The immediate-early protein, ICP0, is essential for the resistance of herpes simplex virus to interferon-α/β
The immediate-early protein, ICP0, is essential for the resistance of herpes simplex virus to interferon-α/β
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DOI：
10.1006/viro.2001.1280
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发表时间：
2002-02-15
期刊：
影响因子：
3.7
通讯作者：
Halford, WP
中科院分区：
文献类型：
--
作者：
Härle, P;Sainz, B;Halford, WP
单纯疱疹病毒1型（HSV-1）对干扰素（IFN）-α、-β或-γ的抗病毒作用具有抗性。ICP 0（-）突变体在IFN-α/β受体敲除小鼠中像野生型病毒一样复制的事实（Leib等人，1999，J. Exp. Med.189，663）表明ICP 0可能在HSV-1对IFN的抗性中起直接作用。为了验证这一假设，将IFN-α、IFN-β和IFN-γ的作用与野生型HSV-1和ICP 0（-）突变病毒7134进行了比较。在Vero细胞中，7134对低剂量的1型IFN（-α/β）或II型IFN（-γ）的抑制作用比水泡性口炎病毒（一种研究充分的IFN敏感病毒）更敏感。在浓度为100 U/ml时，IFN-α、IFN-β或IFN-γ分别使7134噬斑形成的效率降低120倍、560倍和45倍。相比之下，没有IFN减少野生型HSV-1噬斑形成超过3倍。即使当Vero细胞以10 pfu/细胞感染时，IFN-α和IFN-β抑制7134复制超过100倍，但IFN-γ的抑制降低至小于10倍。虽然IFN-β有效地抑制了7134在原代小鼠肾和SK-N-SH细胞中的复制，但IFN-γ在这些细胞中对7134的抑制程度不可比。从腺病毒载体反式提供的ICP 0允许7134在IFN-α、IFN-β或IFN-γ存在下在Vero细胞中有效复制。虽然IFN-β或IFN-γ有效地抑制了7134中的ICP 0启动子-lacZ报告基因（即，类似于β-半乳糖苷酶活性降低60倍），ICP 0反式提供了几乎完全逆转IFN介导的7134中lacZ基因的抑制。结果表明，在体内感染细胞中ICP 0的表达率可能是决定宿主IFN是否抑制HSV-1基因组的关键。这一概念进行了讨论，根据其潜在的相关性建立潜伏HSV-1感染。(C)2002年爱思唯尔科学（美国）。
Herpes simplex virus type 1 (HSV-1) is resistant to the antiviral effects of interferon (IFN)-alpha, -beta, or -gamma. The fact that ICP0(-) mutants replicate like wild-type virus in IFN-alpha/beta receptor knockout mice (Leib et al, 1999, J. Exp. Med. 189, 663) suggested that ICP0 may serve a direct role in the resistance of HSV-1 to IFN. To test this hypothesis, the effects of IFN-alpha, -beta, and -gamma were compared against wild-type HSV-1 and an ICP0(-) mutant virus, 7134. In Vero cells, 7134 was more sensitive to inhibition by low doses of type 1 IFN (-alpha/beta) or type II IFN (-gamma) than vesicular stomatitis virus, a well-studied IFN-sensitive virus. At a concentration of 100 U/ml, IFN-alpha, -beta, or -gamma reduced the efficiency of 7134 plaque formation by 120-, 560-, and 45-fold, respectively. In contrast, none of the IFNs reduced wild-type HSV-1 plaque formation by more than 3-fold. Even when Vero cells were infected with 10 pfu per cell, IFN-alpha and -beta inhibited 7134 replication by over 100-fold, but inhibition by IFN-gamma decreased to less than 10-fold. While IFN-beta efficiently inhibited 7134 replication in primary mouse kidney and SK-N-SH cells, IFN-gamma did not inhibit 7134 to a comparable extent in these cells. ICP0 provided in trans from an adenovirus vector allowed 7134 to replicate efficiently in Vero cells in the presence of IFN-alpha, -beta, or -gamma. While IFN-beta or -gamma efficiently repressed the ICP0 promoter-lacZ reporter gene in 7134 (i.e., similar to60-fold reduction in beta-galactosidase activity), ICP0 provided in trans almost completely reversed IFN-mediated repression of the lacZ gene in 7134. The results suggest that the rate of ICP0 expression in infected cells in vivo may be critical in determining whether host IFNs repress the HSV-1 genome. This concept is discussed in light of its potential relevance to the establishment of latent HSV-1 infections. (C) 2002 Elsevier Science (USA).