Promyelocytic leukemia protein mediates interferon-based anti-herpes simplex virus 1 effects
Promyelocytic leukemia protein mediates interferon-based anti-herpes simplex virus 1 effects
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DOI：
10.1128/jvi.77.12.7101-7105.2003
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发表时间：
2003-06-01
影响因子：
5.4
通讯作者：
Roizman, B
中科院分区：
文献类型：
--
作者：
Chee, AV;Lopez, P;Roizman, B
单纯疱疹病毒（HSV）1使核结构域10（ND 10）核结构解体并分散其组织化的早幼粒细胞白血病蛋白（PML）。早期的报道显示，PML的异位过表达排除了ND 10的解聚，但对病毒复制没有影响。据报道，PML介导干扰素（IFN）和缺乏ICP 0的病毒突变体（Δ α 0突变体）的作用。为了检验HSV解聚ND 10结构并分散PML以排除IFN介导的抗病毒作用的假设，我们测试了来自模拟处理或暴露于IFN-α、IFN-γ或两者并感染野生型或Δ α 0突变病毒的鼠PML+/+和PML-/-细胞的病毒蛋白质积累和病毒产量。我们报告以下结果。(i)野生型和突变型病毒的生长水平以及病毒蛋白的积累水平在未处理的PML+/+和PML-/-细胞中没有显著差异。(ii)在感染Deltaalpha 0突变病毒的PML+/+细胞中观察到IFN-α和IFN-γ的主要作用，在感染野生型病毒的细胞中观察到更多的次要作用。干扰素对PML-/-细胞中野生型或突变型病毒的影响是最小的。(iii)IFN-α和IFN-γ的混合物比单独的IFN更有效，但同样，在PML+/+细胞中的作用比在PML-/-细胞中更剧烈。我们的结论是，由外源性IFN诱导的抗HSV状态是由PML介导的，并且病毒靶向ND 10结构并传播PML，以排除IFN诱导的抗病毒状态的建立。
Herpes simplex virus (HSV) 1 disaggregates the nuclear domain 10 (ND10) nuclear structures and disperses its organizing promyelocytic leukemia protein (PML). An earlier report showed that ectopic overexpression of PML precludes the disaggregation of ND10 but has no effect on viral replication. PML has been reported to mediate the effects of interferon (IFN) and viral mutants lacking ICP0 (Deltaalpha0 mutants). To test the hypothesis that HSV disaggregates ND10 structures and disperses PML to preclude IFN-mediated antiviral effects, we tested the accumulation of viral proteins and virus yields from murine PML+/+ and PML-/- cells mock treated or exposed to IFN-alpha, IFN-gamma, or both and infected with the wild-type or Deltaalpha0 mutant virus. We report the following results. (i) The levels of growth of wild-type and mutant viruses and of accumulation of viral proteins were not significantly different in untreated PML+/+ and PML-/- cells. (ii) Major effects of IFN-alpha and -gamma were observed in PML+/+ cells infected with the Deltaalpha0 mutant virus, and more minor effects were observed in cells infected with the wild-type virus. The effects of the IFNs on either wild-type or the mutant virus in PML-/- cells were minimal. (iii) The mixture of IFN-alpha and -gamma was more effective than either IFN alone, but again, the effect was more drastic in PML+/+ cells than in PML-/- cells. We concluded that the anti-HSV state induced by exogenous IFN is mediated by PML and that the virus targets the ND10 structures and disseminates PML in order to preclude the establishment of the antiviral state induced by IFNs.