GSE264016 Porcine Rotavirus VP6 Protein Wrests IPEC-J2 METTL3-Mediated M6A Modification to Fight Antiviral Immune Response

Contributors : Yaxu Liang ; Xuejiao Zhu ; Ning Peng ; Xiang ZhongSeries Type : OtherOrganism : Porcine rotavirus ; Sus scrofaN6-methyladenosine (m6A), the most abundant mRNA modification, can regulate various mRNA metabolism to affect numerous physiological and pathophysiological processes, including immune function. However, the regulation of m6A methylation and its role in immune defense against virus infections remain unexplored. Here, we found that Porcine rotavirus (PoRV) infection decreased global m6A levels in host cells by downregulating m6A writer METTL3. Remarkably, knockdown of Mettl3 or m6A reader Ythdf2 enhances antiviral resistance in IPEC-J2 cells. Through RNA-seq and m6A -seq, we identified interferon regulatory factor 2 (IRF2) and interferon induced protein 44-like (IFI44L) as key m6A targets during PoRV infection. Silencing Mettl3 or Ythdf2 elevated mRNA stability of Irf2 and Ifi44l to restricting viral replication. Conversely, depletion of Irf2 and Ifi44l rendered host cells more susceptible to PoRV infection. Our findings uncover a novel m6A-mediated antiviral mechanism targeting the interferon response factors IRF2 and IFI44L, shedding new light on the epitranscriptomic regulation of host-pathogen interactions.

Source: GEO: Gene Expression Omnibus - April 19, 2024 Category: Genetics & Stem Cells Tags: Other Porcine rotavirus Sus scrofa Source Type: research