» Articles » PMID: 35769258

DEAD-ly Affairs: The Roles of DEAD-Box Proteins on HIV-1 Viral RNA Metabolism

Overview
Specialty Cell Biology
Date 2022 Jun 30
PMID 35769258
Authors
Affiliations
Soon will be listed here.
Abstract

In order to ensure viral gene expression, Human Immunodeficiency virus type-1 (HIV-1) recruits numerous host proteins that promote optimal RNA metabolism of the HIV-1 viral RNAs (vRNAs), such as the proteins of the DEAD-box family. The DEAD-box family of RNA helicases regulates multiple steps of RNA metabolism and processing, including transcription, splicing, nucleocytoplasmic export, trafficking, translation and turnover, mediated by their ATP-dependent RNA unwinding ability. In this review, we provide an overview of the functions and role of all DEAD-box family protein members thus far described to influence various aspects of HIV-1 vRNA metabolism. We describe the molecular mechanisms by which HIV-1 hijacks these host proteins to promote its gene expression and we discuss the implications of these interactions during viral infection, their possible roles in the maintenance of viral latency and in inducing cell death. We also speculate on the emerging potential of pharmacological inhibitors of DEAD-box proteins as novel therapeutics to control the HIV-1 pandemic.

Citing Articles

Host RNA-Binding Proteins as Regulators of HIV-1 Replication.

Giraldo-Ocampo S, Valiente-Echeverria F, Soto-Rifo R Viruses. 2025; 17(1).

PMID: 39861832 PMC: 11768693. DOI: 10.3390/v17010043.


Unveiling the DHX15-G-patch interplay in retroviral RNA packaging.

Dostalkova A, Krizova I, Junkova P, Rackova J, Kapisheva M, Novotny R Proc Natl Acad Sci U S A. 2024; 121(40):e2407990121.

PMID: 39320912 PMC: 11459146. DOI: 10.1073/pnas.2407990121.


Tough Way In, Tough Way Out: The Complex Interplay of Host and Viral Factors in Nucleocytoplasmic Trafficking during HIV-1 Infection.

Sarkar S, Balakrishnan K, Chintala K, Mohareer K, Luedde T, Vasudevan A Viruses. 2022; 14(11).

PMID: 36423112 PMC: 9696704. DOI: 10.3390/v14112503.

References
1.
Shen J, Zhang L, Zhao R . Biochemical characterization of the ATPase and helicase activity of UAP56, an essential pre-mRNA splicing and mRNA export factor. J Biol Chem. 2007; 282(31):22544-50. DOI: 10.1074/jbc.M702304200. View

2.
Yeh Y, Jenike K, Calvi R, Chiarella J, Hoh R, Deeks S . Filgotinib suppresses HIV-1-driven gene transcription by inhibiting HIV-1 splicing and T cell activation. J Clin Invest. 2020; 130(9):4969-4984. PMC: 7456222. DOI: 10.1172/JCI137371. View

3.
Sithole N, Williams C, Vaughan A, Kenyon J, Lever A . DDX17 Specifically, and Independently of DDX5, Controls Use of the HIV A4/5 Splice Acceptor Cluster and Is Essential for Efficient Replication of HIV. J Mol Biol. 2018; 430(18 Pt B):3111-3128. PMC: 6119765. DOI: 10.1016/j.jmb.2018.06.052. View

4.
Greenwood E, Williamson J, Sienkiewicz A, Naamati A, Matheson N, Lehner P . Promiscuous Targeting of Cellular Proteins by Vpr Drives Systems-Level Proteomic Remodeling in HIV-1 Infection. Cell Rep. 2019; 27(5):1579-1596.e7. PMC: 6506760. DOI: 10.1016/j.celrep.2019.04.025. View

5.
Williams C, Abbink T, Jeang K, Lever A . Identification of RNA helicases in human immunodeficiency virus 1 (HIV-1) replication - a targeted small interfering RNA library screen using pseudotyped and WT HIV-1. J Gen Virol. 2015; 96(Pt 6):1484-1489. PMC: 4635492. DOI: 10.1099/vir.0.000092. View