HUSH, a Link Between Intrinsic Immunity and HIV Latency

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2019 Feb 28

PMID 30809215

Citations 15

Authors

Ghina Chougui

Florence Margottin-Goguet

Affiliations

Soon will be listed here.

Abstract

A prominent obstacle to HIV eradication in seropositive individuals is the viral persistence in latent reservoir cells, which constitute an HIV sanctuary out of reach of highly active antiretroviral therapies. Thus, the study of molecular mechanisms governing latency is a very active field that aims at providing solutions to face the reservoirs issue. Since the past 15 years, another major field in HIV biology focused on the discovery and study of restriction factors that shape intrinsic immunity, while engaging in a molecular battle against HIV. Some of these restrictions factors act at early stages of the virus life cycle, alike SAMHD1 antagonized by the viral protein Vpx, while others are late actors. Until recently, no such factor was identified in the nucleus and found active at the level of provirus expression, a crucial step where latency may take place. Today, two studies highlight Human Silencing Hub (HUSH) as a potential restriction factor that controls viral expression and is antagonized by Vpx. This Review discusses HUSH restriction in the light of the actual knowledge of intrinsic immunity and HIV latency.

Citing Articles

Regulation of viral replication by host restriction factors.

Lin Y, Zhu Y, Jing L, Lei X, Xie Z Front Immunol. 2025; 16:1484119.

PMID: 39917304 PMC: 11798991. DOI: 10.3389/fimmu.2025.1484119.

The HUSH epigenetic repressor complex silences PML nuclear body-associated HSV-1 quiescent genomes.

Roubille S, Escure T, Juillard F, Corpet A, Neplaz R, Binda O Proc Natl Acad Sci U S A. 2024; 121(49):e2412258121.

PMID: 39589886 PMC: 11626126. DOI: 10.1073/pnas.2412258121.

Keep quiet: the HUSH complex in transcriptional silencing and disease.

Muller I, Helin K Nat Struct Mol Biol. 2024; 31(1):11-22.

PMID: 38216658 DOI: 10.1038/s41594-023-01173-7.

The innate immune factor RPRD2/REAF and its role in the Lv2 restriction of HIV.

Jackson-Jones K, McKnight A, Sloan R mBio. 2023; 14(6):e0257221.

PMID: 37882563 PMC: 10746242. DOI: 10.1128/mbio.02572-21.

The KT Jeang Retrovirology prize 2022: Florence Margottin-Goguet.

Retrovirology. 2022; 19(1):20.

PMID: 36068604 PMC: 9446835. DOI: 10.1186/s12977-022-00606-3.

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