Gene expression profile of AIDS-related Kaposi's sarcoma

Cornelissen, Marion; Kuyl, Antoinette C. van der; Burg, Remco van den; Zorgdrager, Fokla; Noesel, Carel J. M. van; Goudsmit, Jaap

doi:10.1186/1471-2407-3-7

Cited by 43 publications

(31 citation statements)

References 51 publications

(51 reference statements)

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“…Recently it was shown by serial analysis of gene expression (SAGE) that HO-1 expression in AIDS-KS biopsy tissue is significantly greater than in control tissue. 60 Here we independently confirm this finding with quantitative RT-PCR results on cutaneous AIDS-KS tissue that show elevated HO-1 mRNA compared with normal skin. Furthermore, immunohistochemistry on oral AIDS-KS lesional tissue revealed increased expression of HO-1 protein compared with normal tissue at the tumor margin.…”

supporting

confidence: 77%

Kaposi sarcoma-associated herpesvirus (KSHV) induces heme oxygenase-1 expression and activity in KSHV-infected endothelial cells

McAllister

Hansen

Ruhl

et al. 2004

Blood

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IntroductionKaposi sarcoma-associated herpesvirus (KSHV; also human herpesvirus-8) is implicated in all clinical forms of KS 1,2 as well as the lymphoproliferative disorders primary effusion lymphoma (PEL) 3,4 and multicentric Castleman disease (MCD). 5 Endothelial cells harbor the KSHV genome in vivo, 1,6,7 are permissive for virus infection in vitro, [8][9][10][11] and are thought to be the precursors of spindle cells. [12][13][14][15] We and others have shown that in vitro infection of human dermal microvascular endothelial cells (DMVECs) with KSHV induces a spindle cell morphology and characteristics of a transformed phenotype, including loss of contact inhibition and growth in soft agar. [8][9][10][11] Because explanted KS cells fail to maintain the KSHV genome following serial passage, 16,17 in vitro infection of DMVECs has proved to be an invaluable tool for the study of KSHV pathogenic mechanisms. 18,19 KSHV, like other herpesviruses, has a substantial coding capacity that includes viral genes unique to this human pathogen, genes that share homology with other members of the herpesviridae, as well as genes that appear to have originated in the host genome. 20,21 Of note, at least 3 of these gene products, vFLIP (viral Fas-associating protein with death domain-like interleukin-1␤ [IL-1␤]-converting enzyme [FLICE]-inhibitory protein), viral cyclin (vCYC), and latency-associated nuclear antigen (LANA), are believed to comprise the viral latency expression program and are consistently expressed in all virally infected cells in KS, PEL, and MCD. [22][23][24] The gene product of open reading frame 71 (ORF 71), vFLIP, is thought to play an important role in prevention of apoptotic cell death. 25 The activity of a homolog of cellular cyclin D, vCYC (ORF 72), 26 together with the modulation of cellular transcription wrought by LANA (ORF 73) 27 is thought to be involved in KSHV-induced host cell transformation. Additionally, LANA is indispensable for maintenance of the viral genome. 28 Other gene products, such as viral G-protein-coupled receptor (vGCR) 29,31 are classified as lytic gene products and are expressed in only a minority of cells in vivo. [32][33][34] Although reactivation of KSHV from the latent state and subsequent completion of the viral lytic expression cascade is incompatible with survival of a host cell, lytic gene products are thought to have paracrine influences on both latently infected and uninfected cells and are thus considered vital for lesion development. 35 We have used our previously described in vitro KS model to dissect viral mechanisms of pathogenesis. 18,19 The salient features of our model include recapitulation of KS cell physiology, including spindle cell formation, loss of contact inhibition, and anchoragedependent growth restriction; long-term propagation of predominantly latently infected cells; and the ability to generate ageand passage-matched KSHV-infected and uninfected cultures. 11 This system has been amenable to gene expression profiling by cDNA microarrays and has ...

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supporting

confidence: 77%

Kaposi sarcoma-associated herpesvirus (KSHV) induces heme oxygenase-1 expression and activity in KSHV-infected endothelial cells

McAllister

Hansen

Ruhl

et al. 2004

Blood

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“…Thus, the resulting infected LECs or BECs are more similar to one another than their uninfected counterparts. This is in agreement with the observation that KS spindle cells do not represent the typical transcriptional profile of LECs nor of BECs, but instead are poorly differentiated, expressing markers of both lymphatic and blood vessel endothelium (Cornelissen et al, 2003;Lagos et al, 2007;Pyakurel et al, 2006b; H.W. .…”

Section: Ks Histogenesis and The Biology Of The Ks Spindle Cellssupporting

confidence: 78%

KSHV Paracrine Effects on Tumorigenesis

Jochmann¹,

Lorenz²,

Chudasama³

et al. 2012

Herpesviridae - A Look Into This Unique Family of Viruses

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“…However, other investigators have reported inconsistent CD31 levels in nodular tumor tissue compared to those in blood vessels or compared to CD34 levels (67). The expression of VE-cadherin mRNA in KS tissue was found previously to be increased compared to that in normal skin (18). However, the same study reported increased message levels for MHC-I.…”

Section: Discussionmentioning

confidence: 62%

Remodeling of Endothelial Adherens Junctions by Kaposi's Sarcoma-Associated Herpesvirus

Mansouri¹,

Rose²,

Moses³

et al. 2008

J Virol

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Vascular endothelial cadherin (VE-cadherin) connects neighboring endothelial cells (ECs) via interendothelial junctions and regulates EC proliferation and adhesion during vasculogenesis and angiogenesis. The cytoplasmic domain of VE-cadherin recruits ␣-and ␤-catenins and ␥-catenin, which interact with the actin cytoskeleton, thus modulating cell morphology. Dysregulation of the adherens junction/cytoskeletal axis is a hallmark of invasive tumors. We now demonstrate that the transmembrane ubiquitin ligase K5/MIR-2 of Kaposi's sarcoma-associated herpesvirus targets VE-cadherin for ubiquitin-mediated destruction, thus disturbing EC adhesion. In contrast, N-cadherin levels in K5-expressing cells were increased compared to those in control cells. Steady-state levels of ␣-and ␤-catenins and ␥-catenin in K5-expressing ECs were drastically reduced due to proteasomal destruction. Moreover, the actin cytoskeleton was rearranged, resulting in the dysregulation of EC barrier function as measured by electric cell-substrate impedance sensing. Our data represent the first example of a viral protein targeting adherens junction proteins and suggest that K5 contributes to EC proliferation, vascular leakage, and the reprogramming of the EC proteome during Kaposi's sarcoma tumorigenesis.

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Gene expression profile of AIDS-related Kaposi's sarcoma

Cited by 43 publications

References 51 publications

Kaposi sarcoma-associated herpesvirus (KSHV) induces heme oxygenase-1 expression and activity in KSHV-infected endothelial cells

Kaposi sarcoma-associated herpesvirus (KSHV) induces heme oxygenase-1 expression and activity in KSHV-infected endothelial cells

KSHV Paracrine Effects on Tumorigenesis

Remodeling of Endothelial Adherens Junctions by Kaposi's Sarcoma-Associated Herpesvirus

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