Respiratory Syncytial Virus Sequesters NF-κB Subunit p65 to Cytoplasmic Inclusion Bodies To Inhibit Innate Immune Signaling.

摘要: Viruses routinely employ strategies to prevent the activation of innate immune signaling in infected cells. Respiratory syncytial virus (RSV) is no exception, as it encodes two accessory proteins (NS1 and NS2) which are well established block interferon signaling. However, RSV-encoded mechanisms for inhibiting NF-κB less characterized. In this study, we identified RSV-mediated antagonism pathway, independent NS1 NS2 indeed distinct from other known viral inhibition. both human bovine RSV-infected cells, demonstrated that p65 subunit rerouted perinuclear puncta cytoplasm, synonymous with inclusion bodies (IBs), site RNA replication. Captured was unable translocate nucleus or transactivate a reporter following tumor necrosis factor alpha (TNF-α) stimulation, confirming immune-antagonistic nature sequestration. Subsequently, used correlative light electron microscopy (CLEM) colocalize RSV N protein within (bRSV) IBs, granular, membraneless regions cytoplasm liquid organelle-like properties. Additional characterization bRSV IBs indicated although they likely formed by liquid-liquid phase separation (LLPS), have differential sensitivity hypotonic shock proportional their size. Together, these data identify novel mechanism relies on sequestration biomolecular condensate-a conserved across Orthopneumovirus genus not host-cell specific. More generally, provide additional evidence important immunomodulatory complexes cells.IMPORTANCE Many viruses replicate almost entirely cells; however, how pathogens able compartmentalize life cycle favorable conditions replication avoid litany antiviral detection remains relatively uncharacterized. manuscript, show respiratory (bRSV), infects cattle, does generating We confirm takes place bodies, meaning organelles functionally feature group (the orthopneumoviruses). Importantly, also showed capture transcription factors (in case NF-KB), blocking normal processes tell cell infected, may help us understand cause disease.