RIBOSOME COLLISIONS AT THE HOST–PATHOGEN INTERFACE: EVIDENCE LINKING TRANSLATIONAL STRESS TO INNATE IMMUNE OUTCOMES

Ribosome collisions are increasingly invoked in infection biology, but translational arrest, physical collision, stress-kinase activation and host protection are often treated as interchangeable observations. This critical narrative review asks when translation damage is causally linked to innate-immune outcome. Targeted PubMed searches updated through 13 October 2026 prioritized primary studies with direct disome or structural evidence, pathway perturbation, genetic epistasis and infection or tissue endpoints. We distinguish pausing, stalling and physical collision, then integrate EDF1–GIGYF2–4EHP initiation control, ZNF598–ASCC/RQT and PELO–HBS1L–ABCE1 rescue, NEMF–LTN1 nascent-chain disposal, and ZAKα- and GCN2-dependent signalling. Antiviral effectors can generate stall- and collision-prone states: OAS–RNase L leaves translated cleavage products that form terminal stalls and, where ribosome density permits, collisions, whereas viperin-derived ddhCTP induces a ZAK–GCN2-dependent translational brake in defined flavivirus models. Pathogens can damage rRNA or eEF2, engineer structured pause sites, suppress ribosome influx or exploit quality-control-mediated recycling. Across these settings, collision is neither intrinsically antiviral nor synonymous with inflammation. We therefore separate causal confidence from biological relevance in a two-axis C0–C4/R0–R3 framework and use a traffic-and-threshold synthesis in which ribosome influx, lesion lifetime, rescue capacity, cell lineage and coincident pattern-recognition signals shape repair, adaptation, inflammatory alarm or cell death. Current evidence establishes collision-dependent immune signalling in only a limited set of systems; in many others, collision remains inferred from stall- or stress-associated readouts. Ribosome collision is therefore not a pathogen-specific receptor but one physical state within a broader translation-surveillance network that can couple damage to stress and innate-immune outputs.