Miller Laura C, Jiang Zhihua, Sang Yongming, Harhay Gregory P, Lager Kelly M
USDA, Agricultural Research Service, National Animal Disease Center, Virus and Prion Research Unit, 1920 Dayton Avenue, Ames, IA 50010, USA.
Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA.
Vet Immunol Immunopathol. 2014 Jun 15;159(3-4):180-91. doi: 10.1016/j.vetimm.2014.02.015. Epub 2014 Mar 3.
Studies have found that a cluster of duplicated gene loci encoding the interferon-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 3000 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.
研究发现,一组编码干扰素诱导跨膜蛋白(IFITMs)家族的重复基因座对包括甲型流感病毒在内的多种病毒具有抗病毒活性。该基因家族在人类和小鼠中分别有5个和7个成员。在此,我们确认了猪IFITM1、IFITM2、IFITM3、IFITM5、IFITM1L1和IFITM1L4的当前注释,手动注释了IFITM1L2、IFITM1L3、IFITM5L、IFITM3L1和IFITM3L2,并提供了美国国家生物技术信息中心参考序列数据库(RefSeq)中未包含的表达序列标签(EST)和/或mRNA证据,以证明猪中存在IFITM6、IFITM7和一个新的类IFITM1(IFITM1LN)基因。系统发育分析显示,七个猪IFITM基因与已知具有抗病毒活性的高度保守的人类/小鼠直系同源基因。对感染甲型流感病毒(SIV)、猪伪狂犬病病毒、猪繁殖与呼吸综合征病毒或猪圆环病毒2型的猪在接种后14天(dpi)的猪气管支气管淋巴结(TBLN)进行数字基因表达标签分析(DGETP),结果表明猪IFITM家族成员之间的基因表达丰度差异显著,范围从每百万0到超过3000个标签。特别是,SIV在3 dpi时将IFITM1上调了5.9倍。贝叶斯框架在整体转录组分析中进一步将猪IFITM1和IFITM3鉴定为差异表达基因。除了作为参与同型黏附的蛋白质复合物的一个组成部分外,IFITM1还与细胞增殖调控相关的途径有关,而IFITM3则参与免疫反应。