PLX213202

GSE135069: Antiviral potential of human IFN- subtypes against influenza H3N2 infection in human lung explants

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

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- subtypes 1, 2, 8, 14 and 17, which we identified to possess only low to intermediate antiviral activity. In contrast, our experiments provide evidence that subtypes 16, 5 and 4 suppress H3N2 replication 40 231 fold more efficiently compared to clinically approved IFN-2. We detected significantly higher induction of IV restriction factors MxA, RIG-I, OAS1 and PKR by these subtypes compared to the non-active IFN-1 but correlation of antiviral activity with the expression levels of these restriction factors was not observed.; Conclusions: Our results show that IFN- subtypes differ in their ability to repress H3N2 replication in human lung tissue and emphasize that IFN- subtypes 16, 5 and 4 have high therapeutic potential and should be further investigated for the prevention and treatment of severe infections with seasonal H3N2. SOURCE: Robert Geffers (robert.geffers@helmholtz-hzi.de) - Genome Analytics HCI - Helmholtz Centre for Infection Research