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.
- MeSH
- genetické vektory aplikace a dávkování genetika farmakokinetika MeSH
- HIV-1 genetika metabolismus MeSH
- HIV-2 genetika metabolismus MeSH
- kultivované buňky MeSH
- kvalitativní výzkum MeSH
- Lentivirus genetika metabolismus MeSH
- mozek metabolismus virologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- těhotenství MeSH
- transdukce genetická metody MeSH
- tropismus virů * MeSH
- virus opičí imunodeficience genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- Hepacivirus genetika izolace a purifikace MeSH
- hepatitida B * diagnóza epidemiologie virologie MeSH
- hepatitida C * diagnóza epidemiologie virologie MeSH
- HIV infekce * diagnóza epidemiologie virologie MeSH
- HIV-1 genetika izolace a purifikace MeSH
- HIV-2 genetika izolace a purifikace MeSH
- lidé MeSH
- virus hepatitidy B genetika izolace a purifikace MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
