HIV Replication Is Increased by RNA Methylation METTL3/METTL14/WTAP Complex Activators.
Simona SelbergEva ŽusinaiteKoit HerodesNeinar SeliEsko KankuriAndres MeritsMati KarelsonPublished in: ACS omega (2021)
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.
Keyphrases
- antiretroviral therapy
- hiv positive
- hiv testing
- hiv infected
- human immunodeficiency virus
- hepatitis c virus
- hiv aids
- men who have sex with men
- small molecule
- induced apoptosis
- sars cov
- single cell
- south africa
- emergency department
- stem cells
- cell cycle arrest
- oxidative stress
- gene expression
- cell therapy
- cell death
- cell proliferation
- mesenchymal stem cells
- transcription factor
- signaling pathway
- helicobacter pylori
- toll like receptor
- drug induced
- nucleic acid
- protein protein