| Summary |
Determining the role of interferons in the host defence against influenza A virus
Methods: Tumor-free human lung explants were obtained from patients undergoing lung surgery at the University Hospital Muenster on the day of surgery. Tissue blocks were individually placed in a 12-well plate in RPMI medium. Virus infection of human lung tissue was performed with seasonal IV H3N2 strain A/Panama/2007/1999. RNA was prepared from tissue homogenates.
Results: RNA sequencing revealed significant transcriptional upregulation of genes encoding IFN-α subtypes α1, α2, α8, α14 and α17, which we identified to possess only low to intermediate antiviral activity. In contrast, our experiments provide evidence that subtypes α16, α5 and α4 suppress H3N2 replication 40 – 231 fold more efficiently compared to clinically approved IFN-α2. We detected significantly higher induction of IV restriction factors MxA, RIG-I, OAS1 and PKR by these subtypes compared to the non-active IFN-α1 but correlation of antiviral activity with the expression levels of these restriction factors was not observed.
Conclusions: Our results show that IFN-α subtypes differ in their ability to repress H3N2 replication in human lung tissue and emphasize that IFN-α subtypes α16, α5 and α4 have high therapeutic potential and should be further investigated for the prevention and treatment of severe infections with seasonal H3N2. |
Virus Dataset Detail
* p<0.05 ** p<0.01