The host cells suppress the proliferation of pseudorabies virus by regulating the PI3K/Akt/mTOR pathway

生物 PI3K/AKT/mTOR通路 血脑屏障 蛋白激酶B 伪狂犬病 细胞生物学 病毒 信号转导 中枢神经系统 时间1 免疫学 病毒学 神经科学 基因表达 遗传学 基因
作者
Lei Xu,Qian Tao,Shouxin Zhang,Feng-qin Lee,Tong Xu,Li-shuang Deng,Zhijie Jian,Jun Zhao,Siyuan Lai,Yuancheng Zhou,Ling Zhu,Zhiwen Xu
出处
期刊:Microbiology spectrum [American Society for Microbiology]
标识
DOI:10.1128/spectrum.01351-24
摘要

ABSTRACT Pseudorabies virus (PRV), a member of the alpha-herpesviruses, can infect both the nervous and reproductive systems of pigs, causing neonatal mortality and reproductive failure in sows, which incurs substantial economic losses. Neurotropism is a common characteristic of various viruses, allowing them to cross the blood-brain barrier and access the central nervous system. However, the precise mechanisms by which PRV affects the blood-brain barrier are not well understood. To investigate the mechanism of PRV’s interaction with the blood-brain barrier and its engagement with the PI3K/Akt signaling pathway during infection, an in vitro monolayer cell model of the blood-brain barrier was established. Our research found that PRV activates Matrix metallopeptidase 2 (MMP2), which degrades Zonula occludens-1 (ZO-1) and consequently enhances the permeability of the blood-brain barrier. PRV infection elevated the transcriptional levels of tissue inhibitor of metalloproteinases 1 (TIMP1) and inhibited its degradation through the ubiquitin-proteasome pathway, leading to higher intracellular concentrations of TIMP1 protein. TIMP1 regulates apoptosis and inhibits PRV replication in mouse brain microvascular endothelial cells through the PI3K/Akt/mTOR signaling pathway. In summary, our study delineates the mechanism through which PRV compromises the blood-brain barrier and provides insights into the host’s antiviral defense mechanisms post-infection. IMPORTANCE PRV, known for its neurotropic properties, is capable of inducing severe neuronal damage. Our study discovered that following PRV infection, the expression of MMP2 was upregulated, leading to the degradation of ZO-1. Furthermore, upon PRV infection in the host, the promoter of TIMP1 is significantly activated, resulting in a significant increase in TIMP1 protein levels. This upregulation of TIMP1 inhibits the proliferation of PRV through the PI3K/Akt signaling pathway. This study elucidated the mechanism through which PRV, including the PRV XJ delgE/gI/TK strains, compromises the blood-brain barrier and identifies the antiviral response characterized by the activation of the PI3K/Akt signaling pathway within infected host cells. These findings provide potential therapeutic targets for the clinical management and treatment of PRV.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
向上的小v完成签到 ,获得积分10
1秒前
3秒前
4秒前
apple810发布了新的文献求助10
4秒前
咔哆发布了新的文献求助10
5秒前
Tink完成签到,获得积分10
5秒前
猴子魏应助zjkzh采纳,获得10
5秒前
6秒前
五木发布了新的文献求助10
7秒前
不秃头完成签到,获得积分10
8秒前
嗯哼应助一叶飘红采纳,获得20
9秒前
魏头头发布了新的文献求助10
9秒前
ethan完成签到,获得积分10
10秒前
neko完成签到,获得积分20
10秒前
A宇完成签到,获得积分10
10秒前
yiersan完成签到 ,获得积分10
11秒前
北念完成签到,获得积分10
12秒前
14秒前
Yummy完成签到 ,获得积分10
14秒前
apple810完成签到,获得积分10
15秒前
Liziqi823完成签到,获得积分10
15秒前
洋芋好完成签到,获得积分10
16秒前
小白杨完成签到 ,获得积分10
16秒前
开心听露发布了新的文献求助10
16秒前
22秒前
SciGPT应助zhanghhsnow采纳,获得30
23秒前
24秒前
hamigua完成签到 ,获得积分10
24秒前
24秒前
可爱的函函应助善良元风采纳,获得10
26秒前
Ava应助盛清让采纳,获得10
27秒前
所所应助科研通管家采纳,获得10
28秒前
28秒前
科研通AI2S应助科研通管家采纳,获得10
28秒前
28秒前
28秒前
充电宝应助科研通管家采纳,获得10
28秒前
科研通AI2S应助科研通管家采纳,获得10
28秒前
李健应助科研通管家采纳,获得10
28秒前
高分求助中
Sustainability in ’Tides Chemistry 2000
Studien zur Ideengeschichte der Gesetzgebung 1000
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
Threaded Harmony: A Sustainable Approach to Fashion 810
Handbook of the Mammals of the World – Volume 3: Primates 805
Ethnicities: Media, Health, and Coping 800
Gerard de Lairesse : an artist between stage and studio 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3074349
求助须知:如何正确求助?哪些是违规求助? 2727785
关于积分的说明 7500402
捐赠科研通 2375884
什么是DOI,文献DOI怎么找? 1259599
科研通“疑难数据库(出版商)”最低求助积分说明 610725
版权声明 597081