The SMC5/6 complex compacts and silences unintegrated HIV-1 DNA and is antagonized by Vpr.
Cell Host Microbe
; 29(5): 792-805.e6, 2021 05 12.
Article
in En
| MEDLINE
| ID: mdl-33811831
ABSTRACT
Silencing of nuclear DNA is an essential feature of innate immune responses to invading pathogens. Early in infection, unintegrated lentiviral cDNA accumulates in the nucleus yet remains poorly expressed. In HIV-1-like lentiviruses, the Vpr accessory protein enhances unintegrated viral DNA expression, suggesting Vpr antagonizes cellular restriction. We previously showed how Vpr remodels the host proteome, identifying multiple cellular targets. We now screen these using a targeted CRISPR-Cas9 library and identify SMC5-SMC6 complex localization factor 2 (SLF2) as the Vpr target responsible for silencing unintegrated HIV-1. SLF2 recruits the SMC5/6 complex to unintegrated lentiviruses, and depletion of SLF2, or the SMC5/6 complex, increases viral expression. ATAC-seq demonstrates that Vpr-mediated SLF2 depletion increases chromatin accessibility of unintegrated virus, suggesting that the SMC5/6 complex compacts viral chromatin to silence gene expression. This work implicates the SMC5/6 complex in nuclear immunosurveillance of extrachromosomal DNA and defines its targeting by Vpr as an evolutionarily conserved antagonism.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chromosomal Proteins, Non-Histone
/
HIV Infections
/
HIV-1
/
Cell Cycle Proteins
/
Vpr Gene Products, Human Immunodeficiency Virus
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Cell Host Microbe
Journal subject:
MICROBIOLOGIA
Year:
2021
Document type:
Article
Affiliation country:
Reino Unido