SARS-CoV-2 defective viral genomes from distinct genomic regions drive divergent interferon responses.

DVGs from specific genomic hotspots in SARS-CoV-2 differentially activate interferon responses, with hotspot B DVGs inducing significantly stronger immune stimulation.

• Why it matters: Understanding how DVGs influence immune responses during natural infection is crucial for developing antiviral strategies, as their effects can be both protective and harmful depending on their origin and abundance.
• What they did: The study analyzed SARS-CoV-2 DVGs from patient samples and constructed representative DVGs from hotspots A and B, assessing their impact on viral replication and interferon induction in vitro and in human lung slices.
• The result: DVGs from hotspot B uniquely triggered robust interferon responses and altered dsRNA distribution, revealing that DVG origin influences innate immunity and highlighting potential therapeutic avenues.