Human Herpesvirus Type 8 DNA Sequences in Cell-Free Plasma and Mononuclear Cells of Kaposi's Sarcoma Patients

Harrington, William J.; Bagasra, Omar; Sosa, Carlos; Bobroski, Lisa; Baum, Marianna K.; Wen, Xue; Cabral, Lisa; Byrne, Gerald E.; Pomerantz, Roger J.; Wood, Charles

doi:10.1093/infdis/174.5.1101

Cited by 76 publications

(66 citation statements)

References 12 publications

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“…For these experiments we were specifically interested in the interaction of the herpesvirus and the cultured endothelial cells, and wished to avoid the confounding effects of other contaminating cells on gene expression. For the apoptosis experiments, we hoped to generate conditions more analogous to the in vivo scenario, in which B cells are thought to harbor virus which then infects surrounding endothelial cells (41,53,54). The co-culture experiments resulted in a less robust infection (z 10-20%), but this may more closely mirror the in vivo scenario.…”

Section: Discussionmentioning

confidence: 99%

Human Herpesvirus-8 Infection of Primary Pulmonary Microvascular Endothelial Cells

Bull¹,

Meadows²,

Coldren³

et al. 2008

Am J Respir Cell Mol Biol

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Human herpesvirus-8 (HHV-8) is the causative agent of Kaposi's sarcoma and is associated with the angioproliferative disorders primary effusion lymphoma and multicentric Castleman's disease. Evidence of HHV-8 infection within the pulmonary vasculature of patients with idiopathic pulmonary arterial hypertension (IPAH) has been described. We hypothesize that HHV-8 infection of pulmonary microvascular endothelial cells results in an apoptotic-resistant phenotype characteristic of severe pulmonary arterial hypertension. Our objective was to investigate the ability of HHV-8 to infect human pulmonary microvascular endothelial cells in vitro and characterize the phenotypic effect of this infection. Human pulmonary microvascular endothelial cells were exposed to HHV-8 using two methods (direct virus and co-culture technique). The presence of lytic and latent infection was confirmed. Changes in endothelial cell gene and protein expression and effects on cellular apoptosis were measured. HHV-8 can both lytically and latently infect primary human pulmonary microvascular endothelial cells in vitro. HHV-8 infection results in significant changes in gene expression, including alterations of pathways important to cellular apoptosis. HHV-8 infection also alters expression of genes integral to the bone morphogenic protein pathway, including down-regulation of bone morphogenic protein-4. Other genes previously implicated in the development of PAH are affected by HHV-8 infection, and cells infected with HHV-8 are resistant to apoptosis.

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Section: Discussionmentioning

confidence: 99%

Human Herpesvirus-8 Infection of Primary Pulmonary Microvascular Endothelial Cells

Bull¹,

Meadows²,

Coldren³

et al. 2008

Am J Respir Cell Mol Biol

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“…[2][3][4][5][6][7] Viral DNA is detected in peripheral-blood mononuclear cells (PBMCs) and in cell-free blood (ie, plasma or serum). 8,9 As with other gammaherpesviruses, lymphocytes harbor latent virus in vivo.…”

Section: Introductionmentioning

confidence: 99%

Effects of Chemotherapy in AIDS-Associated Non-Hodgkin's Lymphoma on Kaposi's Sarcoma Herpesvirus DNA in Blood

Lin

Lee

Kaplan

et al. 2009

JCO

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A B S T R A C T PurposeTo determine the relative frequency with which Kaposi's sarcoma-associated herpesvirus/HHV-8 (KSHV) DNA is detected in peripheral-blood mononuclear cells (PBMCs) and in plasma of patients with AIDS-KS and AIDS-associated non-Hodgkin's lymphoma (NHL; AIDS-NHL); to determine whether the presence of viral DNA in plasma reflects lysis of tumor cells or reflects the presence of viremia (ie, virion-encapsidated DNA); and to determine the effect of lymphoma therapy on KSHV DNA. Patients and MethodsSamples were obtained from patients enrolled in AIDS Malignancy Consortium clinical trials and from healthy donors. Real time PCR was used to quantify KSHV DNA in peripheral blood mononuclear cells (PBMC) and plasma. DNase digestion and fragment size determination studies were used to characterize the DNA detected.

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“…[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][11][12][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.…”

Section: Introductionmentioning

confidence: 99%

“…[6][7][8][9] Circulating B cells form the major virus reservoir in blood, [10][11][12][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.…”

Section: Introductionmentioning

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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Human Herpesvirus Type 8 DNA Sequences in Cell-Free Plasma and Mononuclear Cells of Kaposi's Sarcoma Patients

Cited by 76 publications

References 12 publications

Human Herpesvirus-8 Infection of Primary Pulmonary Microvascular Endothelial Cells

Human Herpesvirus-8 Infection of Primary Pulmonary Microvascular Endothelial Cells

Effects of Chemotherapy in AIDS-Associated Non-Hodgkin's Lymphoma on Kaposi's Sarcoma Herpesvirus DNA in Blood

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

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