2-5A accumulates to high levels in interferon-treated, vaccinia virus-infected cells in the absence of any inhibition of virus replication
2-5A accumulates to high levels in interferon-treated, vaccinia virus-infected cells in the absence of any inhibition of virus replication
复制标题
在没有任何病毒复制抑制的情况下，2-5A 在干扰素处理的牛痘病毒感染细胞中积累至高水平
DOI：
10.1128/jvi.50.1.220-228.1984
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发表时间：
1984
影响因子：
5.4
通讯作者：
I. Kerr
中科院分区：
文献类型：
--
作者：
A. P. Rice;W. K. Roberts;I. Kerr
我们研究了干扰素治疗对牛痘病毒感染的HeLa、L929和CV1细胞中病毒产量、蛋白质合成和2-5A系统的影响。在所用的培养条件下，牛痘病毒的复制对干扰素的抗病毒作用相对不敏感。在L929和HeLa细胞中，干扰素在400参考单位（r.u.）每毫升的浓度对病毒蛋白质合成、病毒诱导的宿主蛋白质合成抑制或病毒产量的影响很小：2，000 - 20，000 r.u./需要ml来抑制这些。尽管如此，在用400 r.u.处理的所有这些类型的细胞的牛痘感染期间发现高水平（高达5 μ M）的2-5A [ppp（A2 ′ p）nA; n大于或等于2]。的干扰素/ml，即，干扰素浓度太低，不能显著抑制病毒生长。在非干扰素处理的HeLa细胞（其具有高组成水平的2-5A合成酶）中也发现高水平（高达5 μ M），其中牛痘病毒复制良好。可以得出结论，在这些系统中，高水平的2-5A本身对牛痘病毒没有必要的抗病毒作用。这些结果与本实验和以前用脑心肌炎病毒得到的结果形成鲜明对比。例如，在HeLa细胞中，小于20 nM的2-5A积累，但50 r.u.的干扰素/ml（Silverman等，EUR. 124：131-138，1982）。在牛痘病毒感染的细胞中，2- 5A依赖性RNase对rRNA的特征性切割相对于2-5A积累延迟。这种延迟不是缺陷的2-5A或2- 5A依赖性RNA酶的稳定病毒诱导抑制的结果;当通过细胞提取物中2- 5A依赖性RNA酶的活化进行测定时，从细胞中提取的2-5A具有完全的生物活性，并且从牛痘病毒感染的细胞中提取的2- 5A依赖性RNA酶在体外具有完全的活性。延迟的原因尚待确定。高水平的2-5A没有观察到晚期（DNA合成依赖性）牛痘转录抑制环己酰亚胺或阿糖胞苷。唯一已知的2-5A合成酶激活剂是双链RNA。因此，2-5A的存在意味着在完整的牛痘病毒感染的细胞中晚期病毒RNA中天然存在双链结构。
We investigated the effects of interferon treatment on virus yield, protein synthesis, and the 2-5A system in vaccinia virus-infected HeLa, L929, and CV1 cells. Under the culture conditions used, vaccinia virus replication was relatively insensitive to the antiviral effects of interferon. In L929 and HeLa cells, interferon at 400 reference units (r.u.) per ml had little effect on viral protein synthesis, the virus-induced inhibition of host protein synthesis, or virus yield: 2,000 to 20,000 r.u./ml were required to inhibit these. Despite this, high levels (up to 5 microM) of 2-5A [ppp(A2'p)nA; n greater than or equal to 2] were found during vaccinia infection of all of these types of cells treated with 400 r.u. of interferon per ml, i.e., at interferon concentrations too low to inhibit significantly virus growth. High levels (up to 5 microM) were also found in non-interferon-treated HeLa cells (which have a high constitutive level of 2-5A synthetase) in which vaccinia virus replicates perfectly well. It can be concluded that high levels of 2-5A per se have no necessary antiviral effect on vaccinia virus in these systems. These results are in marked contrast to those obtained here and previously with encephalomyocarditis virus. For example, in HeLa cells less than 20 nM 2-5A accumulated, but virus replication was inhibited by 50 r.u. of interferon per ml (Silverman et al., Eur. J. Biochem. 124:131-138, 1982). The characteristic cleavage of rRNA by the 2-5A-dependent RNase was delayed relative to 2-5A accumulation in the vaccinia virus-infected cells. This delay was not the result of either defective 2-5A or of a stable virus-induced inhibition of the 2-5A-dependent RNase; 2-5A extracted from the cells had full biological activity when assayed by activation of the 2-5A-dependent RNase in cell extract, and the 2-5A-dependent RNase extracted from the vaccinia virus-infected cells was fully active in vitro. The basis for the delay remains to be determined. High levels of 2-5A were not observed when late (DNA synthesis-dependent) vaccinia transcription was inhibited by either cycloheximide or cytosine arabinoside. The only known activator of the 2-5A synthetase is double-stranded RNA. The presence of 2-5A therefore implies the natural occurrence of double-stranded structures in late viral RNA in intact vaccinia virus-infected cells.
干扰素对呼肠孤病毒的作用：呼肠孤病毒感染后小鼠 L929 细胞中干扰素诱导的蛋白激酶的激活。
影响因子：
3.7
作者：
Gupta,SL;Holmes,SL;Mehra,LL
通讯作者：
Mehra,LL