Antiretroviral Therapy Suppresses RNA N 6 -Methyladenosine Modification in Peripheral Blood Mononuclear Cells from HIV-1-Infected Individuals

Tarun Mishra; Stacia Phillips; Crystal Maldonado; Jack T Stapleton; Li Wu

doi:10.1089/AID.2024.0003

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Antiretroviral Therapy Suppresses RNA N 6 -Methyladenosine Modification in Peripheral Blood Mononuclear Cells from HIV-1-Infected Individuals

Journal article

Peer reviewed

Antiretroviral Therapy Suppresses RNA N 6 -Methyladenosine Modification in Peripheral Blood Mononuclear Cells from HIV-1-Infected Individuals

Tarun Mishra, Stacia Phillips, Crystal Maldonado, Jack T Stapleton and Li Wu

AIDS research and human retroviruses, Vol.40(9), pp.511-520

05/23/2024

DOI: 10.1089/AID.2024.0003

PMCID: PMC11535450

PMID: 38753726

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https://pmc.ncbi.nlm.nih.gov/articles/PMC11535450/pdf/aid.2024.0003.pdfView

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Abstract

RNA N6-methyladenosine (m6A) modification is important for regulating gene expression and innate immune responses to viral infection. HIV-1 in vitro infection induces a significant increase in m6A modification of cellular RNA; however, whether m6A levels of cellular RNA are affected by HIV-1 replication or by antiretroviral therapy (ART) in infected individuals remains unknown. Using dot blot or enzyme-linked immunosorbent assay, we measured RNA m6A levels of peripheral blood mononuclear cells (PBMCs) from healthy donors or HIV-1-infected individuals with or without ART. Using a reverse transcription-quantitative polymerase chain reaction array, we quantified expression levels of 84 type-I interferon (IFN-I)-responsive genes in PBMCs from some individuals of these three groups. RNA m6A levels in PBMCs from HIV-1 viremic patients (n = 10) were significantly higher (p ≤ .0001) compared with ART-treated individuals (n = 22) or 1.5-fold higher compared with healthy donors (n = 14). However, the increase in RNA m6A levels did not correlate with changes in the expression of 10 m6A-regulatory genes. We found significant upregulation and downregulation in the expression of several IFN-I-responsive genes from HIV-1 viremic patients (n = 4) and ART-treated patients (n = 6) compared with healthy donors (n = 5), respectively. Our results suggest that post-transcriptional m6A modification may contribute to the regulation of IFN-I-responsive gene expression during HIV-1 infection and ART.

peripheral blood mononuclear cells

RNA modification

HIV-1 infection

antiretroviral therapy

N6-methyladenosine

type-I interferon-responsive genes

Details

Title: Subtitle: Antiretroviral Therapy Suppresses RNA N 6 -Methyladenosine Modification in Peripheral Blood Mononuclear Cells from HIV-1-Infected Individuals
Creators: Tarun Mishra - University of Iowa
Stacia Phillips - University of Iowa
Crystal Maldonado - Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Jack T Stapleton - University of Iowa
Li Wu - Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: AIDS research and human retroviruses, Vol.40(9), pp.511-520
DOI: 10.1089/AID.2024.0003
PMID: 38753726
PMCID: PMC11535450
NLM abbreviation: AIDS Res Hum Retroviruses
eISSN: 1931-8405
Grant note: R61 AI169659 / NIAID NIH HHS R21 AI170070 / NIAID NIH HHS
Language: English
Electronic publication date: 05/23/2024
Academic Unit: Microbiology and Immunology; Infectious Diseases; Orthopedics and Rehabilitation; Internal Medicine
Record Identifier: 9984628222302771

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