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

Eleven CEACAM1 splice variants have been reported in humans (20). CEACAM1 isoforms 83 (Uniprot P13688-1 to -11) can differ in the number of immunoglobulin-like domains present, in the 84 presence or absence of a transmembrane domain and/or the length of their cytoplasmic tail (i.e. L, long 85 or S, short). The full-length human CEACAM1 protein (CEACAM1-4L) consists of four extracellular 86 domains (one extracellular immunoglobulin variable-region-like (IgV-like) domain and three 87 immunoglobulin constant region 2-like (IgC2-like) domains), a transmembrane domain, and a long (L) 88 cytoplasmic tail. The long cytoplasmic tail contains two immunoreceptor tyrosine-based inhibitory 89 motifs (ITIMs) that are absent in the short form (20) Table S1 ). HPAI H5N1 infection of ATII cells 124 activated an antiviral state as evidenced by the up-regulation of numerous interferon-induced genes, 125 genes associated with pathogen defense, cell proliferation, apoptosis, and metabolism (Table 1; Table 126 S2). In the apocynin alone-treated (HA) group, a large number of genes were also significantly up-127 regulated (509 genes) or down-regulated (782 genes) ( Fig. 1A ; Table S1 ) relative to the control group. 128