Identifying XRN1 Accessory Factors and the Source of dsRNA in Measles Virus Inclusion Bodies

Measles virus (MeV) replicates in specialized cytoplasmic inclusion bodies (IBs), where double-stranded RNA (dsRNA) can activate PKR-mediated immune responses. MeV circumvents this by recruiting the host enzyme XRN1, which suppresses PKR activation and enhances viral replication, yet the factors enabling XRN1 to degrade viral RNAs that form dsRNA remain unknown. We will identify host enzymes that facilitate XRN1-mediated degradation and determine the viral RNA species that generate dsRNA structures, focusing on copy-back RNA and MeV mRNAs. Using live-cell imaging, protein depletion, and RNA analyses, we aim to define how XRN1 limits dsRNA accumulation within IBs and enables immune evasion.