Nenasheva V V, Kovaleva G V, Uryvaev L V, Ionova K S, Dedova A V, Vorkunova G K, Chernyshenko S V, Khaidarova N V, Tarantul V Z
Institute of Molecular Genetics, Russian Academy of Sciences, 2 Kurchatov Square, 123182, Moscow, Russia,
Immunol Res. 2015 Jul;62(3):255-62. doi: 10.1007/s12026-015-8653-1.
In the present research, we have studied an influence of enhanced expression TRIM14 on alphavirus Sindbis (SINV, Togaviridae family) infection. In the HEK293 cells transfected with human trim14 gene (HEK-trim14), SINV yield after infection was decreased 1000-10,000 times (3-4 lg of TCD50/ml) at 24 h p.i. and considerably less (1-2 lg of TCD50/ml) at 48 h p.i. Analysis of the expression of 43 genes directly or indirectly involved in innate immune machine in HEK-trim14 non-infected cells comparing with the control (non-transfected) HEK293 cells revealed that stable trim14 transfection in HEK293 cells caused increased transcription of 18 genes (ifna, il6 (ifnβ2), isg15, raf-1, NF-kB (nf-kb1, rela, nf-kb2, relb), grb2, grb3-3, traf3ip2, junB, c-myb, pu.1, akt1, tyk2, erk2, mek2) and lowered transcription of 3 genes (ifnγ, gata1, il-17a). The similar patterns of genes expression observe in SINV-infected non-transfected HEK293 cells. However, SINV infection of HEK-trim14 cells caused inhibition of the most interferon cascade genes as well as subunits of transcription factor NF-κB. Thus, stable enhanced expression of trim14 gene in cells activates the transcription of many immunity genes and suppresses the SINV reproduction, but SINV infection of HEK-trim14 cells promotes inhibition of some genes involved in innate immune system.
在本研究中，我们研究了TRIM14过表达对甲病毒辛德毕斯病毒（SINV，披膜病毒科）感染的影响。在转染了人trim14基因的HEK293细胞（HEK-trim14）中，感染后24小时SINV产量降低了1000 - 10000倍（3 - 4 lg TCD50/ml），感染后48小时产量则显著降低（1 - 2 lg TCD50/ml）。与对照（未转染）的HEK293细胞相比，对未感染的HEK-trim14细胞中直接或间接参与先天免疫机制的43个基因的表达进行分析发现，HEK293细胞中稳定的trim14转染导致18个基因转录增加（ifna、il6（ifnβ2）、isg15、raf-1、NF-kB（nf-kb1、rela、nf-kb2、relb）、grb2、grb3-3、traf3ip2、junB、c-myb、pu.1、akt1、tyk2、erk2、mek2），3个基因转录降低（ifnγ、gata1、il-17a）。在未转染的HEK293细胞感染SINV后也观察到了类似的基因表达模式。然而，HEK-trim14细胞感染SINV会导致大多数干扰素级联基因以及转录因子NF-κB亚基受到抑制。因此细胞中trim基因的稳定过表达会激活许多免疫基因的转录并抑制SINV复制，但HEK-trim14细胞感染SINV会促进对一些参与先天免疫系统的基因的抑制。
