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

doi:10.1021/acsomega.1c01626

HIV Replication Is Increased by RNA Methylation METTL3/METTL14/WTAP Complex Activators

ACS Omega. 2021 Jun 11;6(24):15957-15963. doi: 10.1021/acsomega.1c01626. eCollection 2021 Jun 22.

Authors

Simona Selberg¹, Eva Žusinaite², Koit Herodes¹, Neinar Seli³, Esko Kankuri⁴, Andres Merits², Mati Karelson¹

Affiliations

¹ Institute of Chemistry, University of Tartu, Tartu 50411, Estonia.
² Institute of Technology, University of Tartu, Tartu 50411, Estonia.
³ Chemestmed, Ltd., Tartu 50411, Estonia.
⁴ Faculty of Medicine, Department of Pharmacology, University of Helsinki, Helsinki 00014, Finland.

Abstract

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.