Inhibition of infectious pancreatic necrosis virus replication by Atlantic salmon Mx1 protein

Inhibition of infectious pancreatic necrosis virus replication by Atlantic salmon Mx1 protein
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DOI:
10.1128/jvi.78.15.7938-7944.2004
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发表时间:
2004-08-01
影响因子:
5.4
通讯作者:
Robertsen, B
Robertsen, B
中科院分区:
医学2区
文献类型:
--
作者:
Larsen, R;Rokenes, TP;Robertsen, B

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在哺乳动物和鸡中,MX蛋白形成干扰素诱导的GTP酶家族,对多种单链RNA病毒具有很强的抗病毒活性。在FISH中,α/β干扰素已被报道能抑制传染性胰腺坏死病毒(IPNV)的复制,但其作用机制尚未阐明。然而,已经观察到抑制IPNV和Mx蛋白表达之间的相关性。为研究大西洋鲑鱼Mx1蛋白(ASMx1)是否具有抗IPNV活性,建立了ASMx1的CHSE-214细胞。ASMx1似乎定位于细胞质中。所选择的ASMx1表达克隆显示出IPNV诱导的细胞病变效应严重降低,这一点从病毒产量减少500倍得到证实。通过抑制病毒蛋白合成和减少病毒转录本的积累,进一步证实了其抗IPNV活性。目前的工作进一步增加了证据,表明抗病毒活性是脊椎动物Mx蛋白的主要功能作用。此外,被Mx蛋白抑制的病毒列表被扩展到包括双链RNA病毒。
Mx proteins form a family of interferon (IFN)-induced GTPases with potent antiviral activity against various single-stranded RNA viruses in mammals and chickens. In fish, alpha/beta IFN has been reported to inhibit the replication of infectious pancreatic necrosis virus (IPNV), but the mode of action has not been elucidated. A correlation between the inhibition of IPNV and Mx protein expression has, however, been observed. To examine whether Atlantic salmon Mx1 protein (ASMx1) possesses antiviral activity against IPNV, CHSE-214 cells constitutively expressing ASMx1 were established. ASMx1 appeared to be localized in the cytoplasm. The ASMx1-expressing clone selected showed a severely reduced IPNV-induced cytopathic effect, which was confirmed by a 500-fold reduction in virus yield. The antiviral activity against IPNV was further confirmed by the inhibition of virus protein synthesis and the reduced accumulation of virus transcripts. The present work further adds to the body of evidence which suggests that antiviral activity is a major functional role of vertebrate Mx proteins. Moreover, the list of viruses inhibited by Mx proteins is extended to include double-stranded RNA viruses.