HIV Replication Is Increased by RNA Methylation METTL3/METTL14/WTAP Complex Activators
Simona Selberg, Eva Žusinaite, Koit Herodes, Neinar Seli, Esko Kankuri, Andres Merits, Mati Karelson
Abstract
High Resolution Image Download MS PowerPoint Slide The N6-methyladenosine (m 6 A) 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 m 6 A residues in the host cell mRNA was increased in the presence of these activator compounds. Importantly, the m 6 A 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.