RNA granules associated with SAMD9-mediated poxvirus restriction are similar to antiviral granules in composition but do not require TIA1 for poxvirus restriction

Stress granule (SG)-like antiviral granules (AVG) had been found in some vaccinia virus infection conditions and shown to repress translation. Similar RNA granules are also associated with translational inhibition and poxvirus restriction mediated by the host restriction factor SAMD9, but their function is less clear. We studied the composition of these RNA granules by immunofluorescence and found them enriched with SG component TIA1 and viral dsRNA binding protein E3. However, TIA1 was not required for granule formation or SAMD9-mediated poxvirus restriction, in contrast to its critical role in SG formation and AVG function. The granule formation was abolished by blocking viral DNA replication or intermediate viral gene transcription, suggesting that post-replicative viral mRNA was important for granule formation. Our data show that TIA1 is not universally antiviral against poxviruses and support a model that the RNA granules are formed as the result of untranslated mRNA accumulation in viral DNA factories.