Transduction efficacy and retrograde movement of a lentiviral vector pseudotyped by modified rabies glycoprotein throughout the trisynaptic circuit of the rat hippocampus

Farzaneh, Mostafa; Sayyah, Mohammad; Eshraghi, Hamid Reza; Panahi, Negar; Delavar, Hadi Mirzapour; Pourbadie, Hamid Gholami

doi:10.1002/jgm.3046

Cited by 7 publications

(9 citation statements)

References 12 publications

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“…We have recently reported that the HIV-1-based LV pseudotyped by FUG-B2 is able to transduce more than 90% of hippocampal neurons one week after intra-hippocampal injection [ 4 ] . Meanwhile, the process of gliosis, considering astrogliosis as the final component of this process, takes place over several days [ 13 ] .…”

Section: Discussionmentioning

confidence: 99%

“…Two microliters of the LV stock (2 × 10 8 TU/ml) was infused twice (with a 24-h interval between the injections) into the CA1 region (n = 3) of the right dorsal hippocampus according to the previously described method [ 4 ] . In the control group (n = 3), rats received physiologic saline (NaCl 0.9%, pH 7.4) instead of the LV.…”

Section: Methodsmentioning

confidence: 99%

“…The brain of rats was dissected out seven days after infusion of the LV and saline, or the induction of TBI. Preparing the brain coronal sections and immunohistochemistry were performed according to the previously described method [ 4 ] . Eight-μm-thick coronal sections were made using a tissue slicer (Leica, Germany), processed and incubated with anti-NeuN antibody, 1:700.…”

Section: Methodsmentioning

confidence: 99%

“…Delivery of this LV into the peripheral and CNS is accompanied by the successful transfer of the gene into the neurons distal to the injection site by retrograde axonal transport [2,3] . We have recently generated a HIV-1-based LV pseudotyped by a variant of rabies glycoprotein, fusion glycoprotein variant B2 (FUG-B2), with an acceptable titer [ 4 ] . The LV showed high gene transfer efficiency in the Schaffer collateral pathway in both postsynaptic neurons existing at the delivery sites CA1 and presynaptic neurons in CA3, by retrograde axonal transport [4] .…”

Section: Introductionmentioning

confidence: 99%

“…The LV showed high gene transfer efficiency in the Schaffer collateral pathway in both postsynaptic neurons existing at the delivery sites CA1 and presynaptic neurons in CA3, by retrograde axonal transport [4] . Moreover, the transgene was highly expressed in both CA1 and CA3 pyramidal neurons for at least two months after vector injection [ 4 ] .…”

Section: Introductionmentioning

confidence: 99%

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

Farzaneh

Sayyah

Eshraghi

et al. 2019

ibj

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Farzaneh

Sayyah

Eshraghi

et al. 2019

ibj

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Lentiviral Expression of Rabies Virus Glycoprotein in the Rat Hippocampus Strengthens Synaptic Plasticity

et al. 2021

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Rabies virus (RABV) is a neurotropic virus exclusively infecting neurons in the central nervous system. RABV encodes five proteins. Among them, the viral glycoprotein (RVG) plays a key role in viral entry into neurons and rabies pathogenesis. It was shown that the nature of the C-terminus of the RABV G protein, which possesses a PDZ binding motif (PBM) modulates the virulence of the RABV strain. The neuronal protein partners recruited by this PBM may alter host cell function. This study was conducted to investigate the effect of RVG on synaptic function in the hippocampal dentate gyrus (DG) of rat.Two μl (10 8 T.U. /ml) of the lentiviral vector containing RVG gene was injected into the DG of rat hippocampus. After 2 weeks, the rat's brain was cross-sectioned and RVG-expressing cells were detected by fluorescent microscopy. Hippocampal synaptic activity of the infected rats was then examined by recording the local field potentials from DG after stimulation of the perforant pathway. Short term synaptic plasticity was also assessed by double pulse stimulation.Expression of RVG in DG increased long term potentiation population spikes (LTP-PS), whereas no facilitation of LTP-PS was found in neurons expressing ∆RVG (deleted PBM). Furthermore, RVG and ∆RVG strengthened paired pulse facilitation.Our data demonstrate that RVG expression facilitates both short and long term synaptic plasticity in the DG indicating that it may involve both pre-and post-synaptic mechanisms to alter synaptic function. Further studies are needed to elucidate the underlying mechanisms.

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Rabies virus glycoprotein enhances spatial memory via the PDZ binding motif

et al. 2021

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Rabies is a life-threatening viral infection of the brain. Rabies virus (RABV) merely infects excitable cells including neurons provoking drastic behaviors including negative emotional memories. RABV glycoprotein (RVG) plays a critical role in RABV pathogenesis. RVG interacts with various cytoplasmic PDZ (PSD-95/Dlg/ZO-1) containing proteins through its PDZ binding motif (PBM). PTZ domains have crucial role in formation and function of signal transduction.Hippocampus is one of the cerebral regions that contains high load of viral antigens. We examined impact of RVG expression in the dorsal hippocampus on aversive as well as spatial learning and memory performance in rats.Two μl of the lentiviral vector (~10 8 T.U. /ml) encoding RVG or ∆RVG (deleted PBM) genomes was microinjected into the hippocampal CA1. After one week, rat's brain was cross-sectioned and RVG/∆RVG-expressing neuronal cells were confirmed by fluorescent microscopy. Passive avoidance and spatial learning and memory were assessed in rats by Shuttle box and Morris water maze (MWM).In the shuttle box, both RVG and ∆RVG decreased the time spent in the dark compartment compared to control (p<0.05). In MWM, RVG and ∆RVG did not affect the acquisition of spatial task. RVG-expressing rats reached the platform position in the probe test sooner than control and ∆RVG groups (p<0.05). Rats expressing ∆RVG significantly swam farther from the hidden platform than RVG group (p<0.05).Our data indicate RVG expression in the hippocampus strengthens aversive and spatial learning and memory performance. The boosting effect on spatial but not avoidance memory is mediated through PBM.

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Transduction efficacy and retrograde movement of a lentiviral vector pseudotyped by modified rabies glycoprotein throughout the trisynaptic circuit of the rat hippocampus

Cited by 7 publications

References 12 publications

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

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

Lentiviral Expression of Rabies Virus Glycoprotein in the Rat Hippocampus Strengthens Synaptic Plasticity

Rabies virus glycoprotein enhances spatial memory via the PDZ binding motif

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