Modulation of the cellular phenotype by integrated adeno-associated virus

Winocour, Ernest; Puzis, Leopold; Etkin, Sara; Koch, T; Danovitch, Bernard; Mendelson, Ella; Shauliana, Eitan; Karby, Shulamit; Lavi, Sara

doi:10.1016/0042-6822(92)91218-j

Cited by 25 publications

(13 citation statements)

References 47 publications

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“…In a series of experiments in which Chinese hamster embryo cells were latently infected by DNA, it was noted that latency was associated with increased sensitivity to UV-irradiation and the ability of UV-irradiation to induce gene amplification was decreased (50). Although such effects could be the result of insertional mutagenesis, there is a strong suspicion that the effects are the consequence of rep gene expression (although in the case cited immediately above, there was not a strict correlation between the amount of Rep detected and the magnitude of the phenotypic effect).…”

Section: Latent Infectionmentioning

confidence: 99%

The cryptic life style of adenoassociated virus

1995

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Although 80-90% of adults are seropositive for antibodies against the human parvovirus adeno-associated virus (AAV), infection has not been associated with either symptoms or disease. In cell culture, AAV infection is not productive unless there is a coinfection with a helper virus, either adenovirus or any type of herpes virus; in the absence of a helper virus coinfection the viral genome is integrated into the genome, usually at a specific site on chromosome 19q13.3-qter. The integrated genome can be activated and rescued by subsequent super infection by a helper virus. The high frequency of site-specific integration by AAV and the lack of associated disease have encouraged the use of AAV as a vector for gene therapy. This review will focus on the molecular mechanisms involved in the establishment of, and rescue from, the latent state and their relevance to use of AAV as a vector.

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Section: Latent Infectionmentioning

confidence: 99%

The cryptic life style of adenoassociated virus

1995

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“…AAV is unique in that it is the first example of an exogenous DNA which has been demonstrated to preferentially integrate at a specific site in the human genome, on the q arm of chromosome 19 (KOTIN et al 1990(KOTIN et al , 1991(KOTIN et al , 1992SAMULSKI et al 1991;SAMULSKI 1993). Studies of cells in culture latently infected by AA V have demonstrated that there are effects on the cellular phenotype which are usually subtle and affect the ability of the cell to respond to stress (YALKINOGLU et al 1988;Y AKOBSON et al 1987Y AKOBSON et al , 1989BANTEL-SCHAAL and STOHR 1992;BANTEL-SCHAAL 1991;WINOCOUR et al 1988WINOCOUR et al , 1992WALl and SCHLEHOFER 1992;WALl et al 1992; KLEIN-BAUERNSCHMITT et al 1992).…”

mentioning

confidence: 95%

Biology of Adeno-associated Virus

Berns

Giraud

1996

Current Topics in Microbiology and Immunology

198

173

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“…The hypothesis of a role of AAV-2 DNA is supported by our finding that micro injection of non-coding fragments of AAV-2 D N A into fertilized oocytes led to an early arrest of embryonic development. Since integration of AAV-2 has been reported to modify the biological properties of cells (Walz & Schlehofer, 1992;Winocour et al, 1992) a possible mechanism for disturbance of embryonic growth might be the integration of AAV-2 sequences into gene(s) critical for development. Another possibility may be an interaction of cellular regulatory factors with AAV-2 D N A leading to inappropriate binding or a competition for factors important in embryonic development.…”

Section: Discussionmentioning

confidence: 99%

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

Botquin

Cid-Arregui

Schlehofer

1994

Journal of General Virology

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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 twocell stage. Moreover, micro injection of AAV-2 DNA (comprising either the complete AAV-2 genome or a fragment containing the P5 promoter region) into onecell 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.

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Modulation of the cellular phenotype by integrated adeno-associated virus

Cited by 25 publications

References 47 publications

The cryptic life style of adenoassociated virus

The cryptic life style of adenoassociated virus

Biology of Adeno-associated Virus

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

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