Objective
In vitro studies has been carried out on the effect of parvoviruses on oncogenic transformation of mammalian cells. The parvovirus MVMP drastically inhibited in vitro transformation of mouse cells by the simian virus SV40, but was innocuous to normal parental cells. Such a sensitisation of transformants to parvoviral attack was detected with parvoviruses H-1 and MVMp in a series of human and murine fibroplasts and epithelial cells that were either transformed in vitro or derived from various carcinomas and sarcomas.
Parvoviruses can be used as selective agents to remove specific transformants from mixed populations of normal and transformed cells. In a model system consisting of cultures of SV40 transformed human kidney cells, infection with parvovirus H-1 led to the destruction of the transformants and to the emergence of a preexisting subpopulation of H-1 virus resistant cells that turned out to be variants failing to express the transformed phenotype.
The parvoviral attack against transformants could not be ascribed to a higher efficiency of virus uptake by these cells compared with their normal parents. In contrast, transformation correlated with a consistent stimulation of intracellular steps of the parvoviral life cycle, in particular deoxyribonucleic acid (DNA) amplification and expression of genes encoding 2 overlapping nonstructural (NS) proteins.
The formation of tumors in adult nude mice from transformed human mammary epithelial cells was drastically inhibited both after H-1 virus coinjection with tumoral cells and after a single delayed subcutaneous inoculation of H-1 virus at the site of cell implantation prior to tumor formation. Moreover, when injected intravenously in animals bearing performed tumors, H-1 virus was able to slow down the growth of the neoplasms and even in some cases to cause their complete regression. Viral infection was not accompanied by detectable deleterious side effect. This is the first demonstration that a parvovirus can suppress tumoral growth of implanted human cells in vivo. The occurrence of such a parvoviral surveillance in recipient animals that are deficient in immune antitumor mechanisms, together with the detection of H-1 virus DNA imprints in regressing tumors, are compatible with a role of oncolysis in the oncosuppressive activity of H-1 virus.
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
BRUXELLES
Belgium
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.