hMPV m6A
Description
N6-methyladenosine (m6A) modification of viral RNA can influence both viral replication and innate immune recognition, but how m6A coordinates these processes during human metapneumovirus (hMPV) infection remains incompletely understood. Here, we generated a single-nucleotide-resolution map of m6A across hMPV genomic, antigenomic, and messenger RNAs using GLORI-seq and investigated the functional consequences of perturbing m6A regulation. hMPV RNA displayed heterogeneous m6A modification patterns, and reduced METTL3 expression impaired viral RNA synthesis and virus production while being associated with decreased association of viral RNA and N protein, suggesting altered encapsidation efficiency. In parallel, hMPV infection extensively remodeled the host m6A landscape in epithelial and THP1-derived immature dendritic cell (THP1-iDC) models. Genetic and pharmacological perturbation of METTL3 produced temporally distinct effects on interferon responses and maturation in THP1-iDC, indicating that m6A regulation influences both viral and host RNA-dependent processes during infection. Importantly, virion RNA and progeny viruses generated under conditions of reduced m6A displayed enhanced immunostimulatory activity without alteration of the viral nucleotide sequence. Together, these findings identify RNA m6A as an epitranscriptomic regulatory layer linking hMPV RNA biology with host immune sensing and suggest that modulation of viral RNA methylation may provide a strategy for altering viral immunogenicity.
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Institutions
- Hangzhou Medical CollegeZhejiang, Hangzhou