The N6-methyladenosine (m6A) modifications in both viral and host cell RNAs play an important role in HIV-1 virus genome transcription and virus replication. We demonstrate here that activators of the METTL3/METTL14/WTAP RNA methyltransferase complex enhance the production of virus particles in cells harboring HIV-1 provirus. In parallel, the amount of m6A residues in the host cell mRNA was increased in the presence of these activator compounds. Importantly, the m6A methylation of the HIV-1 RNA was also enhanced significantly (about 18%). The increase of virus replication by the small-molecule activators of the METTL3/METTL14/WTAP complex excludes them as potential anti-HIV-1 drug candidates. However, the compounds may be of large interest as activators for the latent HIV-1 provirus copies deposited in host cells' genome and the subsequent virus eradication by an antiviral compound.
CITATION STYLE
Selberg, S., Žusinaite, E., Herodes, K., Seli, N., Kankuri, E., Merits, A., & Karelson, M. (2021). HIV Replication Is Increased by RNA Methylation METTL3/METTL14/WTAP Complex Activators. ACS Omega, 6(24), 15957–15963. https://doi.org/10.1021/acsomega.1c01626
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