RSV inclusion bodies formed by liquid-liquid phase separation sequester viral RNA, enabling the virus to evade degradation by the host OAS-RNase L antiviral pathway.
RSV evades host immune responses by sequestering viral RNA within liquid-liquid phase-separated inclusion bodies, preventing detection and degradation by the OAS-RNase L pathway.
Respiratory syncytial virus (RSV) infection is the major cause of severe respiratory illnesses in infants and older adults. RSV forms phase-separated biomolecular condensates called inclusion bodies (IBs), which serve as hubs for viral replication. However, the contribution of IBs to host immune response evasion remains elusive. We report that RSV IBs protect viral RNA from the 2′-5′ oligoadenylate synthetase (OAS)-RNase L pathway, a critical antiviral defense mechanism that cleaves viral and cellular RNAs. RSV infection did not activate the OAS-RNase L pathway, and ectopically activated RNase L did not suppress viral replication. In RSV-infected cells, double-stranded RNA (dsRNA) was efficiently sequestered within liquid–liquid phase separation (LLPS)-mediated IBs, rendering its detection challenging. LLPS perturbation caused dsRNA release from IBs into the cytosol. dsRNA extracted from infected cells, which lacked LLPS shielding, triggered OAS-RNase L pathway activation. Thus, LLPS-driven IBs structurally sequester viral RNA, facilitating RSV to evade RNase-dependent genomic RNA degradation mediated by the OAS-RNase L antiviral pathway.
Hwang et al. (2026) studied this question. RSV inclusion bodies formed by liquid-liquid phase separation sequester viral RNA, enabling the virus to evade degradation by the host OAS-RNase L antiviral pathway.