亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

Inhibition of Infectious HIV-1 Production by Rerouting the Cellular Furin Inhibitor Serpin B8

蛋白酵素 毛皮 生物 舍宾 前蛋白转化酶 传染性 病毒学 细胞生物学 病毒 生物化学 基因 低密度脂蛋白受体 胆固醇 脂蛋白
作者
Moritz Petersen,Rishikesh Lotke,Kristina Hopfensperger,Sabina Victoria,Isabell Haußmann,Timo Burster,Hanna‐Mari Baldauf,Daniel Sauter
出处
期刊:Journal of Virology [American Society for Microbiology]
卷期号:97 (6)
标识
DOI:10.1128/jvi.00294-23
摘要

Serpins are a superfamily of proteins that regulate a variety of physiological processes by irreversibly inhibiting the enzymatic activity of different serine proteases. For example, Serpin Family B Member 8 (Serpin B8, also known as PI8 and CAP2) binds to and inhibits the proprotein convertase furin. Like many other viral pathogens, human immunodeficiency virus type 1 (HIV-1) exploits furin for the proteolytic activation of its envelope glycoprotein (Env). Since the furin inhibitor Serpin B8 is expressed in primary target cells of HIV-1 and induced under inflammatory conditions, we hypothesized that it might interfere with HIV-1 Env maturation and decrease infectivity of newly produced virions. Indeed, recombinant Serpin B8 reduced furin-mediated cleavage of an HIV-1 Env reporter substrate in vitro. However, Serpin B8 did not affect Env maturation or reduce HIV-1 particle infectivity when expressed in HIV-1-producing cells. Immunofluorescence imaging, dimerization assays and in silico sequence analyses revealed that Serpin B8 failed to inhibit intracellular furin since both proteins localized to different subcellular compartments. We therefore aimed at rendering Serpin B8 active against HIV-1 by relocalizing it to furin-containing secretory compartments. Indeed, the addition of a heterologous signal peptide conferred potent anti-HIV-1 activity to Serpin B8 and significantly decreased infectivity of newly produced viral particles. Thus, our findings demonstrate that subcellular relocalization of a cellular protease inhibitor can result in efficient inhibition of infectious HIV-1 production. IMPORTANCE Many cellular proteases serve as dependency factors during viral infection and are hijacked by viruses for the maturation of their own (glyco)proteins. Consequently, inhibition of these cellular proteases may represent a means to inhibit the spread of viral infection. For example, several studies have investigated the serine protease furin as a potential therapeutic target since this protease cleaves and activates several viral envelope proteins, including HIV-1 Env. Besides the development of small molecule inhibitors, cell-intrinsic protease inhibitors may also be exploited to advance current antiviral treatment approaches. Here, we show that Serpin B8, an endogenous furin inhibitor, can inhibit HIV-1 Env maturation and efficiently reduce infectious HIV-1 production when rerouted to the secretory pathway. The results of our study not only provide important insights into the biology of Serpins, but also show how protein engineering of an endogenous furin inhibitor can render it active against HIV-1.
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
FashionBoy应助zhao123123采纳,获得30
2秒前
1分钟前
zhao123123发布了新的文献求助30
1分钟前
明理的夜蓉完成签到 ,获得积分10
1分钟前
1分钟前
zhao123123完成签到,获得积分10
1分钟前
白云朵儿发布了新的文献求助10
1分钟前
2分钟前
2分钟前
YUNUN发布了新的文献求助10
2分钟前
2分钟前
orixero应助海燕采纳,获得30
3分钟前
3分钟前
海燕发布了新的文献求助30
3分钟前
NexusExplorer应助菜菜采纳,获得10
3分钟前
4分钟前
菜菜发布了新的文献求助10
4分钟前
YUNUN完成签到,获得积分20
4分钟前
白云朵儿发布了新的文献求助10
4分钟前
南湘完成签到 ,获得积分10
5分钟前
6分钟前
晓晓晓完成签到,获得积分20
6分钟前
晓晓晓发布了新的文献求助10
6分钟前
6分钟前
Rin发布了新的文献求助10
7分钟前
7分钟前
7分钟前
Rigel完成签到,获得积分10
8分钟前
Rigel发布了新的文献求助10
8分钟前
Flexy发布了新的文献求助10
8分钟前
Flexy发布了新的文献求助10
8分钟前
科研通AI2S应助Flexy采纳,获得10
9分钟前
欢喜的慕青完成签到 ,获得积分10
9分钟前
昵称完成签到 ,获得积分10
9分钟前
江湖小妖完成签到 ,获得积分10
11分钟前
11分钟前
俏皮诺言完成签到,获得积分10
11分钟前
messi发布了新的文献求助30
11分钟前
星辰大海应助海燕采纳,获得30
12分钟前
Ji完成签到 ,获得积分10
12分钟前
高分求助中
Un calendrier babylonien des travaux, des signes et des mois: Séries iqqur îpuš 1036
Sustainable Land Management: Strategies to Cope with the Marginalisation of Agriculture 1000
Corrosion and Oxygen Control 600
Heterocyclic Stilbene and Bibenzyl Derivatives in Liverworts: Distribution, Structures, Total Synthesis and Biological Activity 500
重庆市新能源汽车产业大数据招商指南(两链两图两池两库两平台两清单两报告) 400
Division and square root. Digit-recurrence algorithms and implementations 400
行動データの計算論モデリング 強化学習モデルを例として 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 有机化学 工程类 生物化学 纳米技术 物理 内科学 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 电极 光电子学 量子力学
热门帖子
关注 科研通微信公众号,转发送积分 2545602
求助须知:如何正确求助?哪些是违规求助? 2175642
关于积分的说明 5600185
捐赠科研通 1896371
什么是DOI,文献DOI怎么找? 946248
版权声明 565371
科研通“疑难数据库(出版商)”最低求助积分说明 503557