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Rabies virus glycoprotein enhances spatial memory via the PDZ binding motif

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Abstract

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 contain 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 microliter of the lentiviral vector (~108 T.U./ml) encoding RVG or ∆RVG (deleted PBM) genomes was microinjected into the hippocampal CA1. After 1 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. In the probe test, RVG-expressing rats spent more time in the target quadrant, and also reached the platform position sooner than control group (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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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran

    Soheil Ghassemi, Tara Asgari, Hamid Gholami Pourbadie & Mohammad Sayyah

  2. Institut Pasteur, Unité de Neuroimmunologie Virale, UMR 3569, CNRS, Paris, France

    Christophe Prehaud & Monique Lafon

  3. Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Nima Naderi

  4. WHO Collaborating Center for Reference and Research on Rabies, Pasteur Institute of Iran, Tehran, Iran

    Alireza Gholami

  5. Department of Virology, Pasteur Institute of Iran, Tehran, Iran

    Kayhan Azadmanesh

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  1. Soheil Ghassemi
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  2. Tara Asgari
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  3. Hamid Gholami Pourbadie
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  4. Christophe Prehaud
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  5. Monique Lafon
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  6. Nima Naderi
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Correspondence to Hamid Gholami Pourbadie or Mohammad Sayyah.

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Ghassemi, S., Asgari, T., Pourbadie, H.G. et al. Rabies virus glycoprotein enhances spatial memory via the PDZ binding motif. J. Neurovirol. 27, 434–443 (2021). https://doi.org/10.1007/s13365-021-00972-2

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  • DOI: https://doi.org/10.1007/s13365-021-00972-2

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