation were studied. In latently infected PEL cells (BCBL-1), KSHV reactivation in single cells was determined by quantitative flow cytometry. Viral particle production was determined by electron microscope analyses and detection of minor capsid protein in culture supernatants.Agents that mobilized intracellular calcium (ionomycin, thapsigargin) induced expression of KSHV lytic cycle-associated proteins and led to increased virus production. Calcium-mediated virus reactivation was blocked by specific inhibitors of calcineurin-dependent signal transduction (cyclosporine, FK506 IntroductionInfection with the ␥-herpesvirus Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is causally involved in KS, primary effusion lymphoma (PEL), and some forms of multicentric Castleman disease. [1][2][3][4][5] The detection of KSHV in peripheral blood leukocytes is strongly predictive of the future development of KS. [6][7][8][9] Circulating B cells form the major virus reservoir in blood, 10-13 though KSHV has been found in monocytes, CD8 ϩ T cells, and CD34 ϩ cells. 11,[14][15][16] Active replication in blood and subsequent plasma viremia likely disseminate the virus throughout the body, leading to infection of dermal lymphatic endothelial cells, which are believed to be precursor cells for KS. 5 Furthermore, in KS lesions, tumor spindle cells are latently infected by KSHV; a small subpopulation of lytically infected cells produces virus and lytic viral gene products, which may contribute to the maintenance or progression of KS lesions. In general, understanding the pathways that activate virus replication (latent-tolytic switch), in blood as well as in KS lesions, is an important issue in fully understanding KS pathogenesis.In experimental systems to date, KSHV infection of primary B cells in vitro has been inefficient and unstable. 13,17 However, latently infected B cell lines, derived from patients with PEL, and infected immortalized endothelial cells are useful tools to study KSHV reactivation. [18][19][20][21][22][23] Expression of the KSHV lytic cycleassociated immediate-early ORF 50 protein (Rta) is sufficient to induce the entire lytic cycle of active viral replication. 24 Ionomycin, a Ca ϩϩ -ionophore, is known to induce expression of the ORF 50 protein. 25,26 This suggests that calcium-dependent signaling pathways may play a role in virus reactivation.In the immune system, calcium signaling is essential for the expression of many inducible genes encoding cytokines and cell surface receptors. 27,28 One of the enzymes activated by a sustained rise in [Ca ϩϩ ] i is calcineurin, a ubiquitously expressed serinethreonine phosphatase. Activation of the Ca ϩϩ -calcineurin signaling cas...

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“…Kaposi's sarcoma (KS) with initial lung involvement is reported most often in immunocompromised patients, running a short fatal course, and the effects of treatment are not well described ( 1,2). We now report an immunocompetent patient with KS limited to the lung, who responded to vinblastine and thoracic irradiation but after 10 months developed a fatal treatment-related pneumonitis.…”

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confidence: 94%