Analysis of Gene Expression in a Human Cell Line Stably Transduced with Herpesvirus Saimiri

Hall, Kersten T.; Giles, Mathew; Goodwin, Delyth J.; Calderwood, Michael A.; Carr, Ian; Stevenson, Alexander J.; Markham, Alex F.; Whitehouse, Adrian

doi:10.1128/jvi.74.16.7331-7337.2000

Cited by 31 publications

(58 citation statements)

References 60 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%

“…Specific amplification of the ORF 73, a gene latently expressed in human carcinoma cell lines, 11 was performed. In addition, as a suitable control, GAPDH DNA was detected in all samples, indicating that sufficient amounts of DNA had been extracted from each tissue.…”

Section: Efficient Infection Of Human Tumor Xenografts Via Direct Intmentioning

confidence: 99%

“…The presence of lytic gene expression is not surprising, as we have previously observed a very low level of spontaneous replication in stably transduced lung carcinoma cell lines and human tumor xenografts. 11,12,19 HVS is maintained as a circular episome in human tumor xenografts after direct intratumoral injections…”

Section: Hvs Can Establish a Latent Infection In Human Tumor Xenografmentioning

confidence: 99%

“…11,12,19 To verify the existence of HVS genomes in a circular, nonintegrated episomal form in human tumor xenografts after direct injection, viral DNA conformation was analyzed by Gardella gel electrophoresis and Southern blot analysis. [23][24][25] An HVS-transformed T-cell line from cottontop tamarin monkeys, 16,26 which contains HVS as a circular nonintegrated episome, was also analyzed as a suitable control.…”

Section: Hvs Can Establish a Latent Infection In Human Tumor Xenografmentioning

confidence: 99%

“…11,12 The long-term presence of the HVS episome is believed not to affect cell growth, as the in vitro growth rates of uninfected human carcinoma cells and cells persistently infected with HVS-GFP showed no significant difference in the doubling time of the cell populations. This suggests that the maintenance of the HVS episome does not disrupt the growth machinery of human cancer cells in vitro.…”

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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%

Section: Efficient Infection Of Human Tumor Xenografts Via Direct Intmentioning

confidence: 99%

Section: Hvs Can Establish a Latent Infection In Human Tumor Xenografmentioning

confidence: 99%

Section: Hvs Can Establish a Latent Infection In Human Tumor Xenografmentioning

confidence: 99%

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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

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Cell transformation byHerpesvirus saimiri

Tsygankov

2004

Journal Cellular Physiology

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Herpesvirus saimiri (Saimiriine herpesvirus-2), a g2-herpesvirus (rhadinovirus) of non-human primates, causes T-lymphoproliferative diseases in susceptible organisms and transforms human and non-human T lymphocytes to continuous growth in vitro in the absence of stimulation. T cells transformed by H. saimiri retain many characteristics of intact T lymphocytes, such as the sensitivity to interleukin-2 and the ability to recognize the corresponding antigens. As a result, H. saimiri is widely used in immunobiology for immortalization of various difficult-to-obtain and/or -to-maintain T cells in order to obtain useful experimental models. In particular, H. saimiri-transformed human T cells are highly susceptible to infection with HIV-1 and -2. This makes them a convenient tool for propagation of poorly replicating strains of HIV, including primary clinical isolates. Therefore, the mechanisms mediating transformation of T cells by H. saimiri are of considerable interest. A single transformation-associated protein, StpA or StpB, mediates cell transformation by H. saimiri strains of group A or B, respectively. Strains of group C, which exhibit the highest oncogenic potential, have two proteins involved in transformation-StpC and Tip. Both proteins have been shown to dramatically affect signal transduction pathways leading to the activation of crucial transcription factors. This review is focused on the biological effects and molecular mechanisms of action of proteins involved in H. saimiri-dependent transformation.

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Herpesvirus Saimiri Pathogenicity Enhanced by Thymidine Kinase of Herpes Simplex Virus

et al. 2000

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Herpesvirus saimiri can be used as an efficient gene expression vector for human T lymphocytes and thus may allow applications in experimental leukemia therapy. We constructed recombinant viruses for the functional expression of the thymidine kinase (TK) of herpes simplex virus type 1 (HSV) as a suicide gene. These viruses reliably allowed the targeted elimination of transduced nonpermissive human T cells in vitro after the administration of ganciclovir. To test the reliability of this function under the most stringent permissive conditions, in this study we analyzed the influence of the prodrugs ganciclovir and acyclovir in common marmosets on the acute leukemogenesis induced by either wild-type herpesvirus saimiri C488 or by a recombinant derivative expressing TK of HSV. Antiviral drug treatment did not influence the rapid development of acute disease. In contrast, the presence of the HSV tk gene resulted in a faster disease progression. In addition, HSV TK-expressing viruses showed faster replication than wild-type virus in culture at low serum concentrations. Thus, HSV TK accelerates the replication of herpesvirus saimiri and enhances its pathogenicity. This should be generally considered when HSV TK is applied as a transgene in replication-competent DNA virus vectors for gene therapy.

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Analysis of Gene Expression in a Human Cell Line Stably Transduced with Herpesvirus Saimiri

Cited by 31 publications

References 60 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

Cell transformation byHerpesvirus saimiri

Herpesvirus Saimiri Pathogenicity Enhanced by Thymidine Kinase of Herpes Simplex Virus

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