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
| Autor: | Matthias Renner, Silke Schüle, Juraj Hlavatý, Zbyněk Tonar, Helga Petznek, Sylvia Panitz, Kirsti Witter, Rudolf Moldzio, Björn-Philipp Kloke, Matthias Schweizer |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
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 |
| Zdroj: | Histochemistry and Cell Biology |
| ISSN: | 1432-119X 0948-6143 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|