Journal article
Single-base m 6 A epitranscriptomics reveals novel HIV-1 host interaction targets in primary CD4 + T cells
Journal of virology, Vol.99(11), e01536-25
11/25/2025
DOI: 10.1128/jvi.01536-25
PMCID: PMC12645991
PMID: 41085277
Abstract
N6-methyladenosine (m6A) plays a critical role in regulating RNA stability, localization, and gene expression. m6A modification is also important for modulating the expression of viral and cellular genes during HIV-1 infection. However, the function of m6A modification in regulating HIV-1 infection of primary CD4+ T cells remains unclear. Here, we demonstrate that HIV-1 infection of activated primary CD4+ T cells promotes the interaction between the m6A writer complex subunits methyltransferase-like 3 and 14 (METTL3/METTL14). Using single-base m6A-specific RNA sequencing, we identified differentially m6A-modified cellular mRNAs in HIV-1-infected primary CD4+ T cells, including perilipin 3 (PLIN3). We also identified 30 m6A sites in HIV-1 RNA from infected primary CD4+ T cells. HIV-1 infection increased PLIN3 mRNA level and nuclear accumulation but decreased PLIN3 protein expression in primary CD4+ T cells. Polysome profiling revealed that PLIN3 mRNA was less actively translated during HIV-1 infection of primary CD4+ T cells. Furthermore, PLIN3 knockdown in primary CD4+ T cells significantly reduced HIV-1 release but enhanced virion infectivity. Our results highlight the importance of m6A RNA modification during HIV-1 infection and suggest PLIN3 as a regulatory protein of HIV-1 replication in primary CD4+ T cells.
Details
- Title: Subtitle
- Single-base m 6 A epitranscriptomics reveals novel HIV-1 host interaction targets in primary CD4 + T cells
- Creators
- Siyu Huang - University of IowaYutao Zhao - University of ChicagoStacia Phillips - University of IowaJulia E Warrick - The Ohio State UniversityMichael G Kearse - The Ohio State UniversityChuan He - University of ChicagoLi Wu - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.99(11), e01536-25
- DOI
- 10.1128/jvi.01536-25
- PMID
- 41085277
- PMCID
- PMC12645991
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Publisher
- American Society of Microbiology
- Grant note
- National Institutes of Health (NIH) AIDS Reagent Program
We thank Bethany Wilms for technical assistance and the Wu lab members for helpful discussions and suggestions. We appreciate the reagents provided by the National Institutes of Health (NIH) AIDS Reagent Program.
- Language
- English
- Electronic publication date
- 10/14/2025
- Date published
- 11/25/2025
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9985015824302771
Metrics
12 Record Views