Post-translational Modification-Based Regulation of HIV Replication

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2018 Sep 27

PMID 30254620

Citations 18

Authors

Lin Chen

Oliver T Keppler

Christian Scholz

Affiliations

Soon will be listed here.

Abstract

Human immunodeficiency virus (HIV) relies heavily on the host cellular machinery for production of viral progeny. To exploit cellular proteins for replication and to overcome host factors with antiviral activity, HIV has evolved a set of regulatory and accessory proteins to shape an optimized environment for its replication and to facilitate evasion from the immune system. Several cellular pathways are hijacked by the virus to modulate critical steps during the viral life cycle. Thereby, post-translational modifications (PTMs) of viral and cellular proteins gain increasingly attention as modifying enzymes regulate virtually every step of the viral replication cycle. This review summarizes the current knowledge of HIV-host interactions influenced by PTMs with a special focus on acetylation, ubiquitination, and phosphorylation of proteins linked to cellular signaling and viral replication. Insights into these interactions are surmised to aid development of new intervention strategies.

Citing Articles

Comprehensive SUMO Proteomic Analyses Identify HIV Latency-Associated Proteins in Microglia.

Imbert F, Langford D Cells. 2025; 14(3).

PMID: 39937027 PMC: 11817477. DOI: 10.3390/cells14030235.

Comprehensive analysis of the succinylome in Vero cells infected with peste des petits ruminants virus Nigeria 75/1 vaccine strain.

Meng X, Zhu X, Wang X, Zhang R, Zhang Z, Sun Y BMC Vet Res. 2025; 21(1):45.

PMID: 39885502 PMC: 11784008. DOI: 10.1186/s12917-025-04496-3.

RNA-FISH for HIV Transcription/Localization Analysis.

Ramdas P, Chande A Methods Mol Biol. 2024; 2807:31-43.

PMID: 38743219 DOI: 10.1007/978-1-0716-3862-0_3.

Research progress on the N protein of porcine reproductive and respiratory syndrome virus.

Zheng Y, Li G, Luo Q, Sha H, Zhang H, Wang R Front Microbiol. 2024; 15:1391697.

PMID: 38741730 PMC: 11089252. DOI: 10.3389/fmicb.2024.1391697.

Quantitative analysis of acetylation in peste des petits ruminants virus-infected Vero cells.

Meng X, Wang X, Zhu X, Zhang R, Zhang Z, Sun Y Virol J. 2023; 20(1):227.

PMID: 37817180 PMC: 10563215. DOI: 10.1186/s12985-023-02200-1.

References

Mehle A, Goncalves J, Santa-Marta M, McPike M, Gabuzda D . Phosphorylation of a novel SOCS-box regulates assembly of the HIV-1 Vif-Cul5 complex that promotes APOBEC3G degradation. Genes Dev. 2004; 18(23):2861-6. PMC: 534646. DOI: 10.1101/gad.1249904. View

Fassati A, Goff S . Characterization of intracellular reverse transcription complexes of human immunodeficiency virus type 1. J Virol. 2001; 75(8):3626-35. PMC: 114854. DOI: 10.1128/JVI.75.8.3626-3635.2001. View

Lin C, Engelman A . The barrier-to-autointegration factor is a component of functional human immunodeficiency virus type 1 preintegration complexes. J Virol. 2003; 77(8):5030-6. PMC: 152146. DOI: 10.1128/jvi.77.8.5030-5036.2003. View

Sze A, Olagnier D, Lin R, van Grevenynghe J, Hiscott J . SAMHD1 host restriction factor: a link with innate immune sensing of retrovirus infection. J Mol Biol. 2013; 425(24):4981-94. DOI: 10.1016/j.jmb.2013.10.022. View

Zhang L, Qin J, Li Y, Wang J, He Q, Zhou J . Modulation of the stability and activities of HIV-1 Tat by its ubiquitination and carboxyl-terminal region. Cell Biosci. 2014; 4(1):61. PMC: 4201738. DOI: 10.1186/2045-3701-4-61. View

Despras E, Sittewelle M, Pouvelle C, Delrieu N, Cordonnier A, Kannouche P . Rad18-dependent SUMOylation of human specialized DNA polymerase eta is required to prevent under-replicated DNA. Nat Commun. 2016; 7:13326. PMC: 5097173. DOI: 10.1038/ncomms13326. View

