title: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Xiu-Huai
authors.initials: XH
authors.lastname: Liu
authors.forename: Wenqin
authors.initials: W
authors.lastname: Xu
authors.forename: Jill
authors.initials: J
authors.lastname: Russ
authors.forename: Lee E
authors.initials: LE
authors.lastname: Eiden
authors.forename: Maribeth V
authors.initials: MV
authors.lastname: Eiden
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology; D004247:DNA / Q000378:metabolism; D016195:G2 Phase / Q000187:drug effects; D017988:Gammaretrovirus / Q000187:drug effects / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D058507:Host Specificity / Q000187:drug effects / Q000502:physiology*; D016086:Lentivirus / Q000187:drug effects / Q000235:genetics; D008938:Mitosis / Q000187:drug effects; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000821:virology*; D016716:PC12 Cells; D051381:Rats; D016196:S Phase / Q000187:drug effects; D044967:Serum; D014161:Transduction, Genetic; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D051020:bcl-X Protein; D049452:Green Fluorescent Proteins; D004247:DNA; D020932:Nerve Growth Factor