scholarly journals Epidemiology and Treatment of Kaposi’s Sarcoma in HIV-1 Infected Individuals in a Poor Resource Setting

10.5772/25248 ◽  
2011 ◽  
Author(s):  
A. Ahmed ◽  
H.M. Muktar
Keyword(s):  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Resource Setting ◽  
Hiv 1

scholarly journals Interleukin-8 and Growth-Regulated Oncogene Alpha Mediate Angiogenesis in Kaposi's Sarcoma

2002 ◽  
Vol 76 (22) ◽  
pp. 11570-11583 ◽  
Author(s):  
Brian R. Lane ◽  
Jianguo Liu ◽  
Paul J. Bock ◽  
Dominique Schols ◽  
Michael J. Coffey ◽  
...  
Keyword(s):  
Cell Culture ◽  
Endothelial Cells ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Interleukin 8 ◽  
Cellular Growth ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Stimulation Of

ABSTRACT The development of the complex neoplasm Kaposi's sarcoma is dependent on infection with the Kaposi's sarcoma-associated herpesvirus (KSHV) and appears to be greatly enhanced by cytokines and human immunodeficiency virus type 1 (HIV-1) Tat. Interleukin-8 (IL-8) and growth-regulated oncogene alpha (GRO-α) are chemokines involved in chemoattraction, neovascularization, and stimulation of HIV-1 replication. We have previously demonstrated that production of GRO-α is stimulated by exposure of monocyte-derived macrophages (MDM) to HIV-1. Here we show that exposure of MDM to HIV-1, viral Tat, or viral gp120 leads to a substantial increase in IL-8 production. We also demonstrate that IL-8 and GRO-α are induced by KSHV infection of endothelial cells and are crucial to the angiogenic phenotype developed by KSHV-infected endothelial cells in cell culture and upon implantation into SCID mice. Thus, the three known etiological factors in Kaposi's sarcoma pathogenesis—KSHV, HIV-1 Tat, and cellular growth factors—might be linked, in part, through induction of IL-8 and GRO-α.

scholarly journals HIV-1 Tat Regulates Endothelial Cell Cycle Progression via Activation of the Ras/ERK MAPK Signaling Pathway

2006 ◽  
Vol 17 (4) ◽  
pp. 1985-1994 ◽  
Author(s):  
Elena Toschi ◽  
Ilaria Bacigalupo ◽  
Raffaele Strippoli ◽  
Chiara Chiozzini ◽  
Anna Cereseto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Kaposi's Sarcoma ◽  
Cell Cycle Progression ◽  
Kaposi’S Sarcoma ◽  
Mapk Signaling ◽  
Small Gtpases ◽  
Mitogen Activated Protein Kinase ◽  
Endothelial Cell Proliferation ◽  
Hiv 1

Tat, the transactivator of HIV-1 gene expression, is released by acutely HIV-1-infected T-cells and promotes adhesion, migration, and growth of inflammatory cytokine-activated endothelial and Kaposi's sarcoma cells. It has been previously demonstrated that these effects of Tat are due to its ability to bind through its arginine-glycine-aspartic (RGD) region to the α5β1 and αvβ3 integrins. However, the signaling pathways linking Tat to the regulation of cellular functions are incompletely understood. Here, we report that Tat ligation on human endothelial cells results in the activation of the small GTPases Ras and Rac and the mitogen-activated protein kinase ERK, specifically through its RGD region. In addition, we demonstrated that Tat activation of Ras, but not of Rac, induces ERK phosphorylation. We also found that the receptor proximal events accompanying Tat-induced Ras activation are mediated by tyrosine phosphorylation of Shc and recruitment of Grb2. Moreover, Tat enabled endothelial cells to progress through the G1 phase in response to bFGF, and the process is linked to ERK activation. Taken together, these data provide novel evidence about the ability of Tat to activate the Ras-ERK cascade which may be relevant for endothelial cell proliferation and for Kaposi's sarcoma progression.

scholarly journals A Case of Kaposi’s Sarcoma during Primary HIV-1 Infection

2011 ◽  
Vol 10 (6) ◽  
pp. 349-350
Author(s):  
Marlous L. Grijsen ◽  
Marion Cornelissen ◽  
Jan M. Prins
Keyword(s):  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Cd4 Counts ◽  
Hiv 1

