The Lentiviral Vector Pseudotyped by Modified Rabies Glycoprotein Does Not Cause Reactive Gliosis and Neurodegeneration in Rat Hippocampus

Background: A human immunodeficiency virus type 1 (HIV-1)-based lentiviral vector (LV) pseudotyped by a variant of rabies envelope glycoprotein, FUG-B2, has previously been prepared and used in transfection of hippocampal CA1 ("Cornu Ammonis" area 1) neurons. This study aimed to verify reactive gliosis and neuronal damage after injection of the vector into the rat hippocampus. Methods: HEK 293T cells were transfected with transfer (fck-Jaws-GFP-ER2), envelope (FUG-B2), and packaging (pMDLg/pRRE, pRSV-Rev) plasmids, and the vector was injected into CA1 of the rat hippocampus. After one week, transduction efficiency, and the number of neuronal and astroglial cells were determined in CA1 and CA3 by double staining of the brain slices. Results: Hippocampal cells were successfully transfected as 92.7% of CA1 and 95.8% of CA3 neuronal cells expressed GFP. The frequency of neuronal and astroglial cells in CA1 and CA3 of the vector-injected rats remained unchanged compared to those in the control and the saline-injected rats. Furthermore, no morphological change was found in hippocampal astrocytes and neuronal cells. Conclusion: The HIV-1-based LV pseudotyped by FUG-B2 is safe and does not cause neuroinflammation and neuronal loss once directly delivered into the rat hippocampus.