Department of Pathology, University of Liège, FMV Sart Tilman B43, 4000 Liège, Belgium.
Vet Res. 2010 May-Jun;41(3):29. doi: 10.1051/vetres/2010001. Epub 2010 Jan 13.
The interferon-induced Mx proteins of vertebrates are dynamin-like GTPases, some isoforms of which can additionally inhibit the life cycle of certain RNA viruses. Here we show that the porcine Mx1 protein (poMx1) inhibits replication of influenza A virus and we attempt to identify the step at which the viral life cycle is blocked. In infected cells expressing poMx1, the level of transcripts encoding the viral nucleoprotein is significantly lower than normal, even when secondary transcription is prevented by exposure to cycloheximide. This reveals that a pretranscriptional block participates to the anti-influenza activity. Binding and internalization of incoming virus particles are normal in the presence of poMx1 but centripetal traffic to the late endosomes is interrupted. Surprisingly but decisively, poMx1 significantly alters binding of early endosome autoantigen 1 to early endosomes and/or early endosome size and spatial distribution. This is compatible with impairment of traffic of the endocytic vesicles to the late endosomes.
脊椎动物的干扰素诱导的 Mx 蛋白是类似于动力蛋白的 GTP 酶，其中一些同工型还可以抑制某些 RNA 病毒的生命周期。在这里，我们表明猪 Mx1 蛋白（poMx1）可以抑制甲型流感病毒的复制，并且我们试图确定病毒生命周期被阻断的步骤。在表达 poMx1 的感染细胞中，编码病毒核蛋白的转录本的水平明显低于正常水平，即使通过用细胞松弛素 D 处理来防止二次转录也是如此。这表明转录前阻断参与了抗流感活性。在存在 poMx1 的情况下，病毒颗粒的进入和内化是正常的，但是向晚期内体的向心运输被中断。令人惊讶但却是决定性的是，poMx1 显著改变了早期内体自身抗原 1 与早期内体的结合以及/或早期内体的大小和空间分布。这与内体小泡向晚期内体的运输受损相一致。
