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

Soheil Ghassemi (1) , Tara Asgari (1) , Hadi Mirzapour-Delavar (1) , Shayan Aliakbari (1) , Hamid Gholami Pourbadie (1) , Christophe Prehaud (2) , Monique Lafon (2) , Alireza Gholami (1) , Kayhan Azadmanesh (1) , Nima Naderi (3) , Mohammad Sayyah (1)

1 Institut Pasteur d'Iran
2 Neuro-Immunologie Virale - Viral Neuro-immunology
3 SBUMS - Shahid Beheshti University of Medical Sciences [Tehran]

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 (108 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 δRVG (deleted PBM). Furthermore, RVG and δRVG strengthened paired-pulse facilitation. Heterosynaptic long-term depression (LTD) in the DG was significantly blocked in RVG-expressing group compared to the control group. This blockade was dependent to PBM motif as rats expressing δRVG in the DG-expressed LTD comparable to the RVG group. 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 postsynaptic mechanisms to alter synaptic function. Further studies are needed to elucidate the underlying mechanisms.

Mots clés: Long term potentiation; Dentate gyrus; PDZ binding motif; Plasticity

Domaines: Immunologie

Soheil Ghassemi, Tara Asgari, Hadi Mirzapour-Delavar, Shayan Aliakbari, Hamid Gholami Pourbadie, et al.. Lentiviral Expression of Rabies Virus Glycoprotein in the Rat Hippocampus Strengthens Synaptic Plasticity. 2021. ⟨pasteur-03190429⟩