Tropism, intracerebral distribution, and transduction efficiency of HIV- and SIV-based lentiviral vectors after injection into the mouse brain: a qualitative and quantitative in vivo study
| العنوان: | Tropism, intracerebral distribution, and transduction efficiency of HIV- and SIV-based lentiviral vectors after injection into the mouse brain: a qualitative and quantitative in vivo study |
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| المؤلفون: | Matthias Renner, Silke Schüle, Juraj Hlavatý, Zbyněk Tonar, Helga Petznek, Sylvia Panitz, Kirsti Witter, Rudolf Moldzio, Björn-Philipp Kloke, Matthias Schweizer |
| المصدر: | Histochemistry and Cell Biology |
| بيانات النشر: | Springer Berlin Heidelberg, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Histology, viruses, Stereology, Population, Genetic Vectors, EGFP, Biology, Vpr, Viral vector, Double immunofluorescence, 03 medical and health sciences, Transduction (genetics), Vpx, Mice, Pregnancy, Transduction, Genetic, medicine, Animals, education, Molecular Biology, Gene transfer, Tropism, Cells, Cultured, Qualitative Research, education.field_of_study, Original Paper, Lentivirus, virus diseases, Brain, Cell Biology, Molecular biology, Olfactory bulb, Mice, Inbred C57BL, Medical Laboratory Technology, Viral Tropism, 030104 developmental biology, medicine.anatomical_structure, nervous system, HIV-2, Tissue tropism, HIV-1, Female, Simian Immunodeficiency Virus, Neuron, Cellular Tropism |
| الوصف: | Lentiviruses are suitable to transfer potential therapeutic genes into non-replicating cells such as neurons, but systematic in vivo studies on transduction of neural cells within the complete brain are missing. We analysed the distribution of transduced cells with respect to brain structure, virus tropism, numbers of transduced neurons per brain, and influence of the Vpx or Vpr accessory proteins after injection of vectors based on SIVsmmPBj, HIV-2, and HIV-1 lentiviruses into the right striatum of the mouse brain. Transduced cells were found ipsilaterally around the injection canal, in corpus striatum and along corpus callosum, irrespective of the vector type. All vectors except HIV-2SEW transduced also single cells in the olfactory bulb, hippocampus, and cerebellum. Vector HIV-2SEW was the most neuron specific. However, vectors PBjSEW and HIV-1SEW transduced more neurons per brain (means 41,299 and 32,309) than HIV-2SEW (16,102). In the presence of Vpx/Vpr proteins, HIV-2SEW(Vpx) and HIV-1SEW(Vpr) showed higher overall transduction efficiencies (30,696 and 27,947 neurons per brain) than PBjSEW(Vpx) (6636). The distances of transduced cells from the injection canal did not differ among the viruses but correlated positively with the numbers of transduced neurons. The presence of Vpx/Vpr did not increase the numbers of transduced neurons. Parental virus type and the vector equipment seem to influence cellular tropism and transduction efficiency. Thus, precision of injection and choice of virus pseudotype are not sufficient when targeted lentiviral vector transduction of a defined brain cell population is required. Electronic supplementary material The online version of this article (doi:10.1007/s00418-017-1569-1) contains supplementary material, which is available to authorized users. |
| اللغة: | English |
| تدمد: | 1432-119X 0948-6143 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::83109cc281da022814d5722376bbdd25Test http://europepmc.org/articles/PMC5539277Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....83109cc281da022814d5722376bbdd25 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1432119X 09486143 |
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