The majority of cases of Kaposi’s sarcoma (KS) occur at low CD4 counts during chronic HIV-1 infection. We present a case of KS which was diagnosed during primary HIV-1 infection. This report aims to draw attention that KS may occur early in the course of HIV-1 infection and that primary HIV-1 infection may rapidly progress to AIDS.

scholarly journals HIV-1 Tat Interacts with a Kaposi’s Sarcoma-Associated Herpesvirus Reactivation-Upregulated Antiangiogenic Long Noncoding RNA, LINC00313, and Antagonizes Its Function

2019 ◽  
Vol 94 (3) ◽  
Author(s):  
Wan-Shan Yang ◽  
Ting-Yu Lin ◽  
Lung Chang ◽  
Wayne W. Yeh ◽  
Shih-Ching Huang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Endothelial Cell ◽  
Cell Motility ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Hiv Tat ◽  
Lytic Reactivation ◽  
Hiv 1

ABSTRACT Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma (KS), an AIDS-defining cancer with abnormal angiogenesis. The high incidence of KS in human immunodeficiency virus (HIV)-infected AIDS patients has been ascribed to an interaction between HIV type 1 (HIV-1) and KSHV, focusing on secretory proteins. The HIV-1 secreted protein HIV Tat has been found to synergize with KSHV lytic proteins to induce angiogenesis. However, the impact and underlying mechanisms of HIV Tat in KSHV-infected endothelial cells undergoing viral lytic reactivation remain unclear. Here, we identified LINC00313 as a novel KSHV reactivation-activated long noncoding RNA (lncRNA) that interacts with HIV Tat. We found that LINC00313 overexpression inhibits cell migration, invasion, and tube formation, and this suppressive effect was relieved by HIV Tat. In addition, LINC00313 bound to polycomb repressive complex 2 (PRC2) complex components, and this interaction was disrupted by HIV Tat, suggesting that LINC00313 may mediate transcription repression through recruitment of PRC2 and that HIV Tat alleviates repression through disruption of this association. This notion was further supported by bioinformatics analysis of transcriptome profiles in LINC00313 overexpression combined with HIV Tat treatment. Ingenuity Pathway Analysis (IPA) showed that LINC00313 overexpression negatively regulates cell movement and migration pathways, and enrichment of these pathways was absent in the presence of HIV Tat. Collectively, our results illustrate that an angiogenic repressive lncRNA, LINC00313, which is upregulated during KSHV reactivation, interacts with HIV Tat to promote endothelial cell motility. These results demonstrate that an lncRNA serves as a novel connector in HIV-KSHV interactions. IMPORTANCE KS is a prevalent tumor associated with infections with two distinct viruses, KSHV and HIV. Since KSHV and HIV infect distinct cell types, the virus-virus interaction associated with KS formation has focused on secretory factors. HIV Tat is a well-known RNA binding protein secreted by HIV. Here, we revealed LINC00313, an lncRNA upregulated during KSHV lytic reactivation, as a novel HIV Tat-interacting lncRNA that potentially mediates HIV-KSHV interactions. We found that LINC00313 can repress endothelial cell angiogenesis-related properties potentially by interacting with chromatin remodeling complex PRC2 and downregulation of cell migration-regulating genes. An interaction between HIV Tat and LINC00313 contributed to the dissociation of PRC2 from LINC00313 and the disinhibition of LINC00313-induced repression of cell motility. Given that lncRNAs are emerging as key players in tissue physiology and disease progression, including cancer, the mechanism identified in this study may help decipher the mechanisms underlying KS pathogenesis induced by HIV and KSHV coinfection.

