CpG Methylation Profiles of HIV-1 Proviral DNA in Individuals on ART

The latent HIV-1 reservoir is comprised of stably integrated and intact proviruses with limited to no viral transcription. It has been proposed that latent infection may be maintained by methylation of pro-viral DNA. Here, for the first time, we investigate the cytosine methylation of a replication...

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Bibliographic Details
Published in:Viruses 2021-05, Vol.13 (5), p.799
Main Authors: Boltz, Valerie F., Ceriani, Cristina, Rausch, Jason W., Shao, Wei, Bale, Michael J., Keele, Brandon F., Hoh, Rebecca, Milush, Jeffrey M., Deeks, Steve G., Maldarelli, Frank, Kearney, Mary F., Coffin, John M.
Format: Article
Language:English
Subjects:
Antiretroviral drugs
Antiretroviral therapy
Bisulfite
Cloning
CpG dinucleotide methylation
CpG islands
Cytosine
Deoxyribonucleic acid
Design
DNA
DNA methylation
Drug resistance
Gene expression
Genomes
HIV
HIV latency
Human immunodeficiency virus
Infections
Latent infection
Leukemia
Leukocytes (mononuclear)
Lymph nodes
Lymphocytes T
Peripheral blood mononuclear cells
Proviruses
RNA expression
single genome sequencing
Tat protein
Transcription
transcriptional silencing
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Summary:The latent HIV-1 reservoir is comprised of stably integrated and intact proviruses with limited to no viral transcription. It has been proposed that latent infection may be maintained by methylation of pro-viral DNA. Here, for the first time, we investigate the cytosine methylation of a replication competent provirus (AMBI-1) found in a T cell clone in a donor on antiretroviral therapy (ART). Methylation profiles of the AMBI-1 provirus were compared to other proviruses in the same donor and in samples from three other individuals on ART, including proviruses isolated from lymph node mononuclear cells (LNMCs) and peripheral blood mononuclear cells (PBMCs). We also evaluated the apparent methylation of cytosines outside of CpG (i.e., CpH) motifs. We found no evidence for methylation in AMBI-1 or any other provirus tested within the 5′ LTR promoter. In contrast, CpG methylation was observed in the env-tat-rev overlapping reading frame. In addition, we found evidence for differential provirus methylation in cells isolated from LNMCs vs. PBMCs in some individuals, possibly from the expansion of infected cell clones. Finally, we determined that apparent low-level methylation of CpH cytosines is consistent with occasional bisulfite reaction failures. In conclusion, our data do not support the proposition that latent HIV infection is associated with methylation of the HIV 5′ LTR promoter.
ISSN:1999-4915
1999-4915
DOI:10.3390/v13050799