Memory Impairment Induced by Borna Disease Virus 1 Infection is Associated with Reduced H3K9 Acetylation

Abstract

Background/Aims: Borna disease virus 1 (BoDV-1) infection induces cognitive impairment in rodents. Emerging evidence has demonstrated that Chromatin remodeling through histone acetylation can regulate cognitive function. In the present study, we investigated the epigenetic regulation of chromatin that underlies BoDV-1-induced cognitive changes in the hippocampus. Methods: Immunofluorescence assay was applied to detect BoDV-1 infection in hippocampal neurons and Sprague-Dawley rats models. The histone acetylation levels both in vivo and vitro were assessed by western blots. The acetylation-regulated genes were identified by ChIP-seq and verified by RT-qPCR. Cognitive functions were evaluated with Morris Water Maze test. In addition, Golgi staining, and electrophysiology were used to study changes in synaptic structure and function. Results: BoDV-1 infection of hippocampal neurons significantly decreased H3K9 histone acetylation level and inhibited transcription of several synaptic genes, including postsynaptic density 95 (PSD95) and brain-derived neurotrophic factor (BDNF). Furthermore, BoDV-1 infection of Sprague Dawley rats disrupted synaptic plasticity and caused spatial memory impairment. These rats also exhibited dysregulated hippocampal H3K9 acetylation and decreased PSD95 and BDNF protein expression. Treatment with the HDAC inhibitor, suberanilohydroxamic acid (SAHA), attenuated the negative effects of BoDV-1. Conclusion: Our results demonstrate that regulation of H3K9 histone acetylation may play an important role in BoDV-1-induced memory impairment, whereas SAHA may confer protection against BoDV-1-induced cognitive impairments. This study finds important

Borna disease virus docks on neuronal DNA double-strand breaks to replicate and dampens neuronal activity

“…In these non-dividing cells that establish lifelong specialized networks, while remaining able of a high degree of adaptability called plasticity, epigenetic mechanisms are critical regulators. As a result, epigenetic processes of the host cell are also often hijacked by persistent viruses (Bonnaud et al, 2016;Lange et al, 2020;Tarakhovsky and Prinjha, 2018) and BoDV-1 is no exception: our group and others identified BoDV-1 P-mediated ll OPEN ACCESS iScience 25, 103621, January 21, 2022 iScience Article interference with acetylation of Histone H2B and H3 (Bonnaud et al, 2015;Jie et al, 2018). Because DSB can be induced by both P and N proteins, and early DSB accumulation in neurons increases Histone H3 lysine 9 dimethylation (Suberbielle et al, 2015), which corresponds to inhibitory signals of gene expression, it is tempting to speculate that DSB and their signaling may play an upstream role in the further deacetylation of histones.…”

BoDV‐1 infection induces neuroinflammation by activating the TLR4/MyD88/IRF5 signaling pathway, leading to learning and memory impairment in rats

“…15 However, persistently infected rats will have severe hippocampal damage, and slight learning and behavioral impairments can be observed. [13][14][15][16] Our previous studies have shown that BoDV-1 infection can impair the cognitive function of rats, 17,18 but the relevant mechanisms and pathways are still unclear.…”

miR-505 inhibits replication of Borna disease virus 1 via inhibition of HMGB1-mediated autophagy

“…BoDV-1 strain Hu-H1 was isolated from a patient with bipolar disorder in 1994 [46][47][48]. Cell-free BoDV-1 stock was prepared as described previously [14,49] and used to infect primary cortical neurons.…”

“…BoDV-1 replicates in the cell nucleus, a characteristic unique to the order Mononegavirales [4], and persistently infects a wide range of vertebrate species with a broad global geographical distribution [5][6][7][8][9][10]. As a highly neurotropic virus, infection by BoDV-1 leads to a spectrum of neurological diseases ranging from immune-mediated acute fatal encephalitis to non-inflammatory behavioural changes [11][12][13][14][15][16][17][18]. Although the relationship between BoDV-1 and human psychiatric disorders has been controversial for many years [19,20], recently a series of solid evidence suggests that humans could be a target for BDV infection.…”