Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Nov;33(S1):S8-S22.
doi: 10.1089/aid.2017.0180.

Host Methyltransferases and Demethylases: Potential New Epigenetic Targets for HIV Cure Strategies and Beyond

Daniela Boehm  1   2 , Melanie Ott  1   2
Affiliations
Review

Host Methyltransferases and Demethylases: Potential New Epigenetic Targets for HIV Cure Strategies and Beyond

Daniela Boehm et al. AIDS Res Hum Retroviruses. 2017 Nov.

Abstract

A successful HIV cure strategy may require reversing HIV latency to purge hidden viral reservoirs or enhancing HIV latency to permanently silence HIV transcription. Epigenetic modifying agents show promise as antilatency therapeutics in vitro and ex vivo, but also affect other steps in the viral life cycle. In this review, we summarize what we know about cellular DNA and protein methyltransferases (PMTs) as well as demethylases involved in HIV infection. We describe the biology and function of DNA methyltransferases, and their controversial role in HIV infection. We further explain the biology of PMTs and their effects on lysine and arginine methylation of histone and nonhistone proteins. We end with a focus on protein demethylases, their unique modes of action and their emerging influence on HIV infection. An outlook on the use of methylation-modifying agents in investigational HIV cure strategies is provided.

Keywords: HIV cure; demethylase inhibitors; histone demethylase; latency reactivation; methyltransferase; methyltransferase inhibitors.

PubMed Disclaimer

Conflict of interest statement

No competing financial interests exist.

Figures

<b>FIG. 1.</b>
FIG. 1.
Specificity of protein methyltransferases and demethylase LSD1 that target HIV-1-Tat at K51, R52, R53, and K71.
<b>FIG. 2.</b>
FIG. 2.
Histone lysine methyltransferases (KMT) and histone methyl marks implicated in HIV infection, showing residue-specific KMTs for H3K4/9/27/36 and H4K20. The majority of KMTs are highly specific for a single histone residue, whereas a few enzymes target multiple residues, as indicated.
<b>FIG. 3.</b>
FIG. 3.
Histone arginine methyltransferases (PRMT) and histone methyl marks implicated in HIV infection, showing residue-specific PRMTs for H3 and H4.
<b>FIG. 4.</b>
FIG. 4.
Histone demethylases and histone methyl marks implicated in HIV infection, showing residue-specific KMTs for H3K4, H3K9, and H3K27.
See this image and copyright information in PMC

References

    1. Kouzarides T: Chromatin modifications and their function. Cell 2007;128:693–705 - PubMed
    1. Allis CD, Jenuwein T: The molecular hallmarks of epigenetic control. Nat Rev Genet 2016;17:487–500 - PubMed
    1. Mbonye U, Karn J: Transcriptional control of HIV latency: Cellular signaling pathways, epigenetics, happenstance and the hope for a cure. Virology 2014;454–455:328–339 - PMC - PubMed
    1. Van Lint C, Emiliani S, Ott M, Verdin E: Transcriptional activation and chromatin remodeling of the HIV-1 promoter in response to histone acetylation. EMBO J 1996;15:1112–1120 - PMC - PubMed
    1. Budhiraja S, Famiglietti M, Bosque A, Planelles V, Rice AP: Cyclin T1 and CDK9 T-loop phosphorylation are downregulated during establishment of HIV-1 latency in primary resting memory CD4+ T cells. J Virol 2013;87:1211–1220 - PMC - PubMed

MeSH terms