Epigenetic Mechanisms of HIV-1 Persistence
Abstract
:1. Introduction
2. Epigenetic Mechanisms of HIV-1 Latency
2.1. Mechanisms of Pre-Integration Latency
2.2. Mechanisms of Post-Integration Latency
2.2.1. Nucleosome Positioning on the HIV-1 Provirus
2.2.2. Repressive Histone Marks on the HIV-1 Promoter during Latency
2.2.3. Implication of DNA Methylation in HIV-1 Latency
2.2.4. ncRNA-Mediated Mechanisms of HIV-1 Epigenetic Silencing
2.2.5. Nuclear Position of the HIV-1 Provirus
3. Epigenetic Persistence in Myeloid Lineages
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
Abbreviations
5mC | 5-methylcytosine |
ACSS2 | Acyl-coenzyme A synthetase short-chain family member 2 |
AIDS | Acquired Immunodeficiency Syndrome |
APOBEC3A | Apolipoprotein B mRNA editing enzyme catalytic subunit 3A |
ASP-1 | HIV-1 antisense protein |
ATP | Adenosine triphosphate |
BAF/PBAF | BRG1- or HBRM-associated factor/polybromo-associated BAF |
BLV | bovine leukemia virus |
BRD4 | bromodomain-containing protein 4 |
cART | combination antiretroviral therapy |
CBF-1 | C-promoter binding factor-1 |
cDNA | complementary DNA |
CGI | CpG island |
CpG | CpG dinucleotide |
CTIP2 | COUP-TF interacting protein 2 |
DHS | DNase I hypersensitive site |
DNA | Deoxyribonucleic acid |
DNMT | DNA methyltransferase |
EHMT | Euchromatin histone methyltransferase |
FACT | Facilitates Chromatin Transcription |
HAT | histone acetyltransferase |
HDAC | histone deacetylase |
HDACi | inhibitors of HDAC |
HERVs | human endogenous retroviruses |
HIC1 | Hypermethylated in cancer 1 |
HIRA | Histone Cell Cycle Regulator |
HIV | Human Immunodeficiency Virus |
HKMTs | histone lysine methyltransferases |
HMGA1 | High Mobility Group AT-hook 1 |
HMT | Histone MethylTransferase |
HP1 | heterochromatin protein 1 |
HTLV | human T-cell leukemia virus |
HUSH | Human Silencing Hub |
INI-1 | Integrase Interactor 1 |
INO80 | INO80 Complex ATPase |
KAT | lysine acetyltransferase |
LEDGF/p75 | lens epithelium-derived growth factor/transcription co-activator p75 |
lncRNA | long non-coding RNA |
LRA | Latency reversing agent |
LSD1 | lysine-specific demethylase 1 |
LSF | late SV40 factor |
LTR | long terminal repeat |
miRNA | microRNA |
MLV | murine leukemia virus |
Mnase | Micrococcal nuclease |
NCR | non-coding region |
ncRNA | non-coding RNA |
NDR | nucleosome-depleted region |
NKILA | NF-κB-interacting long non-coding RNA |
nuc | nucleosome |
NURD/Mi-2/CHD | Nucleosome Remodeling Deacetylase/Mi-2/Chromodomain Helicase DNA-binding |
PBMC | peripheral blood mononuclear cell |
PCAF | p300/CBP associated factor |
PHD | Plant homeodomain |
piRNA | piwi-interacting RNAs |
PML | promyelocytic leukemia |
PRC | Polycomb repressive complex |
PRMTs | protein arginine methyltransferases |
P-TEFb | positive transcription elongation factor B |
PTM | post-translational modification |
RNA | Ribonucleic acid |
SETDB1 | SET domain, bifurcated 1 |
SIRT1 | Sirtuin 1 |
SUV39H1 | Suppressor of variegation 3-9 homolog 1 |
SWI/SNF | Switch/Sucrose Non-Fermentable |
SWR1 | SWI2/SNF2-Related 1 Chromatin Remodeling |
TAF | TBP-associated factor |
TAR | Trans-activating responsive elements |
Tat | Trans-Activator of Transcription |
TCM | central memory CD4+ T cell |
TSS | transcription start site |
YY1 | Yin Yang 1 |
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Characteristics | Latent Reservoirs | Persistent Reservoirs |
---|---|---|
Cell type | CD4+ T cells (e.g., TCM [6], TN [19], etc.) | Myeloid cells (e.g., macrophages [22,23]), Follicular dendritic cells [24], Epithelial cells? [25] Tissue-resident memory CD4+ T cells (TRM)? [26] |
Causes for cART inefficiency | Low or no replication | Tissue localization and poor drug penetration |
Time of establishment | Early during the infection | “Mature” reservoirs |
Epigenetic mechanisms of HIV-1 gene regulation | Extensively studied | Poorly studied |
Histone Deacetylases | ||
Family | Members † | References |
Class I | HDAC1, HDAC2, HDAC3, HDAC8 | [77,78,79,80,81,82] |
Class IIa | HDAC4, HDAC5, HDAC7, HDAC9 | [83] |
Class IIb | HDAC6, HDAC10 | |
Class III (Sirtuins) | SIRT1-7 | [84] |
Class IV | HDAC11 | |
Histone Acetyltransferases | ||
Family | Members † | References |
GNAT | KAT2A/GCN5, KAT2B/PCAF | |
MYST | KAT5/TIP60, KAT6A/MOZ/MYST3, KAT6B/MORF/MYST4, KAT7/HBO1/MYST2, KAT8/MOF/MYST1 | [86] |
p300/CBP | KAT3B/p300, KAT3A/CBP | |
Histone Methyltransferases | ||
Family | Members † | References |
HKMTs | ASH1L, DOT1L, EHMT1-2, EZH1, EZH2, MLL1-4, NSD1-3, SETD1A, SETD1B, SETD2, SETD7, SMYD2-3, SUV39H1-2, SUV420H1-2 | [87,88,89,90] [46,47] [91,92] |
PRMTs | CARM1/PRMT4, PRMT1, PRMT5-7 | [93] |
Histone Demethylases | ||
Family | Members † | References |
KDM | LSD1/KDM1A, LSD2/KDM1B | |
JMJD | KDM2-8 classes that contain over 30 members, including MINA53/JMJD10 | [94] |
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Verdikt, R.; Hernalsteens, O.; Van Lint, C. Epigenetic Mechanisms of HIV-1 Persistence. Vaccines 2021, 9, 514. https://doi.org/10.3390/vaccines9050514
Verdikt R, Hernalsteens O, Van Lint C. Epigenetic Mechanisms of HIV-1 Persistence. Vaccines. 2021; 9(5):514. https://doi.org/10.3390/vaccines9050514
Chicago/Turabian StyleVerdikt, Roxane, Olivier Hernalsteens, and Carine Van Lint. 2021. "Epigenetic Mechanisms of HIV-1 Persistence" Vaccines 9, no. 5: 514. https://doi.org/10.3390/vaccines9050514
APA StyleVerdikt, R., Hernalsteens, O., & Van Lint, C. (2021). Epigenetic Mechanisms of HIV-1 Persistence. Vaccines, 9(5), 514. https://doi.org/10.3390/vaccines9050514