Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.
J Interferon Cytokine Res. 2009 Sep;29(9):559-67. doi: 10.1089/jir.2009.0072.
The mammalian reoviruses and rotaviruses have evolved specific mechanisms to evade the Type I interferon (IFN) antiviral response. Rotavirus likely represses the IFN response by at least 4 mechanisms. First, the rotavirus protein NSP1, most likely functioning as an E3 ligase, can induce proteasome-dependent degradation of the transcription factors IRF3, IRF5, and IRF7 to prevent their induction of IFN. Second, NSP1 can induce proteasome-dependent degradation of the ubiquitin ligase complex protein beta-TrCP, resulting in stabilization of I kappaB and concomitant failure of virus to activate NF-kappaB for induction of IFN. Third, rotavirus may sequester NF-kappaB in viroplasms. And fourth, rotavirus can prevent STAT1 and STAT2 nuclear translocation. The predominant mechanism for rotavirus inhibition of the IFN response is likely both rotavirus strain-specific and cell type-specific. The mammalian reoviruses also display strain-specific differences in their modulation of the IFN response. Reovirus activates RIG-I and IPS-1 for phosphorylation of IRF3. Reovirus-induced activation of MDA5 also participates in induction if IFN-beta, perhaps through activation of NF-kappaB. Reovirus likely inhibits the IFN response by at least 3 virus strain-specific mechanisms. First, the reovirus mu2 protein can induce an unusual nuclear accumulation of IRF9 and repress IFN-stimulated gene (ISG) expression, most likely by disrupting IRF9 function as part of the heterotrimeric transcription factor complex, ISGF3. Second, the reovirus sigma 3 protein can bind dsRNA and prevent activation of the latent antiviral effector protein PKR. And third, genetic approaches have identified the reovirus lambda 2 and sigma 2 proteins in virus strain-specific modulation of the IFN response, but the significance remains unclear. In sum, members of the family Reoviridae have evolved a variety of mechanisms to subvert the host's innate protective response.
哺乳动物呼肠孤病毒和轮状病毒已经进化出特定的机制来逃避 I 型干扰素 (IFN) 的抗病毒反应。轮状病毒可能通过至少 4 种机制来抑制 IFN 反应。首先，轮状病毒蛋白 NSP1，很可能作为一种 E3 连接酶，可诱导转录因子 IRF3、IRF5 和 IRF7 的蛋白酶体依赖性降解，从而阻止它们诱导 IFN。其次，NSP1 可诱导泛素连接酶复合物蛋白 β-TrCP 的蛋白酶体依赖性降解，导致 IκB 稳定，同时病毒无法激活 NF-κB 以诱导 IFN。第三，轮状病毒可能将 NF-κB 隔离在 viroplasms 中。第四，轮状病毒可以阻止 STAT1 和 STAT2 核转位。轮状病毒抑制 IFN 反应的主要机制可能既具有轮状病毒株特异性又具有细胞类型特异性。哺乳动物呼肠孤病毒在其对 IFN 反应的调节方面也表现出株特异性差异。呼肠孤病毒激活 RIG-I 和 IPS-1 以磷酸化 IRF3。呼肠孤病毒诱导的 MDA5 激活也参与了 IFN-β的诱导，可能通过激活 NF-κB。呼肠孤病毒可能通过至少 3 种病毒株特异性机制抑制 IFN 反应。首先，呼肠孤病毒 mu2 蛋白可诱导 IRF9 的异常核积累，并抑制 IFN 刺激基因 (ISG) 的表达，这很可能是通过破坏 IRF9 作为异源三聚体转录因子复合物 ISGF3 的一部分的功能来实现的。其次，呼肠孤病毒 sigma 3 蛋白可结合 dsRNA，阻止潜伏抗病毒效应蛋白 PKR 的激活。第三，遗传方法已确定呼肠孤病毒 lambda 2 和 sigma 2 蛋白在病毒株特异性调节 IFN 反应中的作用，但意义尚不清楚。总之，呼肠孤病毒科的成员已经进化出多种机制来颠覆宿主的先天保护反应。
