Innate sensor responses set a supra-unitary threshold for viral replication.

Viral replication in single cells requires a supra-unitary viral genome input, defined as VITREP, with replication occurring only above a threshold greater than one.

• Why it matters: Innate cytoplasmic sensors trigger rapid antiviral defenses, but how genome dose sets permissiveness for replication—and why tropism varies—remains unclear.
• What they did: Using single-cell analysis plus mathematical modeling and experiments, the study links VITREP to negative feedback regulators of CyVSP, including DAPK1, RIOK3, and PPP2R2A.
• The result: Model predictions were supported: downregulating NFR reduces replication, while upregulating NFR or coinfecting cells promotes replication, implying genome-dose control of innate suppression.

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