Wu Y, Yoder A, Yu D, Wang W, Liu J, Barrett T . Cofilin activation in peripheral CD4 T cells of HIV-1 infected patients: a pilot study. Retrovirology. 2008; 5:95. PMC: 2576353. DOI: 10.1186/1742-4690-5-95. View

Yang X, Herrmann C, Rice A . The human immunodeficiency virus Tat proteins specifically associate with TAK in vivo and require the carboxyl-terminal domain of RNA polymerase II for function. J Virol. 1996; 70(7):4576-84. PMC: 190394. DOI: 10.1128/JVI.70.7.4576-4584.1996. View

Hemonnot B, Cartier C, Gay B, Rebuffat S, Bardy M, Devaux C . The host cell MAP kinase ERK-2 regulates viral assembly and release by phosphorylating the p6gag protein of HIV-1. J Biol Chem. 2004; 279(31):32426-34. DOI: 10.1074/jbc.M313137200. View

10.

Lusic M, Marcello A, Cereseto A, Giacca M . Regulation of HIV-1 gene expression by histone acetylation and factor recruitment at the LTR promoter. EMBO J. 2003; 22(24):6550-61. PMC: 291826. DOI: 10.1093/emboj/cdg631. View

11.

Mousnier A, Kubat N, Massias-Simon A, Segeral E, Rain J, Benarous R . von Hippel Lindau binding protein 1-mediated degradation of integrase affects HIV-1 gene expression at a postintegration step. Proc Natl Acad Sci U S A. 2007; 104(34):13615-20. PMC: 1959430. DOI: 10.1073/pnas.0705162104. View

12.

Setz C, Friedrich M, Rauch P, Fraedrich K, Matthaei A, Traxdorf M . Inhibitors of Deubiquitinating Enzymes Block HIV-1 Replication and Augment the Presentation of Gag-Derived MHC-I Epitopes. Viruses. 2017; 9(8). PMC: 5580479. DOI: 10.3390/v9080222. View

13.

Quivy V, Van Lint C . Diversity of acetylation targets and roles in transcriptional regulation: the human immunodeficiency virus type 1 promoter as a model system. Biochem Pharmacol. 2002; 64(5-6):925-34. DOI: 10.1016/s0006-2952(02)01152-8. View

14.

Barouch D, Tomaka F, Wegmann F, Stieh D, Alter G, Robb M . Evaluation of a mosaic HIV-1 vaccine in a multicentre, randomised, double-blind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys (NHP 13-19). Lancet. 2018; 392(10143):232-243. PMC: 6192527. DOI: 10.1016/S0140-6736(18)31364-3. View

15.

Kwon H, Brent M, Getachew R, Jayakumar P, Chen L, Schnolzer M . Human immunodeficiency virus type 1 Tat protein inhibits the SIRT1 deacetylase and induces T cell hyperactivation. Cell Host Microbe. 2008; 3(3):158-67. PMC: 2680745. DOI: 10.1016/j.chom.2008.02.002. View

16.

Tonini T, Bagella L, DAndrilli G, Claudio P, Giordano A . Ezh2 reduces the ability of HDAC1-dependent pRb2/p130 transcriptional repression of cyclin A. Oncogene. 2004; 23(28):4930-7. DOI: 10.1038/sj.onc.1207608. View

17.

Brun S, Solignat M, Gay B, Bernard E, Chaloin L, Fenard D . VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Retrovirology. 2008; 5:57. PMC: 2474847. DOI: 10.1186/1742-4690-5-57. View

18.

Chun T, Stuyver L, Mizell S, Ehler L, Mican J, Baseler M . Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci U S A. 1997; 94(24):13193-7. PMC: 24285. DOI: 10.1073/pnas.94.24.13193. View

19.

Jaspart A, Calmels C, Cosnefroy O, Bellecave P, Pinson P, Claverol S . GCN2 phosphorylates HIV-1 integrase and decreases HIV-1 replication by limiting viral integration. Sci Rep. 2017; 7(1):2283. PMC: 5442153. DOI: 10.1038/s41598-017-02276-0. View

20.

Armitage A, Deforche K, Chang C, Wee E, Kramer B, Welch J . APOBEC3G-induced hypermutation of human immunodeficiency virus type-1 is typically a discrete "all or nothing" phenomenon. PLoS Genet. 2012; 8(3):e1002550. PMC: 3310730. DOI: 10.1371/journal.pgen.1002550. View