Impaired antiviral response in human hepatoma cells
Impaired antiviral response in human hepatoma cells
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DOI：
10.1006/viro.1999.9983
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发表时间：
1999-10-25
期刊：
影响因子：
3.7
通讯作者：
Julkunen, I
中科院分区：
文献类型：
--
作者：
Keskinen, P;Nyqvist, M;Julkunen, I
B、C和D型肝炎病毒可以感染肝细胞，在某些个体中建立慢性感染期。目前，关于肝细胞中抗病毒机制的信息相对较少。由于没有良好的体外模型感染系统的肝炎病毒，我们已经使用甲型流感病毒，Sendal，水泡性口炎（VSV）病毒的特点干扰素（IFN）的反应和IFN诱导的抗病毒机制，在人肝癌细胞系。HepG 2或HuH 7细胞dib未显示任何可检测的IFN-α/β产生以响应甲型流感或Sendal病毒感染。用IFN-α处理细胞导致IFN-α诱导的Mx、2 '，5'-寡腺苷酸合成酶（OAS）和HLA I类基因表达的上调，但仅具有异常高的IFN-α水平（大于或等于100 IU/ml）。因此，在观察到针对这些病毒的任何可检测的抗病毒活性之前，需要高预处理水平的IFN-α，对于甲型流感病毒和VSV为1000 IU/ml，对于仙台病毒为100 IU/ml。IFN-γ对甲型流感病毒有一定的抗病毒作用，但对VSV和仙台病毒无效。IFN-γ上调HLA I类蛋白表达，而Mx或OAS表达水平没有增加。仙台病毒感染过程中，HLA I类表达有适度的上调，而甲型流感病毒感染导致，在最初的微弱上调后，在感染后期HLA I类表达明显下降。结果表明，肝癌细胞可能具有内在的能力差，产生和响应I型IFN，这可能有助于他们无法有效抵抗病毒感染。(C)北京：科学出版社.
Hepatitis B, C, and D viruses can infect liver cells and in some individuals establish a chronic phase of infection. Presently, relatively little information is available on the antiviral mechanisms in liver cells. Because no good in vitro model infection systems for hepatitis viruses are available, we have used influenza A, Sendal, and vesicular stomatitis (VSV) viruses to characterize interferon (IFN) responses and IFN-induced antiviral mechanisms in human hepatoma cell lines. HepG2 or HuH7 cells dib not show any detectable IFN-alpha/beta production in response to influenza A or Sendal virus infections. Treatment of cells with IFN-alpha resulted in upregulation of IFN-alpha-inducible Mx, 2',5'-oligoadenylate synthetase (OAS) and HLA class I gene expression but only with exceptionally high levels of IFN-alpha (greater than or equal to 100 IU/ml). Accordingly, high pretreatment levels of IFN-alpha, 1000 IU/ml for influenza A end VSV and 100 IU/ml for Sendai virus, were required before any detectable antiviral activity against these viruses was seen. IFN-gamma had some antiviral effect against influenza A virus but appeared to be ineffective against VSV and Sendai virus. IFN-gamma upregulated HLA class I protein expression, whereas Mx or OAS expression levels were not increased. There was a modest upregulation of HLA class I expression during Sendai virus infection, whereas influenza A virus infection resulted, after an initial weak upregulation, in a clear decrease in HLA class I expression at late times of infection. The results suggest that hepatoma cells may have intrinsically poor ability to produce and respond to type I IFNs, which may contribute to their inability to efficiency resist viral infections. (C) 1999 Academic Press.