Plus-strand RNA viruses hijack Musashi homolog 1 to shield viral RNA from cytoplasmic ribonuclease degradation.

A successful strategy employed by RNA viruses to achieve replication is to evade host cell RNase degradation. However, the mechanisms through which plus-strand RNA viruses effectively shield viral RNA from cellular ribonuclease degradation remain unclear. In this study, we identified the phenomenon whereby plus-strand RNA viruses, including avian leukosis virus subgroup J (ALV-J), reticuloendotheliosis virus (REV), chicken astrovirus (CAstV), and porcine epidemic diarrhea virus (PEDV), hijacked host cellular Musashi homolog 1 (MSI1). These viruses upregulated MSI1 expression and facilitated its translocation from the cytoplasmic periphery to a position proximal to and within the nucleus, thereby protecting viral RNA from degradation. Mechanistic analyses revealed that these viruses use distinct regions, the unique (U3) region or three prime untranslated region (3'UTR), to engage with MSI1, consequently shielding their viral RNA from cytoplasmic ribonuclease degradation. These results offer significant implications for understanding the replication tactics used by plus-strand RNA viruses, thereby advancing our understanding of their biological behaviors.IMPORTANCEThe intricate interplay between RNA viruses and host cell RNA regulation encompasses viral mechanisms designed to circumvent RNase-mediated degradation. However, the specific strategies employed by plus-strand RNA viruses to shield their RNA from host ribonucleases remain inadequately characterized. In this study, Musashi homolog 1 (MSI1) is predominantly localized in the cytoplasm of normal cells, distinct from the nucleus. Following infection by plus-strand RNA viruses such as avian leukosis virus subgroup J (ALV-J), reticuloendotheliosis virus (REV), chicken astrovirus (CAstV), and porcine epidemic diarrhea virus (PEDV), these viruses hijack MSI1 to relocate near and within the nucleus. This hijacking is facilitated by specific regions, including unique or three prime untranslated regions, thereby preventing viral RNA from degradation by cytoplasmic ribonucleases. These findings have significant implications for elucidating the replication strategies of plus-strand RNA viruses, thereby advancing our understanding of their biological mechanisms.