Dataset Information

The host range of gammaretroviruses and gammaretroviral vectors includes post-mitotic neural cells.

ABSTRACT:

Background

Gammaretroviruses and gammaretroviral vectors, in contrast to lentiviruses and lentiviral vectors, are reported to be restricted in their ability to infect growth-arrested cells. The block to this restriction has never been clearly defined. The original assessment of the inability of gammaretroviruses and gammaretroviral vectors to infect growth-arrested cells was carried out using established cell lines that had been growth-arrested by chemical means, and has been generalized to neurons, which are post-mitotic. We re-examined the capability of gammaretroviruses and their derived vectors to efficiently infect terminally differentiated neuroendocrine cells and primary cortical neurons, a target of both experimental and therapeutic interest.

Methodology/principal findings

Using GFP expression as a marker for infection, we determined that both growth-arrested (NGF-differentiated) rat pheochromocytoma cells (PC12 cells) and primary rat cortical neurons could be efficiently transduced, and maintained long-term protein expression, after exposure to murine leukemia virus (MLV) and MLV-based retroviral vectors. Terminally differentiated PC12 cells transduced with a gammaretroviral vector encoding the anti-apoptotic protein Bcl-xL were protected from cell death induced by withdrawal of nerve growth factor (NGF), demonstrating gammaretroviral vector-mediated delivery and expression of genes at levels sufficient for therapeutic effect in non-dividing cells. Post-mitotic rat cortical neurons were also shown to be susceptible to transduction by murine replication-competent gammaretroviruses and gammaretroviral vectors.

Conclusions/significance

These findings suggest that the host range of gammaretroviruses includes post-mitotic and other growth-arrested cells in mammals, and have implications for re-direction of gammaretroviral gene therapy to neurological disease.

SUBMITTER: Liu XH

PROVIDER: S-EPMC3065480 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Publications

The host range of gammaretroviruses and gammaretroviral vectors includes post-mitotic neural cells.

Liu Xiu-Huai XH Xu Wenqin W Russ Jill J Eiden Lee E LE Eiden Maribeth V MV

PloS one 20110328 3

<h4>Background</h4>Gammaretroviruses and gammaretroviral vectors, in contrast to lentiviruses and lentiviral vectors, are reported to be restricted in their ability to infect growth-arrested cells. The block to this restriction has never been clearly defined. The original assessment of the inability of gammaretroviruses and gammaretroviral vectors to infect growth-arrested cells was carried out using established cell lines that had been growth-arrested by chemical means, and has been generalized ...[more]

PMID: 21464894

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Dataset Information

The host range of gammaretroviruses and gammaretroviral vectors includes post-mitotic neural cells.

Background

Methodology/principal findings

Conclusions/significance

Publications

The host range of gammaretroviruses and gammaretroviral vectors includes post-mitotic neural cells.

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