A defining hallmark of the type 1 interferons (IFNs) is their ability to interfere with virus replication. As such, viruses have evolved diverse mechanisms to subvert the antiviral effects of interferons. Herpes simplex virus type 1 (HSV-1) is a large deoxyribonucleic acid virus best known for its ability to cause cold sores in infected individuals. In cultured cells, HSV-1 is relatively resistant to the effects of IFNs. Plaque reduction assays were used to determine that the immediate early HSV-1 gene product ICP0 functions in part to ensure successful replication in the presence of an IFN-induced antiviral response. Northern blot analysis showed that in the absence of ICP0, HSV-1 transcript accumulation is significantly decreased. Finally, nuclear run-on assays demonstrated that ICP0 functions to overcome IFN-induced blocks to virus transcription. The methods used in these studies are described in detail in this section.