Inhibition of beta interferon transcription by noncytopathogenic bovine viral diarrhea virus is through an interferon regulatory factor 3-dependent mechanism
Inhibition of beta interferon transcription by noncytopathogenic bovine viral diarrhea virus is through an interferon regulatory factor 3-dependent mechanism
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DOI：
10.1128/jvi.76.18.8979-8988.2002
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发表时间：
2002-09-01
影响因子：
5.4
通讯作者：
McCauley, JW
中科院分区：
文献类型：
--
作者：
Baigent, SJ;Zhang, G;McCauley, JW
研究了牛病毒性腹泻病毒(BVDV)对干扰素(干扰素)应答和细胞凋亡的诱导和抑制作用。在这里，我们表明，先前感染细胞的非细胞致病性BVDV(NCP BVDV)未能阻止对α/β干扰素的转录反应。相比之下，NCP BVDV感染的细胞不能产生干扰素-α/β或mxa，以响应双链RNA(DsRNA)或感染异源病毒(Semliki森林病毒[SFV])。NCP BVDV预感染不能阻断CP BVDV或SFV诱导的细胞凋亡。分析了NCP BVDV感染对控制干扰素-β诱导途径的转录因子的影响。NCP BVDV感染后，转录因子NF-kappaB不被激活，但NCP BVDV感染不能阻断SFV或肿瘤坏死因子α对转录因子-kappaB的激活。此外，NCP BVDV感染不能导致应激蛋白(JNK1和JNK2)的激活或转录因子ATF-2和c-Jun的磷酸化，同样，NCP BVDV感染也不能阻断SFV对它们的激活。对NCP BVDV的反应表明，干扰素调节因子3(IRF-3)被转移到感染细胞的核中，尽管在核提取液中没有发现IRF-3的DNA结合。相反，在感染SFV的细胞的核提取液中观察到IRF-3-DNA复合体，但当细胞先前暴露于NCP BVDV时，该复合体的出现被阻止。我们的结论是，这种鼠疫病毒对干扰素诱导的抑制涉及到对IRF-3功能的阻断，我们推测这可能是鼠疫病毒在自然界中生存的关键特征。
The induction and inhibition of the interferon (IFN) response and apoptosis by bovine viral diarrhea virus (BVDV) has been examined. Here we show that prior infection of cells by noncytopathogenic BVDV (ncp BVDV) fails to block transcriptional responses to alpha/beta IFN. In contrast, ncp BVDV-infected cells fail to produce IFN-alpha/beta or MxA in response to double-stranded RNA (dsRNA) or infection with a heterologous virus (Semliki Forest virus [SFV]). ncp BVDV preinfection is unable to block cp BVDV- or SFV-induced apoptosis. The effects of ncp BVDV infection on the transcription factors controlling the IFN-beta induction pathway have been analyzed. The transcription factor NF-kappaB was not activated following ncp BVDV infection, but ncp BVDV infection was not able to block the activation of NF-kappaB by either SFV or tumor necrosis factor alpha. Furthermore, ncp BVDV infection did not result in the activation of stress kinases (JNK1 and JNK2) or the phosphorylation of transcription factors ATF-2 and c-Jun; again, ncp BVDV infection was not able to block their activation by SFV. Interferon regulatory factor 3 (IRF-3) was shown to be translocated to the nuclei of infected cells in response to ncp BVDV, although DNA-binding of IRF-3 was not seen in nuclear extracts. In contrast, an IRF-3-DNA complex was observed in nuclear extracts from cells infected with SFV, but the appearance of this complex was blocked when cells were previously exposed to ncp BVDV. We conclude that the inhibition of IFN induction by this pestivirus involves a block to IRF-3 function, and we speculate that this may be a key characteristic for the survival of pestiviruses in nature.