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Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2018

Hippocampal expression of a virus-derived protein impairs memory in mice

Anne Thouard
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Cécile Malnou
Sylvie Granon

Résumé

The analysis of the biology of neurotropic viruses, notably of their interference with cellular signaling, provides a useful tool to get further insight into the role of specific pathways in the control of behavioral functions. Here, we exploited the natural property of a viral protein identified as a major effector of behavioral disorders during infection. We used the phosphoprotein (P) of Borna disease virus, which acts as a decoy substrate for protein kinase C (PKC) when expressed in neurons and disrupts synaptic plasticity. By a lentiviral-based strategy, we directed the singled-out expression of P in the dentate gyrus of the hippocampus and we examined its impact on mouse behavior. Mice expressing the P protein displayed increased anxiety and impaired long-term memory in contextual and spatial memory tasks. Interestingly, these effects were dependent on P protein phosphorylation by PKC, as expression of a mutant form of P devoid of its PKC phosphorylation sites had no effect on these behaviors. We also revealed features of behavioral impairment induced by P protein expression but that were independent of its phosphorylation by PKC. Altogether, our findings provide insight into the behavioral correlates of viral infection , as well as into the impact of virus-mediated alterations of the PKC pathway on behavioral functions. dentate gyrus | hippocampus | virus | memory | protein kinase C
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Dates et versions

hal-02400785 , version 1 (09-12-2019)

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Alexandre Betourne, Marion Szelechowski, Anne Thouard, Erika Abrial, Arnaud Jean, et al.. Hippocampal expression of a virus-derived protein impairs memory in mice. Proceedings of the National Academy of Sciences of the United States of America, 2018, 115 (7), pp.1611-1616. ⟨10.1073/pnas.1711977115⟩. ⟨hal-02400785⟩
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