Format

Send to

Choose Destination
AIDS. 2019 Oct 1;33(12):1819-1830. doi: 10.1097/QAD.0000000000002288.

IL-27 posttranslationally regulates Y-box binding protein-1 to inhibit HIV-1 replication in human CD4+ T cells.

Author information

1
Laboratory of Human Retrovirology and Immunoinformatics.
2
AIDS Monitoring Laboratory.
3
Protein Characterization Laboratory.
4
Immmunological Monitoring Laboratory, Applied and Developmental Research Directorate, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.

Abstract

OBJECTIVES:

IL-27 is known as an antiviral cytokine that inhibits HIV, hepatitis C virus, and other viruses. We have previously demonstrated that, IL-27 posttreatment after HIV-infection inhibits viral replication in primary CD4 T cells.

DESIGN:

Here, we evaluated the anti-HIV effect of IL-27 pretreatment in CD4 T cells from healthy donors prior to HIV infection with HIVNL4.3 or vesicular stomatitis virus G glycoprotein (VSV-G)-pseudotyped HIV-luciferase virus (HIV-LUC-V).

METHODS:

IL-27-treated CD4 T cells were infected with HIVNL4.3 or HIV-LUC-V and assessed the anti-HIV effect. HIV infection was monitored by p24 antigen ELISA or luciferase assay. HIV fusion/entry and uncoating were determined by BlaM-Vpr assay and HIV fate of capsid and/or HIV Entry/Uncoating assay based on core-packaged RNA availability and Translation assay, respectively. HIV proviral copy number was determined by real-time PCR. Gene expression profile from IL-27-pretreated CD4 T cells was determined using Genechip array. Posttranslational modification of global proteins from IL-27-pretreated CD4 T cells was determined by a combination of 2-dimensional difference-in-gel-electrophoresis (2D-DIG), western-blot and protein mass spectrometry.

RESULTS:

IL-27 pretreatment inhibited HIVNL4.3 and HIV-LUC-V infection in CD4 T cells. HIV copy assay demonstrated that IL-27-treatment suppressed an early step of reverse transcription during HIV infection. A combination of 2D-DIG-electrophoresis and western blot assays demonstrated that IL-27-treatment induces a change in posttranslational modification of Y box binding protein-1 (YB-1). Overexpression of domain negative YB-1 mutants illustrated that a residue Lysine at 118 plays a key role in supporting HIV infection in CD4 T cells.

CONCLUSION:

IL-27-pretreatment inhibits HIV-1 infection by suppressing an HIV-reverse transcription product formation/uncoating step by suppressing the acetylation of YB-1 in primary CD4 T cells.

PMID:
31274540
PMCID:
PMC6731144
[Available on 2020-10-01]
DOI:
10.1097/QAD.0000000000002288

Supplemental Content

Full text links

Icon for Wolters Kluwer Icon for PubMed Central
Loading ...
Support Center