"Borna disease virus 1 impairs DNA double-strand break repair through the ATR/Chk1 signalling pathway, resulting in learning and memory impairment in rats"

作者全名："Shen, Xia; Xu, Xiaoyan; Guo, Yujie; Yang, Hongli; He, Juan; Xie, Peng"

作者地址："[Shen, Xia; Yang, Hongli; Xie, Peng] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing, Peoples R China; [Shen, Xia; Xu, Xiaoyan; Guo, Yujie; Yang, Hongli; Xie, Peng] Chongqing Med Univ, Affiliated Hosp 1, NHC Key Lab Diag & Treatment Brain Funct Dis, Chongqing, Peoples R China; [Xu, Xiaoyan; He, Juan] Chongqing Med Univ, Dept Pathol, Coll Basic Med, Chongqing, Peoples R China; [Guo, Yujie] Chongqing Med Univ, Yongchuan Hosp, Dept Neurol, Chongqing, Peoples R China"

通信作者："Xie, P (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing, Peoples R China.; Xie, P (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, NHC Key Lab Diag & Treatment Brain Funct Dis, Chongqing, Peoples R China."

来源：JOURNAL OF GENERAL VIROLOGY

ESI学科分类：MICROBIOLOGY

WOS号：WOS:001025100000001

JCR分区：Q2

影响因子：3.8

年份：2022

卷号：103

期号：12

开始页：　

结束页：　

文献类型：Article

关键词：Borna disease virus 1; cognitive dysfunction; DNA repair; DNA double-strand breaks

摘要："Borna disease virus 1 (BoDV-1) is a highly neurotropic RNA virus that can establish persistent infection in the central nervous system and cause cognitive dysfunction in neonatally infected rats. However, the mechanisms that lead to this cognitive impairment remain unclear. DNA double-strand breaks (DSBs) and their repair are associated with brain development and cognition. If DNA repair in the brain is reduced or delayed and DNA damage accumulates, abnormal cognitive function may result. We generated a rat model of BoDV-1 infection during the neonatal period and assessed behavioural changes using the open field test and Morris water maze. The levels of DSBs were determined by immunofluorescence and comet assays. Western blotting assessed proteins associated with DNA repair pathways. The results showed that BoDV-1 downregulated the ATR/Chk1 signalling pathway in the brain, impairing DNA damage repair and increasing the number of DSBs, which ultimately leads to cognitive dysfunction. Our findings suggest a molecular mechanism by which BoDV-1 interferes with DNA damage repair to cause learning and memory impairment. This provides a theoretical basis for elucidating BoDV-1- induced neurodevelopmental impairment."

基金机构：National Key R&D Program of China [2017YFA0505700]; Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences [2019PT320002]; Natural Science Foundation Project of China [81820108015]; Chongqing Technology Innovation and Application Development Special Project [cstc2021jscx-msxm0035]; Chongqing Postdoctoral Science Fund Project [cstc2021jcyj-bshX0111]; China Postdoctoral Science Foundation [2021MD703922]

基金资助正文："This study was supported by the National Key R&D Program of China (grant no. 2017YFA0505700), the Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences (grant no. 2019PT320002), the Natural Science Foundation Project of China (grant no. 81820108015), Chongqing Technology Innovation and Application Development Special Project (grant no. cstc2021jscx-msxm0035), Chongqing Postdoctoral Science Fund Project (grant no. cstc2021jcyj-bshX0111) and China Postdoctoral Science Foundation(grant no. 2021MD703922)."