Deep sequencing of primary human lung epithelial cells challenged with H5N1 influenza virus reveals a proviral role for CEACAM1

Siying Ye; Chris Cowled; Cheng-Hon Yap; John Stambas

The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/324723 doi: bioRxiv preprint low pathogenic A/HongKong/X31 H3N2 virus (6). Our HiSeq analysis of HPAI H5N1 virus gene 182 transcription ( Fig. 2G ) showed that although there was a trend for increased influenza virus gene 183 expression following apocynin treatment, with only influenza non-structural (NS) gene expression 184 statistically significant. 185 186 Enrichment of antiviral and immune response genes in HPAI H5N1-infected ATII cells. 187 GO enrichment analysis was performed on genes that were significantly upregulated following HPAI 188 H5N1 infection in ATII cells in the presence or absence of apocynin to identify over-presented GO 189 terms. Many of the H5N1-upregulated genes were broadly involved in defense response 190 (GO:0006952), response to external biotic stimulus (GO:0043207), immune system processes 191 (GO:0002376), cytokine-mediated signaling pathway (GO:0019221) and type I interferon signaling 192 pathway (GO:0060337) ( Table 1; Table S2 ). In addition, many of the H5N1-upregulated genes mapped 193 to metabolic pathways (hsa01100), cytokine-cytokine receptor interaction (hsa04060), Influenza A 194 (hsa05164), TNF signaling (hsa04668) or to Jak-STAT signaling (hsa04630) (Table S3 ). However, not 195 all the H5N1-upregulated genes in these pathways were inhibited by apocynin treatment as mentioned 196 above ( Table 2; CEACAM5, were not affected by H5N1 infection (Fig. 3B ). It is also worth noting that more reads were 203 obtained for CEACAM5 (>1000 FPKM) than CEACAM1 (~ 7 FPKM) in uninfected ATII cells (Fig. 3A 204 and B), which is consistent with their normal expression patterns in human lung tissue (30). Although 205 All rights reserved. No reuse allowed without permission.