Escape from transcriptional shutoff during poliovirus infection: NF-κB-responsive genes IκBa and A20.

It has been known for a long time that infection of cultured cells with poliovirus results in the overall inhibition of transcription of most host genes. We examined whether selected host genes can escape transcriptional inhibition by thiouridine marking newly synthesized host mRNAs during viral infection. Using cDNA microarrays hybridized to cDNAs made from thiolated mRNAs, a small set of host transcripts was identified and their expression verified by quantitative PCR and Northern and Western blot analyses. These transcripts were synthesized from genes that displayed enrichment for NF-κB binding sites in their promoter regions, suggesting that some NF-κB-regulated promoters can escape the virus-induced inhibition of transcription. In particular, two negative regulators of NF-κB, IκBa and A20, were upregulated during viral infection. Depletion of A20 enhanced viral RNA abundance and viral yield, arguing that cells respond to virus infection by counteracting NF-κB-induced proviral effects.