Inhibition of Angiogenesis by Type I Interferons in Models of Kaposi'S Sarcoma

1999 ◽  
Vol 14 (4) ◽  
pp. 257-262 ◽  
Author(s):  
C. Marchisone ◽  
R. Benelli ◽  
A. Albini ◽  
L. Santi ◽  
D. M. Noonan
Keyword(s):  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Inhibitory Effect ◽  
Type I Interferons ◽  
Endothelial Cell Migration ◽  
Type I ◽  
Type I Ifns ◽  
Hiv 1

Kaposi's Sarcoma (KS) is a pathology which occurs with increased frequency and in a particularly aggressive form in AIDS patients. The HIV-1 Tat protein appears to be an important co-factor in the induction of the extensive neo-vascularization associated with AIDS-KS. Tat acts as a chemoattractant for endothelial cells in vitro, inducing both chemotactic and invasive responses. Several clinical trials have been performed testing the effectiveness of diverse biological agents in therapy of KS, among these the type I interferons. Type I IFNs have diverse biological functions besides their anti-viral activity, including anti-angiogenic properties. We have shown that IFNα and IFNβ are potent inhibitors of both primary and immortalized endothelial cell migration and morphogenesis in vitro as well as neo-angiogenesis induced by HIV-1 Tat in vivo. The inhibitory effect of IFN class I on HIV-Tat associated angiogenesis further supports its use as a therapy for epidemic Kaposi's sarcoma. The use of recombinant IFNs at the levels required to obtain a therapeutic effect are associated with side effects and toxicity, therefore we are now developing a gene therapy approach for constant and local delivery type I IFNs.

Kaposi's sarcoma herpesvirus and HIV-1 seroprevalences in prostitutes in Djibouti

2002 ◽  
Vol 68 (2) ◽  
pp. 164-167 ◽  
Author(s):  
Anne-Genevi�ve Marcelin ◽  
Marc Grandadam ◽  
Philippe Flandre ◽  
Elisabeth Nicand ◽  
Catherine Milliancourt ◽  
...  
Keyword(s):  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Hiv 1

scholarly journals Molecular Mechanism of BST2/Tetherin Downregulation by K5/MIR2 of Kaposi's Sarcoma-Associated Herpesvirus

2009 ◽  
Vol 83 (19) ◽  
pp. 9672-9681 ◽  
Author(s):  
Mandana Mansouri ◽  
Kasinath Viswanathan ◽  
Janet L. Douglas ◽  
Jennie Hines ◽  
Jean Gustin ◽  
...  
Keyword(s):  
Kaposi's Sarcoma ◽  
Defense Mechanism ◽  
Transmembrane Protein ◽  
Kaposi’S Sarcoma ◽  
Dependent Manner ◽  
Type Ii ◽  
Amino Terminal ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus ◽  
Hiv 1

ABSTRACT K3/MIR1 and K5/MIR2 of Kaposi's sarcoma-associated herpesvirus (KSHV) are viral members of the membrane-associated RING-CH (MARCH) ubiquitin ligase family and contribute to viral immune evasion by directing the conjugation of ubiquitin to immunostimulatory transmembrane proteins. In a quantitative proteomic screen for novel host cell proteins downregulated by viral immunomodulators, we previously observed that K5, as well as the human immunodeficiency virus type 1 (HIV-1) immunomodulator VPU, reduced steady-state levels of bone marrow stromal cell antigen 2 (BST2; also called CD317 or tetherin), suggesting that BST2 might be a novel substrate of K5 and VPU. Recent work revealed that in the absence of VPU, HIV-1 virions are tethered to the plasma membrane in BST2-expressing HeLa cells. By targeting BST2, K5 might thus similarly overcome an innate antiviral host defense mechanism. Here we establish that despite its type II transmembrane topology and carboxy-terminal glycosylphosphatidylinositol (GPI) anchor, BST2 represents a bona fide target of K5 that is downregulated during primary infection by and reactivation of KSHV. Upon exit of the protein from the endoplasmic reticulum, lysines in the short amino-terminal domain of BST2 are ubiquitinated by K5, resulting in rapid degradation of BST2. Ubiquitination of BST2 is required for degradation, since BST2 lacking cytosolic lysines was K5 resistant and ubiquitin depletion by proteasome inhibitors restored BST2 surface expression. Thus, BST2 represents the first type II transmembrane protein targeted by K5 and the first example of a protein that is both ubiquitinated and GPI linked. We further demonstrate that KSHV release is decreased in the absence of K5 in a BST2-dependent manner, suggesting that K5 contributes to the evasion of intracellular antiviral defense programs.

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