Neoplastic Transformation-Associated Stimulation of the In Vitro Resolution of Concatemer Junction Fragments from Minute Virus of Mice DNA

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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Possible active origin of replication in the double stranded extended form of the left terminus of LuIII and its implication on the replication model of the parvovirus

Diffoot-Carlo

Vélez-Pérez

Jesús-Maldonado

2005

Virol J

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Background: The palindromic termini of parvoviruses have proven to play an essential role as origins of replication at different stages during the replication of their viral genome. Sequences from the left-end telomere of MVM form a functional origin on one side of the dimer replicative form intermediate. In contrast, the right-end origin can operate in its closed replicative form hairpin configuration or as a fully duplex linear sequence derived from either arm of a palindromic tetramer intermediate. To study the possibility that the LuIII left hairpin has a function in replication, comparable to that described for MVM, the replication of a minigenome containing two copies of the LuIII left terminus (LuIII Lt-Lt) was studied.

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Neoplastic Transformation-Associated Stimulation of the In Vitro Resolution of Concatemer Junction Fragments from Minute Virus of Mice DNA

Cited by 3 publications

References 45 publications

Proteins attached to viral genomes are multifunctional

Proteins attached to viral genomes are multifunctional

Augmented transgene expression in transformed cells using a parvoviral hybrid vector

Possible active origin of replication in the double stranded extended form of the left terminus of LuIII and its implication on the replication model of the parvovirus

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