METTL3 depletion blocks vesicular stomatitis virus replication in pancreatic cancer cells through the establishment of an intrinsic antiviral state.

ABSTRACT: Vesicular stomatitis virus (VSV) is a promising oncolytic virus (OV) against different malignancies, including pancreatic ductal adenocarcinoma (PDAC). In this study, we examined the role of methyltransferase-like 3 (METTL3), a catalytic subunit of the cellular writer complex that is responsible for N6-methyladenosine (m6A) RNA modification, as a potential host factor of VSV replication in PDAC cells. METTL3 was previously shown to be upregulated in PDAC, where it promotes cancer cell proliferation, invasion, and chemoresistance. The impact of METTL3 on life cycles of different viruses varies depending on both the virus and the cell type. Additionally, METTL3 plays a positive role in VSV replication in non-PDAC cells via m6A modification of VSV RNAs, which attenuates innate antiviral respo

SUBMITTER: Catacalos-Goad C 

PROVIDER: S-EPMC12090749 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature