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HIV-1 Vpr antagonizes innate immune activation by targeting karyopherin-mediated NF-κB/IRF3 nuclear transport.
- Source :
-
eLife . 12/24/2020, p1-29. 29p. - Publication Year :
- 2020
-
Abstract
- HIV-1 must replicate in cells that are equipped to defend themselves from infection through intracellular innate immune systems. HIV-1 evades innate immune sensing through encapsidated DNA synthesis and encodes accessory genes that antagonize specific antiviral effectors. Here, we show that both particle associated, and expressed HIV-1 Vpr, antagonize the stimulatory effect of a variety of pathogen associated molecular patterns by inhibiting IRF3 and NF-κB nuclear transport. Phosphorylation of IRF3 at S396, but not S386, was also inhibited. We propose that, rather than promoting HIV-1 nuclear import, Vpr interacts with karyopherins to disturb their import of IRF3 and NF-κB to promote replication in macrophages. Concordantly, we demonstrate Vpr-dependent rescue of HIV-1 replication in human macrophages from inhibition by cGAMP, the product of activated cGAS. We propose a model that unifies Vpr manipulation of nuclear import and inhibition of innate immune activation to promote HIV-1 replication and transmission. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HIV
*DNA synthesis
*KARYOPHERINS
*IMMUNE system
Subjects
Details
- Language :
- English
- ISSN :
- 2050084X
- Database :
- Academic Search Index
- Journal :
- eLife
- Publication Type :
- Academic Journal
- Accession number :
- 152077737
- Full Text :
- https://doi.org/10.7554/eLife.60821