Intracellular detection of viral nucleic acids

•Viral RNA and DNA are recognized by several intracellular innate immune receptors.•RIG-I-like helicases are key sensors of viral RNA in the cytoplasm.•Cytosolic viral DNA is recognized by cGAS, inducing STING activation via cGAMP.•The sensor IFI16 detects viral DNA both in the cytoplasm and nucleus.

Successful clearance of a microbial infection depends on the concerted action of both the innate and adaptive arms of the immune system. Accurate recognition of an invading pathogen is the first and most crucial step in eliciting effective antimicrobial defense mechanisms. In recent years, remarkable progress has been made towards understanding the molecular details of how the innate immune system recognizes microbial signatures, commonly called pathogen-associated molecular patterns (PAMPs). For viral pathogens, nucleic acids — both viral genomes and viral replication products — represent a major class of PAMPs that trigger antiviral host responses via activation of germline-encoded innate immune receptors. Here we summarize recent advances in intracellular innate sensing mechanisms of viral RNA and DNA.