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Adeno-associated virus type 2 interferes with early development of mouse embryos

Valérie Botquin^1,

angel Cid-Arregui^1,

¹ Deutsches Krebsforschungszentrum, FS Angewandte Tumorvirologie, Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany
and² Unité d'Oncologie Moléculaire, CNRS URA 1160, Institut Pasteur de Lille, 1 rue Calmette, F-59019 Lille Cedex, France

The human helper-dependent adeno-associated virus type 2 (AAV-2) has been shown to induce differentiation in various cell types in culture including pluripotent embryonic cells, in the absence of helper virus. To assess whether induction of differentiation may influence developmental processes we analysed the effect of AAV-2 on developing mouse embryos. In vitro infection of fertilized eggs induced arrest of development at the two-cell stage. Moreover, micro injection of AAV-2 DNA (comprising either the complete AAV-2 genome or a fragment containing the P5 promoter region) into one-cell embryos, blocked development at the morula stage. In vivo, AAV-2 infection of pregnant mice led to fetal death and early abortion. These results demonstrate that the human adeno-associated virus, which is thought to be non-pathogenic, can perturb embryonic development in mice. This may provide a suitable animal model system to further elucidate the biological significance of the recent detection of adeno-associated virus DNA in human abortion material.

Present address: Max-Delbrück-Centrum für Molekulare Medizin, Robert Rössle Str. 10, D-13122 Berlin-Buch, Germany.

Present address: European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.

Received 3 March 1994; accepted 19 May 1994.

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