College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, China.
Front Immunol. 2021 Oct 14;12:710705. doi: 10.3389/fimmu.2021.710705. eCollection 2021.
Canine influenza virus (CIV) is an emerging virus that is associated with major hidden hazards to the canine population and public health. Until now, how canine uses its innate immunity to restrict CIV replication is seldomly investigated. Recently, studies on interferon-inducible transmembrane (IFITM) of several major hosts of influenza virus (human, chicken, duck, pig) indicated it can potently restrict the viral replication. Here, the gene locus of five previously annotated canine IFITM (caIFITM) genes was determined on chromosome 18 using multiple bioinformatics strategies, provisionally designated as caIFITM1, caIFITM2a, caIFITM2b, caIFITM3, and caIFITM5. An analysis on protein sequences between caIFITM and its homologs indicated they shared the same conserved amino acids important for the antiviral activity. Expression profile analysis showed that caIFITM was constitutively expressed in tissues and MDCK cell line. After treatment with interferon or infection with influenza virus, the expression level of caIFITM increased with different degrees . An animal challenge study demonstrated CIV infection resulted in upregulation of caIFITM in beagles. caIFITMs had a similar subcellular localization to their human homologs. caIFITM1 was present at the cell surface and caIFITM3 was present perinuclearly and colocalized with LAMP1-containing compartments. Finally, we generated A549 cell lines stably expressing caIFITM and challenged them with influenza virus. The result demonstrated caIFITM1, caIFITM2a, caIFITM2b, and caIFITM3 had a potent antiviral activity against influenza virus. Our study will help better understand the evolutional pattern of IFITM and its role in the host's defense against virus infection.
犬流感病毒（CIV）是一种新兴病毒，对犬类种群和公共卫生存在重大潜在危害。到目前为止，犬类如何利用其固有免疫来限制 CIV 的复制还很少被研究。最近，对几种流感病毒主要宿主（人、鸡、鸭、猪）的干扰素诱导跨膜（IFITM）的研究表明，它可以有效地限制病毒的复制。在这里，使用多种生物信息学策略确定了五个先前注释的犬 IFITM（caIFITM）基因在染色体 18 上的基因座，暂定命名为 caIFITM1、caIFITM2a、caIFITM2b、caIFITM3 和 caIFITM5。caIFITM 与同源物的蛋白序列分析表明，它们共享对抗病毒活性很重要的相同保守氨基酸。表达谱分析显示，caIFITM 在组织和 MDCK 细胞系中持续表达。用干扰素处理或感染流感病毒后，caIFITM 的表达水平不同程度地增加。动物挑战研究表明，CIV 感染导致比格犬的 caIFITM 上调。caIFITMs 与它们的人同源物具有相似的亚细胞定位。caIFITM1 位于细胞表面，caIFITM3 位于核周，并与含有 LAMP1 的隔室共定位。最后，我们生成了稳定表达 caIFITM 的 A549 细胞系，并对其进行了流感病毒的挑战。结果表明，caIFITM1、caIFITM2a、caIFITM2b 和 caIFITM3 对流感病毒具有很强的抗病毒活性。我们的研究将有助于更好地理解 IFITM 的进化模式及其在宿主防御病毒感染中的作用。
