IFI44 suppresses HIV-1 LTR promoter activity and facilitates its latency

Virology
Derek PowerJian Zhu

Abstract

IFI44 is an interferon-alfa inducible protein, and is associated with infection of several viruses. However, IFI44 elicits minimal antiviral effects on these viruses, and its exact role is still unknown. Here we show that IFI44 inhibits HIV-1 replication in vitro. Through depletion of endogenous IFI44 or overexpression of IFI44 we confirm that IFI44 suppresses HIV-1 LTR promoter activity and affects viral transcription. Furthermore, we find that IFI44 localizes to nuclei and binds to the HIV-1 LTR promoter in HIV-1 infected cells. Removing suppression of HIV-1 transcription benefits reactivation of HIV-1 proviruses for purging latent reservoirs. We demonstrate that depletion of endogenous IFI44 in J-LAT cells induces reactivation of latent HIV-1. Based on these results, we propose a model in which IFI44 is recruited to the HIV-1 LTR, which may suppress viral transcription and prevent reactivation of latent HIV-1. Our study suggests a previously unrecognized anti-HIV phenomenon for interferon-stimulated proteins.

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Citations

Dec 17, 2015·Expert Opinion on Investigational Drugs·David M AsmuthRichard B Pollard
Jan 13, 2018·Microbiology and Molecular Biology Reviews : MMBR·Jean-François GélinasStephen C Hyde
Dec 23, 2017·Asian-Australasian Journal of Animal Sciences·Joon Ki HongDeuk Hwan Lee
Oct 9, 2018·PloS One·Poonam RathDavid S Schneider
Nov 17, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jean-Pierre LevraudPierre Boudinot
Oct 31, 2018·Frontiers in Immunology·Karima KessalFrançoise Brignole-Baudouin
Apr 2, 2020·Frontiers in Cellular and Infection Microbiology·Shuang LuWei Hou
Oct 31, 2020·Frontiers in Immunology·Unni GrimholtArvind Y M Sundaram
May 11, 2021·Frontiers in Cell and Developmental Biology·Mounira K Chelbi-Alix, Pierre Thibault
Sep 2, 2021·Cell Reports·Sneha RatnapriyaAlon Herschhorn

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