Single-base m 6 A epitranscriptomics reveals novel HIV-1 host interaction targets in primary CD4 + T cells

作者：Siyu Huang, Yutao Zhao, Stacia Phillips, Julia E. Warrick, Michael G. Kearse, Chuan He, Li Wu · 发表于：Journal of Virology · 年份：2025 · DOI：10.1128/jvi.01536-25 · 被引用次数：4 · 研究领域：RNA modifications and cancer、RNA Research and Splicing、HVDC Systems and Fault Protection

ABSTRACT N 6 -methyladenosine (m 6 A) plays a critical role in regulating RNA Ostability, localization, and gene expression. m 6 A modification is also important for modulating the expression of viral and cellular genes during HIV-1 infection. However, the function of m 6 A 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 m 6 A writer complex subunits methyltransferase-like 3 and 14 (METTL3/METTL14). Using single-base m 6 A-specific RNA sequencing, we identified differentially m 6 A-modified cellular mRNAs in HIV-1-infected primary CD4 + T cells, including perilipin 3 ( PLIN3 ). We also identified 30 m 6 A 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 m 6 A RNA modification during HIV-1 infection and suggest PLIN3 as a regulatory protein of HIV-1 replication in primary CD4 + T cells. IMPORTANCE m 6 A is a common chemical modification on mRNA that regulates RNA stability, localization, and gene expression. m 6...