Expression of RNA-m6A-related genes correlates with the HIV latent reservoir level and the CD4+ and CD8+T cell profiles of patients with AIDS

Cell Mol Biol (Noisy-le-grand). 2023 Apr 30;69(4):125-132. doi: 10.14715/cmb/2023.69.4.20.

Abstract

The HIV latent reservoir is the main obstacle to the eradication of AIDS. Recent studies have shown that the RNA m6A is involved in the regulation of HIV-1 replication. However, no relevant study has reported the relationship between RNA m6A and HIV latent reservoir. For this purpose, peripheral blood mononuclear cell (PBMC) was collected from 36 HIV-infected patients at 1, 24, and 48 weeks after treatment initiation. The number of CD4+ and CD8+ T cells was detected by flow cytometry. Amount of HIV DNA in the PBMC samples one week after treatment initiation was detected by Q-PCR. The expression levels of 23 RNA-m6A-related genes were detected by Q-PCR and Pearson's correlation analysis was performed. Results showed that there was a negative correlation between HIV DNA concentration and the number of CD4+ T cells (r=-0.32, p=0.05; r=-0.32, p=0.06) and a positive correlation with the number of CD8+ T cells (r=0.48, p=0.003; r=0.37, p=0.03). Furthermore, a negative correlation was observed between HIV DNA concentration and the CD4+/CD8+ T cell ratio (r=-0.53, p=0.001; r=-0.51, p=0.001). RNAm6A related genes which correlated with HIV DNA concentration includedALKBH5 (r=-0.45, p=-0.006), METTL3 (r=0.73, p=2.76e-7), METTL16 (r=0.71, p=1.21e2.76e-06), YTHDF1 (r=0.47, p=0.004). Moreover, they have different degrees of correlation with numbers ofCD4+ and CD8+ T cell subsets, and the CD4+/CD8+T cell ratio. In addition, the expression of RBM15 was not correlated with HIV DNA concentration but was significantly negatively correlated with the number of CD4+T cells (r=-0.40, p=0.02). In conclusion, the expression of ALKBH5, METTL3, and METTL16 is correlated with the HIV DNA level, the levels of CD4+ and CD8+ T cell counts, and the CD4+/CD8+ T cell ratio. RBM15 is independent of HIV DNA level and negatively correlated with the number of CD4+T cells.

MeSH terms

  • Acquired Immunodeficiency Syndrome*
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • HIV Infections* / genetics
  • HIV-1* / genetics
  • Humans
  • Leukocytes, Mononuclear
  • Methyltransferases
  • RNA

Substances

  • RNA
  • METTL3 protein, human
  • Methyltransferases
  • METTL16 protein, human