Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 3, 2014
Publication Date: June 15, 2014
Citation: Miller, L.C., Jiang, Z., Sang, Y., Harhay, G.P., Lager, K.M. 2014. Evolutionary characterization of pig interferon-inducible transmembrane gene family and member expression dynamics in tracheobronchial lymph nodes of pigs infected with swine respiratory disease viruses. Veterinary Immunology and Immunopathology. 159(3-4):180-191. Interpretive Summary: Influenza virus causes a highly contagious respiratory disease with potentially fatal outcomes in both humans and animals. We identified and compared gene expression changes in tracheobronchial lymph node of pigs following a comparative study of respiratory viral infection. Our analysis clearly demonstrated that multiple interferon-induced genes were differentially expressed over a 14-day study post-inoculation. Our further characterization of the porcine interferon-induced genes and genomic organization led us to find 7 distinct genes that have potential antiviral functions against influenza in the pig. These findings may someday be used by veterinarians to guide improved influenza control programs in pigs.
Technical Abstract: Studies have found that a cluster of duplicated gene loci encoding the interferon26 inducible transmembrane proteins (IFITMs) family have antiviral activity against several viruses, including influenza A virus. The gene family has 5 and 7 members in humans and mice, respectively. Here, we confirm the current annotation of pig IFITM1, IFITM2, IFITM3, IFITM5, IFITM1L1 and IFITM1L4, manually annotated IFITM1L2, IFITM1L3, IFITM5L, IFITM3L1 and IFITM3L2, and provide expressed sequence tag (EST) and/or mRNA evidence, not contained with the NCBI Reference Sequence database (RefSeq), for the existence of IFITM6, IFITM7 and a new IFITM1-like (IFITM1LN) gene in pigs. Phylogenic analyses showed seven porcine IFITM genes with highly conserved human/mouse orthologs known to have anti-viral activity. Digital Gene Expression Tag Profiling (DGETP) of swine tracheobronchial lymph nodes (TBLN) of pigs infected with swine influenza virus (SIV), porcine pseudorabies virus, porcine reproductive and respiratory syndrome virus or porcine circovirus type 2 over 14 days post-inoculation (dpi) showed that gene expression abundance differs dramatically among pig IFITM family members, ranging from 0 to over 3,000 tags per million. In particular, SIV up regulated IFITM1 by 5.9 fold at 3 dpi. Bayesian framework further identified pig IFITM1 and IFITM3 as differentially expressed genes in the overall transcriptome analysis. In addition to being a component of protein complexes involved in homotypic adhesion, the IFITM1 is also associated with pathways related to regulation of cell proliferation and IFITM3 is involved in immune responses.