Nuclear pore blockade reveals that HIV-1 completes reverse transcription and uncoating in the nucleus

衣壳 核运输 核孔 细胞核 细胞生物学 生物 抄写(语言学) 核心 细胞质 转录因子 核定位序列 逆转录酶 病毒复制 核糖核酸 病毒学 病毒 基因 遗传学 哲学 语言学
作者
Adarsh Dharan,Niklas Bachmann,Sarah Talley,Virginia Zwikelmaier,Edward M. Campbell
出处
期刊:Nature microbiology 卷期号:5 (9): 1088-1095 被引量:152
标识
DOI:10.1038/s41564-020-0735-8
摘要

Retroviral infection involves the reverse transcription of the viral RNA genome into DNA, which is subsequently integrated into the host cell genome. Human immunodeficiency virus type 1 (HIV-1) and other lentiviruses mediate the infection of non-dividing cells through the ability of the capsid protein1 to engage the cellular nuclear import pathways of the target cell and mediate their nuclear translocation through components of the nuclear pore complex2–4. Although recent studies have observed the presence of the capsid protein in the nucleus during infection5–8, reverse transcription and disassembly of the viral core have conventionally been considered to be cytoplasmic events. Here, we use an inducible nuclear pore complex blockade to monitor the kinetics of HIV-1 nuclear import and define the biochemical staging of these steps of infection. Surprisingly, we observe that nuclear import occurs with relatively rapid kinetics (<5 h) and precedes the completion of reverse transcription in target cells, demonstrating that reverse transcription is completed in the nucleus. We also observe that HIV-1 remains susceptible to the capsid-destabilizing compound PF74 following nuclear import, revealing that uncoating is completed in the nucleus. Additionally, we observe that certain capsid mutants are insensitive to a Nup62-mediated nuclear pore complex blockade in cells that potently block infection by wild-type capsid, demonstrating that HIV-1 can use distinct nuclear import pathways during infection. These studies collectively define the spatio-temporal staging of critical steps of HIV-1 infection and provide an experimental system to separate and thereby define the cytoplasmic and nuclear stages of infection by other viruses. HIV-1 reverse transcription is found to be completed in the nucleus of the cell using an HIV-1 nuclear import kinetic assay that takes advantage of a nuclear import blockade method to monitor the kinetics of HIV-1 entry and infection.
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
流年亦梦完成签到 ,获得积分10
1秒前
蟒玉朝天完成签到 ,获得积分10
1秒前
Owen应助跋扈采纳,获得10
2秒前
奥斯卡奥卡凡关注了科研通微信公众号
3秒前
3秒前
大个应助今天也爱看文献采纳,获得30
3秒前
材料打工人完成签到,获得积分10
4秒前
Cccc小懒发布了新的文献求助50
5秒前
6秒前
6秒前
7秒前
面包完成签到,获得积分10
7秒前
郝出站完成签到,获得积分10
7秒前
8秒前
务实的小虾米完成签到,获得积分10
8秒前
wzj完成签到,获得积分10
10秒前
13秒前
13秒前
斯文明杰发布了新的文献求助10
13秒前
暴躁的马里奥完成签到,获得积分10
13秒前
叙温雨发布了新的文献求助10
14秒前
今天也爱看文献完成签到,获得积分10
14秒前
YiWei完成签到 ,获得积分10
14秒前
Z_yiming关注了科研通微信公众号
14秒前
落日游云发布了新的文献求助10
15秒前
17秒前
丘比特应助美丽的宝马采纳,获得10
17秒前
Frida完成签到,获得积分10
18秒前
19秒前
wanci应助Aic采纳,获得10
19秒前
19秒前
19秒前
跋扈发布了新的文献求助10
20秒前
璐洋发布了新的文献求助10
22秒前
学术小白完成签到,获得积分10
22秒前
小沐发布了新的文献求助10
23秒前
25秒前
璐洋完成签到,获得积分10
28秒前
28秒前
高分求助中
Evolution 10000
Sustainability in Tides Chemistry 2800
юрские динозавры восточного забайкалья 800
Diagnostic immunohistochemistry : theranostic and genomic applications 6th Edition 500
Chen Hansheng: China’s Last Romantic Revolutionary 500
China's Relations With Japan 1945-83: The Role of Liao Chengzhi 400
Classics in Total Synthesis IV 400
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 3149289
求助须知:如何正确求助?哪些是违规求助? 2800391
关于积分的说明 7839862
捐赠科研通 2457980
什么是DOI,文献DOI怎么找? 1308158
科研通“疑难数据库(出版商)”最低求助积分说明 628456
版权声明 601706