Cooperation of oncogenes in cell transformation and sensitization to killing by the parvovirus minute virus of mice

Legrand, Colette; Mousset, Suzanne; Salomé, Nathalie; Rommelaere, Jean

doi:10.1099/0022-1317-73-8-2003

Cited by 12 publications

(7 citation statements)

References 26 publications

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“…These cells were grown in minimal essential medium supplemented with 5% fetal calf serum (Boehringer). The FR4 cell line, a subclone of the FR3T3 established line of Fisher rat cells (33), was described elsewhere (15). FREJ4 (37) and FRMTT4 (24) are FR3T3 cell derivatives transformed by the c-Ha-ras and polyomavirus middle T oncogenes, respectively.…”

Section: Materills and Methodsmentioning

confidence: 99%

“…It is noteworthy that the accomplishment of a complete viral lytic cycle is not necessary to kill transformed cells (13) and, conversely, that the production of infectious viral particles can be dissociated from cell killing (31). It has been shown that oncogenic transformation of established rat cells correlates with a parallel increase in their sensitivity to the cytocidal effect of MVMp and their capacity to synthesize the parvovirus NS proteins (6,15,30,37). This and other indirect evidence (4,21,26) suggested that NS proteins may have a cytotoxic activity.…”

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confidence: 99%

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The cytotoxicity of the autonomous parvovirus minute virus of mice nonstructural proteins in FR3T3 rat cells depends on oncogene expression

Mousset

Ouadrhiri

Caillet-Fauquet

et al. 1994

J Virol

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The nonstructural (NS) proteins of the autonomous parvovirus minute virus of mice are involved in viral DNA replication and in the regulation of homologous and heterologous promoters. Moreover, NS products have proved to be cytotoxic, especially for transformed cells. We show here that intracellular accumulation of NS products is not sufficient to kill rat fibroblasts from the established cell line FR3T3, which is phenotypically normal in several respects. FRNS cell lines were obtained by stable transfection of FR3T3 cells by a vector carrying the NS genes under the control of the hormone-inducible long terminal repeat promoter of the mouse mammary tumor virus. In the presence of dexamethasone, the NS proteins were synthesized without associated cell death. Transformation of FRNS cells with the c-Ha-ras oncogene or polyomavirus oncogenes had little effect on their capacity for NS induction, as measured at both concentration and transactivating activity levels, yet the transformants were now dying within a few days in the presence of the inducer. The same results were obtained with cells stably transfected by a vector expressing the NS1 product alone, suggesting that in this system there is no cooperation between NS1 and NS2 for maximal cytopathic effect. Cell mortality after NS protein induction was quantitatively related to the yield of oncogene expression, while NS-1 was not limiting in this respect. Our results show that the NS1 protein is not lethal unless cellular factors that may depend on oncogene expression trigger its cytotoxicity.

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Section: Materills and Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

The cytotoxicity of the autonomous parvovirus minute virus of mice nonstructural proteins in FR3T3 rat cells depends on oncogene expression

Mousset

Ouadrhiri

Caillet-Fauquet

et al. 1994

J Virol

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“…Firstly, these viruses are naturally S-phase dependent, so that they preferentially target host cell populations that are proliferating, while sparing those that are not. The rodent parvoviruses are also markedly oncoselective, displaying enhanced fitness and toxicity in many human cancer cell lines compared to their untransformed counterparts, although they show variable tropism between tumor types (Chen et al, 1986; Chen et al, 1989; Cornelis et al, 2004; Dupont et al, 2000; Guetta et al, 1990; Legrand et al, 1992; Mousset et al, 1994; Rommelaere and Cornelis, 1991; Van Hille et al, 1989). They show potent oncosuppressive properties in many in vivo models, including syngeneic mouse tumor models and human xenografts transplanted into immunocompromised animals (Dupressoir et al, 1989; Faisst et al, 1998; Raykov et al, 2007; Rommelaere and Cornelis, 1991; Shi et al, 1997; Toolan, 1967; Toolan et al, 1982), and can also induce both curative and protective immune responses in some immunocompetent rodent tumor models (Guetta et al, 1986; Geletneky et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

