Programmed killing of human cells by means of an inducible clone of parvoviral genes encoding non-structural proteins.

Caillet-Fauquet, Perrine; Perros, Manoussos; Brandenburger, Anne-Nicole; Spegelaere, Pierre; Rommelaere, Jean

doi:10.1002/j.1460-2075.1990.tb07491.x

Cited by 169 publications

(130 citation statements)

References 33 publications

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“…13 The NS1 protein is cytotoxic and contributes to the lytic growth of parvoviruses. 16,17 Characteristic features of apoptosis were observed after cell infection with parvovirus H1 and the related human parvovirus B19. 18 ± 21 Interestingly, the parvoviruses minute virus of mice and H1 virus preferentially replicate in and kill oncogene -transformed and tumorderived cells in culture.…”

mentioning

confidence: 99%

Effective infection, apoptotic cell killing and gene transfer of human hepatoma cells but not primary hepatocytes by parvovirus H1 and derived vectors

Moehler¹,

Blechacz

Weiskopf³

et al. 2001

Cancer Gene Ther

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Autonomous parvoviruses preferentially replicate in and kill in vitro ± transformed cells and reduce the incidence of spontaneous and implanted tumors in animals. Because of these natural oncotropic and oncolytic properties, parvoviruses deserve to be considered as potential antitumor vectors. Here, we assessed whether parvovirus H1 is able to kill human hepatoma cells by induction of apoptosis but spares primary human liver cells, and whether the former cells can efficiently be transduced by H1 virus ± based vectors. Cell death, infectivity, and transgene transduction were investigated in Hep3B, HepG2, and Huh7 cells and in primary human hepatocytes with natural and recombinant H1 virus. All hepatoma cells were susceptible to H1 virus ± induced cytolyis. Cell death correlated with H1 virus DNA replication, nonstructural protein expression, and with morphological features of apoptosis. H1 virus ± induced apoptosis was more pronounced in p53 -deleted Hep3B and p53 -mutated Huh7 cells than in HepG2 cells which express wild -type p53. In Hep3B cells, apoptosis was partially inhibited by DEVD -CHO, a caspase -3 inhibitor. In contrast, H1 virus ± infected primary hepatocytes were neither positive for nonstructural protein expression nor susceptible to H1 virus ± induced killing. Infection with a recombinant parvovirus vector carrying the luciferase gene under control of parvovirus promoter P38 led to higher transgene activities in hepatoma cells than in the hepatocytes. Taken together, H1 virus kills human hepatoma cells at low virus multiplicity but not primary hepatocytes. Thus, recombinant H1 viruses carrying antitumor transgenes may be considered as potential therapeutic options for the treatment of hepatocellular carcinomas. Cancer Gene Therapy ( 2001 ) 8, 158 ± 167

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mentioning

confidence: 99%

Effective infection, apoptotic cell killing and gene transfer of human hepatoma cells but not primary hepatocytes by parvovirus H1 and derived vectors

Moehler¹,

Blechacz

Weiskopf³

et al. 2001

Cancer Gene Ther

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“…18,19 The NS proteins, moreover, exert cytotoxic activity in transformed cells. 20,21 These various observations led to the idea that one might achieve tumorselective expression of a foreign gene by means of a parvoviral vector obtained by replacing the capsid protein genes with the foreign gene. 10 Vectors based on MVMp were constructed, expressing 46 The resulting recombinant virus stocks were purified and concentrated as described.…”

mentioning

confidence: 99%

Tumor-selective gene transduction and cell killing with an oncotropic autonomous parvovirus-based vector

Dupont¹,

Avalosse²,

Karim³

et al. 2000

Gene Ther

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A recombinant MVMp of the fibrotropic strain of minute virus of mice (MVMp) expressing the chloramphenicol acetyltransferase reporter gene was used to infect a series of biologically relevant cultured cells, normal or tumor-derived, including normal melanocytes versus melanoma cells, normal mammary epithelial cells versus breast adenocarcinoma cells, and normal neurons or astrocytes versus glioma cells. As a reference cell system we used normal human fibroblasts versus the SV40-transformed fibroblast cell line NB324K. After infection, we observed good expression of the reporter gene in the different tumor cell types, but only poor expression if any in the corresponding normal cells. We also constructed a recombinant MVMp expressing the green fluorescent protein reporter gene and assessed by flow cytometry the efficiency of gene transduction into the different target cells. At a multiplicity of infection of 30, we observed

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“…The basis of oncoselectivity of autonomous parvoviruses MVM and H1 is their preferred replication in proliferating cells, 90 the enhanced cytotoxicity in transformed cells [64][65][66]91 and the increased p4 promoter activity in proliferating and transformed cells. 18 The hybrid vector analyzed here, with part of the H1 left end terminal palindrome, the p4 promoter and the ns1 gene is not replication competent (Figure 2b).…”

Section: Discussionmentioning

confidence: 99%

Augmented transgene expression in transformed cells using a parvoviral hybrid vector

et al. 2008

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Autonomous parvoviruses possess an intrinsic oncotropism based on viral genetic elements controlling gene expression and genome replication. We constructed a hybrid vector consisting of the H1 parvovirus-derived expression cassette comprising the p4 promoter, the ns1 gene and the p38 promoter flanked by the adeno-associated viruses 2 (AAV2) inverted terminal repeats and packaged into AAV2 capsids. Gene transduction using this vector could be stimulated by coinfection with adenovirus, by irradiation or treatment with genotoxic agents, similar to standard AAV2 vectors. However, the latter were in most cases less efficient in gene transduction than the hybrid vector. With the new vector, tumor cell-selective increase in transgene expression was observed in pairs of transformed and non-transformed cells, leading to selective killing of the transformed cells after expression of a prodrug-converting enzyme. Preferential gene expression in tumor versus normal liver tissue was also observed in vivo in a syngeneic rat model. Comparative transduction of a panel of different tumor cell lines with the H1 and the H1/AAV hybrid vector showed a preference of each vector for distinct cell types, probably reflecting the dependence of the viral tropism on capsid determinants.

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Programmed killing of human cells by means of an inducible clone of parvoviral genes encoding non-structural proteins.

Cited by 169 publications

References 33 publications

Effective infection, apoptotic cell killing and gene transfer of human hepatoma cells but not primary hepatocytes by parvovirus H1 and derived vectors

Effective infection, apoptotic cell killing and gene transfer of human hepatoma cells but not primary hepatocytes by parvovirus H1 and derived vectors

Tumor-selective gene transduction and cell killing with an oncotropic autonomous parvovirus-based vector

Augmented transgene expression in transformed cells using a parvoviral hybrid vector

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