Targeted Transduction Patterns in the Mouse Brain by Lentivirus Vectors Pseudotyped with VSV, Ebola, Mokola, LCMV, or MuLV Envelope Proteins

Lentiviral vectors have proven to be promising tools for transduction of central nervous system (CNS) cells in vivo and in vitro. In this study, CNS transduction patterns of lentiviral vectors pseudotyped with envelope glycoproteins from Ebola virus, murine leukemia virus (MuLV), lymphocytic choriomeningitis virus (LCMV), or the rabies-related Mokola virus were compared to a vector pseudotyped with the vesicular stomatitis virus glycoprotein (VSV-G). Mokola-, LCMV-, and VSV-G-pseudotyped vectors transduced similar populations, including striatum, thalamus, and white matter. Mokola-pseudotyped vectors were the most efficient of the three. MuLV-pseudotyped lentivirus efficiently transduced striatum and hippocampal dentate gyrus. In contrast, no transduction resulted from injection of Ebola-pseudotyped virus in the CNS. The same pattern was observed in vitro with primary cultured oligodendrocytes. LCMV, MuLV, and Ebola pseudotypes were the most stable. These results demonstrate that targeted transduction in the CNS can be achieved using specific envelope glycoproteins to pseudotype lentiviral vectors, and support the use of Mokola-pseudotyped and MuLV-pseudotyped lentiviral vectors as efficient and stable alternatives to VSV-G-pseudotyped vectors for experiments in the mouse CNS. Lentiviral vectors have proven to be promising tools for transduction of central nervous system (CNS) cells in vivo and in vitro. In this study, CNS transduction patterns of lentiviral vectors pseudotyped with envelope glycoproteins from Ebola virus, murine leukemia virus (MuLV), lymphocytic choriomeningitis virus (LCMV), or the rabies-related Mokola virus were compared to a vector pseudotyped with the vesicular stomatitis virus glycoprotein (VSV-G). Mokola-, LCMV-, and VSV-G-pseudotyped vectors transduced similar populations, including striatum, thalamus, and white matter. Mokola-pseudotyped vectors were the most efficient of the three. MuLV-pseudotyped lentivirus efficiently transduced striatum and hippocampal dentate gyrus. In contrast, no transduction resulted from injection of Ebola-pseudotyped virus in the CNS. The same pattern was observed in vitro with primary cultured oligodendrocytes. LCMV, MuLV, and Ebola pseudotypes were the most stable. These results demonstrate that targeted transduction in the CNS can be achieved using specific envelope glycoproteins to pseudotype lentiviral vectors, and support the use of Mokola-pseudotyped and MuLV-pseudotyped lentiviral vectors as efficient and stable alternatives to VSV-G-pseudotyped vectors for experiments in the mouse CNS.