High basal expression of interferon-stimulated genes in human bronchial epithelial (BEAS-2B) cells contributes to influenza A virus resistance.
High basal expression of interferon-stimulated genes in human bronchial epithelial (BEAS-2B) cells contributes to influenza A virus resistance.
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DOI：
10.1371/journal.pone.0109023
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kuchipudi SV
中科院分区：
文献类型：
--
作者：
Seng LG;Daly J;Chang KC;Kuchipudi SV
呼吸道上皮细胞在甲型流感病毒（IAV）致病和宿主先天性应答中起着关键作用。转化的人呼吸道细胞系由于其相对方便以及与原代细胞一起工作的固有困难而广泛用于IAV与宿主相互作用的研究。然而，转化的细胞可能对病毒感染的易感性发生了改变。因此，需要正确表征不同呼吸道细胞类型对IAV感染的反应，以确保所选择的细胞系将提供与体内相关的结果。我们比较了人H1N1（A/USSR/77）IAV在正常原代人支气管上皮（NHBE）和两种常用的呼吸道上皮细胞系BEAS-2B和A549细胞中的复制动力学。我们发现，与NHBE、A549和Madin-Darby犬肾（MDCK）细胞相比，IAV在BEAS-2B细胞中的复制明显较差。BEAS-2B细胞中的IAV抗性伴随着具有干扰素（IFN）调节因子-7（IRF-7）、IFN刺激基因（STING）和IFN刺激基因（ISG）的高基础表达的活化的抗病毒状态。用pan-Janus激活激酶（JAK）抑制剂处理BEAS-2B细胞可降低IRF-7和ISG的表达，并导致IAV复制增加。因此，在IAV感染中使用高抗性BEAS-2B细胞可能不能反映IAV在体内人上皮细胞中的致细胞病变性。
Respiratory epithelial cells play a key role in influenza A virus (IAV) pathogenesis and host innate response. Transformed human respiratory cell lines are widely used in the study of IAV−host interactions due to their relative convenience, and inherent difficulties in working with primary cells. Transformed cells, however, may have altered susceptibility to virus infection. Proper characterization of different respiratory cell types in their responses to IAV infection is therefore needed to ensure that the cell line chosen will provide results that are of relevance in vivo. We compared replication kinetics of human H1N1 (A/USSR/77) IAVs in normal primary human bronchial epithelial (NHBE) and two commonly used respiratory epithelial cell lines namely BEAS-2B and A549 cells. We found that IAV replication was distinctly poor in BEAS-2B cells in comparison with NHBE, A549 and Madin-Darby canine kidney (MDCK) cells. IAV resistance in BEAS-2B cells was accompanied by an activated antiviral state with high basal expression of interferon (IFN) regulatory factor-7 (IRF-7), stimulator of IFN genes (STING) and IFN stimulated genes (ISGs). Treatment of BEAS-2B cells with a pan-Janus-activated-kinase (JAK) inhibitor decreased IRF-7 and ISG expression and resulted in increased IAV replication. Therefore, the use of highly resistant BEAS-2B cells in IAV infection may not reflect the cytopathogenicity of IAV in human epithelial cells in vivo.
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影响因子：
8
作者：
通讯作者：
--
影响因子：
9.4
作者：
Spackman, E;Senne, DA;Suarez, DL
通讯作者：
Suarez, DL
影响因子：
4
作者：
Kuchipudi, Suresh V.;Dunham, Stephen P.;Nelli, Rahul;White, Gavin A.;Coward, Vivien J.;Slomka, Marek J.;Brown, Ian H.;Chang, Kin Chow
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Chang, Kin Chow
影响因子：
3.7
作者：
Moerdyk-Schauwecker M;Shah NR;Murphy AM;Hastie E;Mukherjee P;Grdzelishvili VZ
通讯作者：
Grdzelishvili VZ
影响因子：
82.9
作者：
Stojdl, DF;Lichty, B;Bell, JC
通讯作者：
Bell, JC