Differentiated neuroprogenitor cells incubated with human or canine adenovirus, or lentiviral vectors have distinct transcriptome profiles
Piersanti, Stefania (Università di Roma. Dipartimento di Biologia e Biotecnologie "Charles Darwin" (Roma, Itàlia))
Astrologo, Letizia (Università di Roma. Dipartimento di Biologia e Biotecnologie "Charles Darwin" (Roma, Itàlia))
Licursi, Valerio (Università di Roma. Dipartimento di Biologia e Biotecnologie "Charles Darwin" (Roma, Itàlia))
Costa, Rossella (Università di Roma. Dipartimento di Biologia e Biotecnologie "Charles Darwin" (Roma, Itàlia))
Roncaglia, Enrica (Università degli Studi di Modena e Reggio Emilia. Dipartimento di Scienze Biomediche (Modena, Itàlia))
Gennetier, Aurelie (Institut de Génétique Moléculaire (Montpellier, França))
Ibanes, Sandy (Institut de Génétique Moléculaire (Montpellier, França))
Chillón Rodríguez, Miguel (Istituto Pasteur. Fondazione Cenci Bolognetti (Roma, Itàlia))
Negri, Rodolfo (Università di Roma. Dipartimento di Biologia e Biotecnologie "Charles Darwin" (Roma, Itàlia))
Tagliafico, Enrico (Università degli Studi di Modena e Reggio Emilia. Dipartimento di Scienze Biomediche (Modena, Itàlia))
Kremer, Eric J. (Institut de Génétique Moléculaire (Montpellier, França))

Fecha:	2013
Resumen:	Several studies have demonstrated the potential for vector-mediated gene transfer to the brain. Helper-dependent (HD) human (HAd) and canine (CAV-2) adenovirus, and VSV-G-pseudotyped self-inactivating HIV-1 vectors (LV) effectively transduce human brain cells and their toxicity has been partly analysed. However, their effect on the brain homeostasis is far from fully defined, especially because of the complexity of the central nervous system (CNS). With the goal of dissecting the toxicogenomic signatures of the three vectors for human neurons, we transduced a bona fide human neuronal system with HD-HAd, HD-CAV-2 and LV. We analysed the transcriptional response of more than 47,000 transcripts using gene chips. Chip data showed that HD-CAV-2 and LV vectors activated the innate arm of the immune response, including Toll-like receptors and hyaluronan circuits. LV vector also induced an IFN response. Moreover, HD-CAV-2 and LV vectors affected DNA damage pathways - but in opposite directions - suggesting a differential response of the p53 and ATM pathways to the vector genomes. As a general response to the vectors, human neurons activated pro-survival genes and neuron morphogenesis, presumably with the goal of re-establishing homeostasis. These data are complementary to in vivo studies on brain vector toxicity and allow a better understanding of the impact of viral vectors on human neurons, and mechanistic approaches to improve the therapeutic impact of brain-directed gene transfer.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; Versió publicada
Materia:	Immune response ; Cell differentiation ; Gene expression ; Central nervous system ; Viral vectors
Publicado en:	PloS one, Vol. 8, Issue 7 (July 2013) , p. e69808, ISSN 1932-6203

DOI: 10.1371/journal.pone.0069808
PMID: 23922808

14 p, 6.9 MB

El registro aparece en las colecciones:
Artículos > Artículos publicados