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Virology Journal
Published in: Virology Journal 1/2019

Open Access 01-12-2019 | Human Immunodeficiency Virus | Research

Histone deacetylase 1 interacts with HIV-1 Integrase and modulates viral replication

Authors: Fadila Larguet, Clément Caté, Benoit Barbeau, Eric Rassart, Elsy Edouard

Published in: Virology Journal | Issue 1/2019

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Abstract

Background

HIV-1 hijacks the cellular machinery for its own replication through protein-protein interactions between viral and host cell factors. One strategy against HIV-1 infection is thus to target these key protein complexes. As the integration of reverse transcribed viral cDNA into a host cell chromosome is an essential step in the HIV-1 life cycle, catalyzed by the viral integrase and other important host factors, we aimed at identifying new integrase binding partners through a novel approach.

Methods

A LTR-derived biotinylated DNA fragment complexed with the integrase on magnetic beads was incubated with extracts from integrase-expressing 293 T cells. Liquid chromatography-mass spectrometry/mass spectrometry and co-immunoprecipitation/pull-down experiments were used for the identification of binding partners. Transfections of histone deacetylase 1 (HDAC1) expression vectors and/or specific siRNA were conducted in HeLa-CD4 and 293 T cells followed by infection with fully infectious NL4–3 and luciferase-expressing pseudotyped viruses or by proviral DNA transfection. Fully infectious and pseudotyped viruses produced from HDAC1-silenced 293 T cells were tested for their infectivity toward HeLa-CD4 cells, T cell lines and primary CD4+ T cells. Late RT species and integrated viral DNA were quantified by qPCR and infectivity was measured by luciferase activity and p24 ELISA assay. Results were analyzed by the Student’s t-test.

Results

Using our integrase-LTR bait approach, we successfully identified new potential integrase-binding partners, including HDAC1. We further confirmed that HDAC1 interacted with the HIV-1 integrase in co-immunoprecipitation and pull-down experiments. HDAC1 knockdown in infected HeLa cells was shown to interfere with an early preintegration step of the HIV-1 replication cycle, which possibly involves reverse transcription. We also observed that, while HDAC1 overexpression inhibited HIV-1 expression after integration, HDAC1 knockdown had no effect on this step. In virus producer cells, HDAC1 knockdown had a limited impact on virus infectivity in either cell lines or primary CD4+ T cells.

Conclusions

Our results show that HDAC1 interacts with the HIV-1 integrase and affects virus replication before and after integration. Overall, HDAC1 appears to facilitate HIV-1 replication with a major effect on a preintegration step, which likely occurs at the reverse transcription step.
Appendix
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Metadata
Title
Histone deacetylase 1 interacts with HIV-1 Integrase and modulates viral replication
Authors
Fadila Larguet
Clément Caté
Benoit Barbeau
Eric Rassart
Elsy Edouard
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2019
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-019-1249-y

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