Wang H-F, Chen L, Luo J, He H-X
National Research Center for Wildlife-Borne Diseases, Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Cell Mol Biol (Noisy-le-grand). 2016 Nov 30;62(13):65-70. doi: 10.14715/cmb/2016.62.13.12.
The interferon-induced transmembrane (IFITM) proteins usually protect cells from many virus infections by viral entry and replication. Thus, the present study aimed to identification novel regulation factors of IFITM genes. Our data showed up-regulation of IFITM1, IFITM2, and IFITM3 genes in A549 by H5N1 virus infection. However, IFITM1 was not affected, IFITM2 and IFITM3 increases expression following different concentration H5N1 virus infection in HEK293T cells. This is the first time to find differences of IFITM1 transcription in different cells with the H5N1 virus infection. Moreover, experiments showed that H5N1 virus promotes expression of KLF4 and KLF5 in both A549 and HEK293T cells, but H5N1 virus NS1, M1, NP or PB2 alone has no obvious effect on transcription of KLF5. Overexpression of KLF5 increases transcription of IFITM1, IFITM2, and IFITM3 in A549 cells, however, it does not affect transcription of IFITM1, IFITM2, and IFITM3 in HEK293T cells. In addition, results for the first time displayed that KLF4 can up-regulate expression of IFITM5 in both A549 and HEK293T cells. In conclusion, we revealed KLF5 is involved in transcription of IFITM1, 2, and 3 thus making it a potential therapeutic activator in the future to treat viral infections through promoting the innate immune response.
干扰素诱导跨膜（IFITM）蛋白通常通过阻止病毒进入和复制来保护细胞免受多种病毒感染。因此，本研究旨在鉴定IFITM基因的新调控因子。我们的数据显示，H5N1病毒感染可使A549细胞中的IFITM1、IFITM2和IFITM3基因上调。然而，IFITM1不受影响，在HEK293T细胞中，不同浓度的H5N1病毒感染后，IFITM2和IFITM3的表达增加。这是首次发现在H5N1病毒感染的不同细胞中IFITM1转录存在差异。此外，实验表明，H5N1病毒可促进A549和HEK293T细胞中KLF4和KLF5的表达，但单独的H5N1病毒NS1、M1、NP或PB2对KLF5的转录没有明显影响。KLF5的过表达可增加A549细胞中IFITM1、IFITM2和IFITM3的转录，然而，它并不影响HEK293T细胞中IFITM1、IFITM2和IFITM3的转录。此外，结果首次显示KLF4可上调A549和HEK293T细胞中IFITM5的表达。总之，我们揭示了KLF5参与IFITM1、2和3的转录，因此使其成为未来通过促进先天免疫反应来治疗病毒感染的潜在治疗激活剂。
