Methods: Sinus ALI cultures were derived from individuals with and without the rs6967330 SNP. Basolateral pre-treatment with histamine was performed in half of the cultures to permeabilize the cellular tight junctions and replicate AR. Cultures were infected apically with RVC-15-GFP or mock control. Viral replication was assessed at 4 and 48 hours post-infection by fluorescence microscopy and qRT-PCR.
Results: The presence of basolateral histamine increased initial viral binding 1.7-fold specifically in patients carrying the risk allele rs6967330. Histamine also resulted in higher levels of viral replication in all patient samples by 48 hours. These effects were independent of preexisting atopy in the donors.
Conclusions: Activation of the histamine receptor has an additive effect on RV-C binding and replication in sinonasal epithelial cells; an effect enhanced in patients with the CDHR3 risk allele. Further studies will examine the mechanisms by which histamine and other allergic agonists enhance RV-C binding and what downstream inflammatory effects these changes may have.