SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx.
摘要：
The primate lentivirus auxiliary protein Vpx counteracts an unknown restriction factor that renders human dendritic and myeloid cells largely refractory to HIV-1 infection. Here we identify SAMHD1 as this restriction factor. SAMHD1 is a protein involved in Aicardi-Goutières syndrome, a genetic encephalopathy with symptoms mimicking congenital viral infection, that has been proposed to act as a negative regulator of the interferon response. We show that Vpx induces proteasomal degradation of SAMHD1. Silencing of SAMHD1 in non-permissive cell lines alleviates HIV-1 restriction and is associated with a significant accumulation of viral DNA in infected cells. Concurrently, overexpression of SAMHD1 in sensitive cells inhibits HIV-1 infection. The putative phosphohydrolase activity of SAMHD1 is probably required for HIV-1 restriction. Vpx-mediated relief of restriction is abolished in SAMHD1-negative cells. Finally, silencing of SAMHD1 markedly increases the susceptibility of monocytic-derived dendritic cells to infection. Our results demonstrate that SAMHD1 is an antiretroviral protein expressed in cells of the myeloid lineage that inhibits an early step of the viral life cycle.
展开
关键词：
Dendritic Cells Cell Line Hela Cells U937 Cells Myeloid Cells Humans HIV-1 HIV Infections Proteasome Endopeptidase Complex Monomeric GTP-Binding Proteins
DOI：
10.1038/nature10117
被引量：
年份：
2011
Taylor & Francis
BMJ
Nature
(全网免费下载)
Nature
Springer
查看更多
国家科技图书文献中心
(权威机构)
EBSCO
掌桥科研
万方医学
dx.doi.org
Ingenta
NCBI
Europe PMC
Europe PMC
(全网免费下载)
NCBI
Oxford Univ Press
NCBI
(全网免费下载)
Pubmed Central
(全网免费下载)
JBC
ResearchGate
ProQuest
EBSCO
EBSCO
jacionline.org
frontiersin.org
anrs.fr
(全网免费下载)
cnrs.fr
(全网免费下载)
scienceopen.com
hal.archives-ouvertes.fr
211.144.68.84:9998
(全网免费下载)
osti.gov
(全网免费下载)
hal.univ-nantes.fr
chemeurope.com
bionity.com
hal.inserm.fr
emboj.embopress.org
core.ac.uk
onacademic.com
学术范
(全网免费下载)
学术范
mendeley.com
www.socolar.com
ideas.repec.org
jimmunol.org
chemie.de
addgene.org
pubget.com
deepdyve.com
f1000.com
pubfacts.com
go.galegroup.com
bvsalud.org
genome.cshlp.org
readcube.com
hal.ird.fr
science-open.com
dumas.ccsd.cnrs.fr
mysciencework.com
cheric.org
Nature
(全网免费下载)
NCBI
(全网免费下载)
Europe PMC
(全网免费下载)
Pubmed Central
(全网免费下载)
anrs.fr
(全网免费下载)
cnrs.fr
(全网免费下载)
211.144.68.84:9998
(全网免费下载)
osti.gov
(全网免费下载)
学术范
(全网免费下载)
通过文献互助平台发起求助，成功后即可免费获取论文全文。
相似文献
参考文献
引证文献
来源期刊
引用走势
站内活动
辅助模式
引用
文献可以批量引用啦~
欢迎点我试用！