The parvoviral capsid controls an intracellular phase of infection essential for efficient killing of stepwise-transformed human fibroblasts

Paglino

Tattersall

2011

Virology

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Members of the rodent subgroup of the genus Parvovirus exhibit lytic replication and spread in many human tumor cells and are therefore attractive candidates for oncolytic virotherapy. However, the significant variation in tumor tropism observed for these viruses remains largely unexplained. We report here that LuIII kills BJ-ELR ‘stepwise-transformed’ human fibroblasts efficiently, while MVM does not. Using viral chimeras, we mapped this property to the LuIII capsid gene, VP2, which is necessary and sufficient to confer the killer phenotype on MVM. LuIII VP2 facilitates a post-entry, pre-DNA-amplification step early in the life cycle, suggesting the existence of an intracellular moiety whose efficient interaction with the incoming capsid shell is critical to infection. Thus targeting of human cancers of different tissue-type origins will require use of parvoviruses with capsids that effectively make this critical interaction.

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“…The Parvoviridae are a family of small (20-25 nm), icosahedral, non-enveloped viruses, unique in that they package a linear single-stranded DNA genome. Several members of the genus Parvovirus, such as Minute Virus of Mice (MVM), LuIII and H-1, are known to be inherently oncoselective, demonstrating enhanced fitness and toxicity in many transformed human cell types, compared to their normal counterparts, under the same growth conditions in vitro (Rommelaere and Cornelis, 1991;Legrand et al, 1992;Deleu et al, 1999;Cornelis et al, 2005). In vivo, wildtype parvovirus infection can suppress the development of certain tumors, for example, H1 suppression of HeLa tumor growth in SCID mice (Rommelaere and Cornelis, 1991;Faisst et al, 1998;Cornelis et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Exploring the contribution of distal P4 promoter elements to the oncoselectivity of Minute Virus of Mice

Paglino¹,

Burnett²,

Tattersall³

2007

Virology

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Minute Virus of Mice (MVM) shares inherent oncotropic properties with other members of the genus Parvovirus. Two elements responsible, at least in part, for this oncoselectivity have been mapped to an Ets1 binding site adjacent to the P4 TATA box of the initiating promoter, P4, and to a more distal cyclic AMP responsive element (CRE), located within the telomeric hairpin stem. Here the CRE overlaps one half-site for the binding of parvoviral initiation factor (PIF), which is essential for viral DNA replication. We used a degenerate oligonucleotide selection approach to show that CRE binding protein (CREB) selects the sequence ACGTCAC within this context, rather than its more generally accepted palindromic TGACGTCA recognition site. We have developed strategies for manipulating these sequences directly within the left-end palindrome of the MVM infectious clone and used them to clone mutants whose CRE either matches the symmetric consensus sequence or is scrambled, or in which the PIF binding site is incrementally weakened with respect to the CRE. The panel of mutants were tested for fitness relative to wildtype in normal murine fibroblasts A9 or transformed human fibroblasts 324 K, through multiple rounds of growth in co-infected cultures, using a differential real-time quantitative PCR assay. We confirmed that inactivating the CRE substantially abrogates oncoselectivity, but found that improving its fit to the palindromic consensus is somewhat debilitating in either cell type. We also confirmed that reducing the PIF half-site spacing by one basepair enhances oncoselectivity, but found that a further basepair deletion significantly reduces this effect.

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Cooperation of oncogenes in cell transformation and sensitization to killing by the parvovirus minute virus of mice

Cited by 12 publications

References 26 publications

The cytotoxicity of the autonomous parvovirus minute virus of mice nonstructural proteins in FR3T3 rat cells depends on oncogene expression

The cytotoxicity of the autonomous parvovirus minute virus of mice nonstructural proteins in FR3T3 rat cells depends on oncogene expression

The parvoviral capsid controls an intracellular phase of infection essential for efficient killing of stepwise-transformed human fibroblasts

Exploring the contribution of distal P4 promoter elements to the oncoselectivity of Minute Virus of Mice

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