Biomolecular Science and Engineering Program, University of California, Santa Barbara, CA 93106, USA.
Virology. 2010 Jan 20;396(2):316-22. doi: 10.1016/j.virol.2009.10.026. Epub 2009 Nov 12.
Two size forms of ADAR1 adenosine deaminase are known, one constitutively expressed (p110) and the other interferon (IFN)-induced (p150). To test the role of ADAR1 in viral infection, HeLa cells with ADAR1 stably knocked down and 293 cells overexpressing ADAR1 were utilized. Overexpression of p150 ADAR1 had no significant effect on the yield of vesicular stomatitis virus. Likewise, reduction of p110 and p150 ADAR1 proteins to less than approximately 10 to 15% of parental levels (ADAR1-deficient) had no significant effect on VSV growth in the absence of IFN treatment. However, inhibition of virus growth following IFN treatment was approximately 1 log(10) further reduced compared to ADAR1-sufficient cells. The level of phosphorylated protein kinase PKR was increased in ADAR1-deficient cells compared to ADAR1-sufficient cells following IFN treatment, regardless of viral infection. These results suggest that ADAR1 suppresses activation of PKR and inhibition of VSV growth in response to IFN treatment.
已知 ADAR1 腺苷脱氨酶有两种大小形式，一种是组成型表达的（p110），另一种是干扰素（IFN）诱导的（p150）。为了测试 ADAR1 在病毒感染中的作用，我们利用 ADAR1 稳定敲低的 HeLa 细胞和过表达 ADAR1 的 293 细胞进行了实验。p150 ADAR1 的过表达对水疱性口炎病毒的产量没有显著影响。同样，将 p110 和 p150 ADAR1 蛋白减少到亲本水平的约 10%至 15%（ADAR1 缺陷），在没有 IFN 处理的情况下，对 VSV 的生长也没有显著影响。然而，与 ADAR1 充足的细胞相比，IFN 处理后病毒生长的抑制作用降低了约 1 个对数（10）。与 ADAR1 充足的细胞相比，IFN 处理后 ADAR1 缺陷细胞中磷酸化蛋白激酶 PKR 的水平增加，无论是否存在病毒感染。这些结果表明，ADAR1 抑制了 PKR 的激活和 IFN 处理后 VSV 生长的抑制。
