Visualization of human herpesvirus type 8 in Kaposiʼs sarcoma by light and transmission electron microscopy

Orenstein, Jan M.; Alkan, Serhan; Blauvelt, Andrew; Jeang, Kuan‐Teh; Weinstein, Mark D.; Ganem, Don; Herndier, Brian

doi:10.1097/00002030-199705000-00001

Cited by 199 publications

(97 citation statements)

References 35 publications

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“…Although only a small subset (8 ± 10%) of cells within the lesions expressed ORF74, the receptor was found on NKand T-cells that in®ltrated the angioproliferative lesions. The low expression pro®le of ORF74 is in accordance with the expression pattern observed for other lytic HHV8 encoded genes in Kaposi's sarcoma lesions in humans (Staskus et al, 1997;Orenstein et al, 1997;Kirshner et al, 1999;Sun et al, 1999). In contrast, latently expressed HHV8 genes can be detected in almost all Kaposi's sarcoma tumour cells (Dupin et al, 1999), emphasizing the putative role of HHV8 in the pathogenesis of this disease.…”

Section: Orf74 From Hhv8supporting

confidence: 76%

Virally encoded 7TM receptors

Rosenkilde¹,

Waldhoer²,

Lüttichau

et al. 2001

Oncogene

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Section: Orf74 From Hhv8supporting

confidence: 76%

Virally encoded 7TM receptors

Rosenkilde¹,

Waldhoer²,

Lüttichau

et al. 2001

Oncogene

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“…Importantly, these features were retained in whole KS biopsies. Morphological studies have shown that most of the cells in KS lesions are latently infected, whereas a low fraction of cells from unknown origin appear to contain replicative virus (Orenstein et al, 1997;Grundhoff and Ganem, 2004). Of note, vGPCR is also expressed in a small subset of cells in KS (5-10%) (Chiou et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Remodeling of VE-cadherin junctions by the human herpes virus 8 G-protein coupled receptor

et al. 2010

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Kaposi Sarcoma (KS) are opportunistic tumors, associated with human herpes virus 8 (HHV8) infection. KS development is highly favored by immune-depression and remains the second most frequent tumor in acquired immune deficiency syndrome patients. Although it has been shown that experimental expression of the HHV8 G-proteincoupled receptor (vGPCR) in the endothelial compartment is alone sufficient to recapitulate the formation and progression of KS-like lesions, its functional effects on endothelial homeostasis are not fully understood. Here we show that vGPCR expression in endothelial cells induces an increase in paracellular permeability both in vivo and in vitro. By using pharmacological inhibitors and small interference RNA-based knockdown, we demonstrate an essential role for the PI(3)Kinase-c/Rac nexus in vGPCRmediated permeability. This was further accompanied by dramatic remodeling of VE-cadherin-dependent cell-cell junctions. Importantly, this in vitro vGPCR-initiated signaling signature was observed in a large panel of human KS. Altogether, our results support the hypothesis that endothelial vGPCR signaling is co-opted in KS, and unveil new key cellular targets for therapeutic intervention.

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“…For example, vFLIP blocks cytotoxic T-cell killing of HHV-8-infected cells by inhibiting Fas activation [43]; vMIP-II may restrict recruitment of Th1 lymphocytes to HHV-8-infected cells [44]; K1 may prevent class 2 MHC-mediated T cell activation by HHV-8 [45]; and K3 and K5 block cell surface display of class 1 MHC molecules on the cell surface [46]. Although the majority of cells within KS lesions show latent infection, a small subset expresses lytic cycle genes [47] and produce viral progeny [48].…”

Section: The Role Of Hhv-8mentioning

confidence: 99%

AIDS-associated Kaposi's sarcoma: Is there still a role for interferon alfa?

Krown

2007

Cytokine & Growth Factor Reviews

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Interferon alfa (IFNA) was one of the first agents to be used therapeutically in AIDS-associated Kaposi's sarcoma (KS) more than 25 years ago, and induces tumor regression in a subset of patients. Although much has been learned about the clinical role of IFNα in KS treatment, little is currently known about the mechanism(s) by which IFNA causes KS regression. This is despite a growing understanding of both KS pathogenesis and relevant IFNA activities. To a large extent other agents have supplanted IFNA as treatments for KS, but there may still remain a therapeutic role for IFNA, possibly in combination with other agents targeting angiogenesis and/or HHV-8-encoded human gene homologs that encode proteins involved in cell cycle regulation and signaling. KeywordsInterferon; Kaposi's sarcoma In 1995, when I was honored as a recipient of the ISICR Milstein Award, the AIDS epidemic had recently begun its 15 th year and the human immunodeficiency virus (HIV-1) had been isolated some 12 years previously [1]. However, the virus associated with Kaposi's sarcoma (KS), the most common AIDS-associated malignancy, had been described less than a year earlier [2], its significance was still in some question and its role in KS development had not been characterized, and the active combination drug regimens with which we now treat HIV infection had not yet become widely available. Recombinant interferon alfa preparations (IFNα2a and IFNα2b), which had received approval from the U.S. Food and Drug Administration (FDA) for treatment of AIDS-associated KS in 1988, were still the only approved drugs for systemic treatment of KS (the chemotherapeutic agent, liposomal doxorubicin, would receive FDA approval later in 1995, as did liposomal daunorubicin in 1996 and paclitaxel in 1997). Now, more than a quarter century after the first published reports describing AIDS and its association with KS [3-6] and our first modestly successful attempts to treat KS with IFNα [7], this agent is used infrequently to treat KS, although it still finds use in HIV-infected individuals co-infected with hepatitis C. In this brief review, I will summarize some of the history of IFNα in the treatment of AIDS-associated KS, concentrating on examples of clinical trials in which I have personally been involved, and consider whether there remains a potentially valuable role for this agent in KS treatment.

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Visualization of human herpesvirus type 8 in Kaposiʼs sarcoma by light and transmission electron microscopy

Cited by 199 publications

References 35 publications

Virally encoded 7TM receptors

Virally encoded 7TM receptors

Remodeling of VE-cadherin junctions by the human herpes virus 8 G-protein coupled receptor

AIDS-associated Kaposi's sarcoma: Is there still a role for interferon alfa?

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