2. Academic Validation
  3. HIV Replication Is Increased by RNA Methylation METTL3/METTL14/WTAP Complex Activators

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.
Simona Selberg 1,  Eva Žusinaite 2,  Koit Herodes 1,  Neinar Seli 3,  Esko Kankuri 4,  Andres Merits 2,  Mati Karelson 1
Affiliations

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.
PMID: 34179640 DOI: 10.1021/acsomega.1c01626
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.

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