KSHV

Giffin, Louise; Damania, Blossom

doi:10.1016/b978-0-12-800098-4.00002-7

Cited by 116 publications

(64 citation statements)

References 321 publications

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“…Like HPV and SV40, KSHV exploits the DDR to promote productive replication. While direct activation of cell division by latency proteins provides a potential link to oncogenesis [93], emerging evidence points to lytic reactivation as being critical in the initial events of cancer progression or establishment of a proper tumour microenvironment [102,103]. DDR activation impairs establishment of latency, thus KSHV blocks detrimental downstream effects.…”

Section: (B) Summarymentioning

confidence: 99%

Take your PIKK: tumour viruses and DNA damage response pathways

Pancholi

Price

Weitzman

2017

Phil. Trans. R. Soc. B

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Viruses regulate cellular processes to facilitate viral replication. Manipulation of nuclear proteins and pathways by nuclear replicating viruses often causes cellular genome instability that contributes to transformation. The cellular DNA damage response (DDR) safeguards the host to maintain genome integrity, but DNA tumour viruses can manipulate the DDR to promote viral propagation. In this review, we describe the interactions of DNA tumour viruses with the phosphatidylinositol 3-kinase-like protein kinase (PIKK) pathways, which are central regulatory arms of the DDR. We review how signalling through the ataxia telangiectasia mutated (ATM), ataxia telangiectasia and Rad3 related (ATR), and DNA-dependent protein kinases (DNA-PK) influences viral life cycles, and how their manipulation by viral proteins may contribute to tumour formation.This article is part of the themed issue 'Human oncogenic viruses'.

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Section: (B) Summarymentioning

confidence: 99%

Take your PIKK: tumour viruses and DNA damage response pathways

Pancholi

Price

Weitzman

2017

Phil. Trans. R. Soc. B

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“…2-D cultures lack many features of the native microenvironment in vivo . As a result, many in vivo physiologic properties that may be crucial to defining a cell’s growth and gene expression, such as signaling through certain pathways ( e.g., Notch), can be altered151617. When growing tumor cells in 2-D, such differences may hinder the reproduction of important in vivo features151819.…”

mentioning

confidence: 99%

3-D Microwell Array System for Culturing Virus Infected Tumor Cells

Assal

Gürkan

Chen

et al. 2016

Sci Rep

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Cancer cells have been increasingly grown in pharmaceutical research to understand tumorigenesis and develop new therapeutic drugs. Currently, cells are typically grown using two-dimensional (2-D) cell culture approaches, where the native tumor microenvironment is difficult to recapitulate. Thus, one of the main obstacles in oncology is the lack of proper infection models that recount main features present in tumors. In recent years, microtechnology-based platforms have been employed to generate three-dimensional (3-D) models that better mimic the native microenvironment in cell culture. Here, we present an innovative approach to culture Kaposi’s sarcoma-associated herpesvirus (KSHV) infected human B cells in 3-D using a microwell array system. The results demonstrate that the KSHV-infected B cells can be grown up to 15 days in a 3-D culture. Compared with 2-D, cells grown in 3-D had increased numbers of KSHV latency-associated nuclear antigen (LANA) dots, as detected by immunofluorescence microscopy, indicating a higher viral genome copy number. Cells in 3-D also demonstrated a higher rate of lytic reactivation. The 3-D microwell array system has the potential to improve 3-D cell oncology models and allow for better-controlled studies for drug discovery.

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“…One of the critical steps in KSHV pathogenesis is the establishment of viral latency following primary infection, which is characterized by the inhibition of lytic gene expression and lytic viral replication (Giffin and Damania, 2014). In this study, we investigated the role of CTCF and cohesin factors in the establishment of viral latency following de novo KSHV infection.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the lytic cycle of Kaposi's sarcoma-associated herpesvirus by cohesin factors following de novo infection

2017

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Establishment of Kaposi’s sarcoma-associated herpesvirus (KSHV) latency following infection is a multistep process, during which polycomb proteins are recruited onto the KSHV genome, which is crucial for the genome-wide repression of lytic genes during latency. Strikingly, only a subset of lytic genes are expressed transiently in the early phase of infection prior to the binding of polycomb proteins onto the KSHV genome, which raises the question what restricts lytic gene expression in the first hours of infection. Here, we demonstrate that both CTCF and cohesin chromatin organizing factors are rapidly recruited to the viral genome prior to the binding of polycombs during de novo infection, but only cohesin is required for the genome-wide inhibition of lytic genes. We propose that cohesin is required for the establishment of KSHV latency by initiating the repression of lytic genes following infection, which is an essential step in persistent infection of humans.

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KSHV

Cited by 116 publications

References 321 publications

Take your PIKK: tumour viruses and DNA damage response pathways

Take your PIKK: tumour viruses and DNA damage response pathways

3-D Microwell Array System for Culturing Virus Infected Tumor Cells

Inhibition of the lytic cycle of Kaposi's sarcoma-associated herpesvirus by cohesin factors following de novo infection

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