Persistence of Selectable Herpesvirus Saimiri in Various Human Haematopoietic and Epithelial Cell Lines

Simmer, B.; Alt, Michael; Buckreus, I.; Berthold, S.; Fleckenstein, Bernhard; Platzer, E.; Grassmann, Ralph

doi:10.1099/0022-1317-72-8-1953

Cited by 54 publications

(65 citation statements)

References 39 publications

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“…We and others have previously demonstrated that HVS can infect a wide range of human cell lines and that the HVS genome persists in a latent episomal state that segregates to progeny upon cell division allowing longterm in vitro gene expression. [7][8][9][10][11] More recently, we demonstrated that the HVS genome can persist in human tumor xenografts derived from ex vivo HVS-infected human carcinoma cells. 12,19 Our previous work has demonstrated that HVS-based vectors (expressing GFP) persisted as nonintegrated episomes in vivo, and provided long-term transgene expression with no evidence of promoter silencing, viral spread or cytopathic effects.…”

Section: Discussionmentioning

confidence: 99%

“…The lines represented cells from the epithelium and connective tissues as well as from hematopoietic lineages. 6,7 Viral episomes were still observed within infected cells long after selective pressure was removed. 6,7 However, a number of these cell lines produced infectious virus.…”

mentioning

confidence: 99%

“…6,7 Viral episomes were still observed within infected cells long after selective pressure was removed. 6,7 However, a number of these cell lines produced infectious virus. 6,7 More recently, HVS recombinants have been produced expressing beta-galactosidase or enhanced green fluorescence protein (EGFP), and the neomycin resistance genes under the control of the IE CMV and SV40 promoters, respectively.…”

mentioning

confidence: 99%

“…6,7 However, a number of these cell lines produced infectious virus. 6,7 More recently, HVS recombinants have been produced expressing beta-galactosidase or enhanced green fluorescence protein (EGFP), and the neomycin resistance genes under the control of the IE CMV and SV40 promoters, respectively. [8][9][10] Analysis using these viruses, which can be grown to a high titer in the permissive owl monkey kidney (OMK) cell line, has demonstrated infection of a wide variety of human carcinoma cell lines at approaching 100% efficiency.…”

mentioning

confidence: 99%

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Efficient infection and persistence of a herpesvirus saimiri-based gene delivery vector into human tumor xenografts and multicellular spheroid cultures

et al. 2004

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Herpesvirus saimiri (HVS) has the ability to infect a variety of human cell lines and establish a persistent infection by virtue of episomal maintenance. Moreover, the viral episome provides sustained expression of a heterologous transgene. HVS-based vectors can also persist for a long term in tumor xenografts generated from HVS-infected human carcinoma cell lines. The viral episome remains latent within the xenograft allowing long-term transgene expression. These properties, in addition to its ability to incorporate large amounts of heterologous DNA, make HVS an attractive potential gene delivery vector. Here we report on the further evaluation of such HVS-based vectors. We demonstrate for the first time that HVS can efficiently infect solid tumor xenografts derived from a variety of human carcinoma cells via direct intratumoral injections. Furthermore, HVS can efficiently infect spheroid cultures, a three-dimensional cell culture system that closely resembles a tumor. Upon infection of both the tumor xenografts and spheroid cultures, HVS-based vectors can establish a persistent episomal infection within the tumor xenograft allowing expression of a heterologous transgene. These results suggest that HVS-based vectors may be suitable for cancer gene therapy applications.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Efficient infection and persistence of a herpesvirus saimiri-based gene delivery vector into human tumor xenografts and multicellular spheroid cultures

et al. 2004

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“…18,19 Earlier publications have demonstrated that a selectable HVS has the ability to persist in a variety of human cell lines for long periods of time, apparently without the production of infectious progeny. 20,21 In this report, we describe our findings using a nontransforming wild-type (wt) virus carrying the enhanced green fluorescent protein (EGFP) and neomycin resistance (neo r ) marker genes. Using this vector, we have investigated tropism for specific lineages of hemopoietic cells, allowing us to elucidate potential strategies for clinical applications.…”

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confidence: 99%

A herpesvirus saimiri-based gene therapy vector with potential for use in cancer immunotherapy

et al. 2000

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The herpesvirus saimiri (HVS) genome has the capacity to incorporate large amounts of heterologous DNA and can be maintained episomally in many different human cell types. To evaluate the efficacy of HVS-mediated gene transfer into human hemopoietic cells, we investigated the ability of an HVS-based construct, carrying the enhanced green fluorescent protein (EGFP) and neomycin resistance genes, to transduce a variety of human hemopoietic cell lines and primary CD34 ϩ cells. As measured by flow cytometry, the numbers of EGFP ϩ cells at 2 days postinfection differed between various cell types ranging, from 1.3% for KG1 cells to 56.8% for THP-1 cells. In addition, the expression of EGFP in Jurkat cells was retained at Ͼ95% per round of cell division over a period of 6 weeks (comparable with Epstein-Barr virus-derived gene therapy systems). Although the virus was not specifically disabled, no lytic viral mRNAs could be detected in transduced Jurkat cells, and infectious virus could not be detected by sensitive virus recovery assay. We also describe a simple centrifugation method that increases the efficiency of transduction by Ͼ100% in some cases and may be generally applicable to other herpesvirus-based vectors for ex vivo gene delivery. Using this technique, we were able to demonstrate a tropism for CD34 ϩ /CD14 ϩ cells, transducing 30% of the population. These cells are known to give rise to dendritic cells (the most potent of the antigen-presenting cells), suggesting that the vector could be used to deliver DNA sequences encoding tumor antigens for cancer immunotherapy.

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Assessment of Herpesvirus saimiri as a potential human gene therapy vector

et al. 1999

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Herpesvirus saimiri has characteristics that make it amenable to development as a gene therapy vector. The viral genome is thought to be capable of accommodating large quantities of heterologous DNA while the virus itself can infect many different cell types. Virus infection has been shown in many cases to be persistent by virtue of episomal maintenance in the target cell. In this article we examine the ability of nonselectable recombinant viruses expressing the beta-galactosidase gene product to infect a variety of human cells and demonstrate that this virus could be developed as an alternative hematopoietic stem cell gene therapy vector. In contrast to earlier observations, we demonstrate by a number of methods that the virus has the ability to replicate in many human cell types, suggesting the need for the development of a disabled virus for use as a gene therapy vector.

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Persistence of Selectable Herpesvirus Saimiri in Various Human Haematopoietic and Epithelial Cell Lines

Cited by 54 publications

References 39 publications

Efficient infection and persistence of a herpesvirus saimiri-based gene delivery vector into human tumor xenografts and multicellular spheroid cultures

Efficient infection and persistence of a herpesvirus saimiri-based gene delivery vector into human tumor xenografts and multicellular spheroid cultures

A herpesvirus saimiri-based gene therapy vector with potential for use in cancer immunotherapy

Assessment of Herpesvirus saimiri as a potential human gene therapy vector

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