Division of Infectious Diseases, University of Colorado Denver, CO 80045, United States.
Virology. 2013 Aug 15;443(1):134-42. doi: 10.1016/j.virol.2013.05.009. Epub 2013 May 29.
Ribonuclease L (RNase L) is a type I interferon regulated factor that can significantly inhibit retroviruses in vitro and may activate cytoplasmic sensing pathways to augment adaptive immunity. However, the antiretroviral activity of RNase L remains to be validated in vivo. We investigated the role of RNaseL in counteracting Friend retrovirus (FV) infection relative to a well-described restriction factor, Apobec3. C57BL/6 wild-type (WT) and RNaseL knock-out (KO) mice exhibited similar acute FV infection levels despite significant transcriptional induction of oligoadenylate synthetase 1, which produces activators of RNase L. Apobec3 KO mice showed higher FV infection levels relative to WT mice, but deletion of RNaseL in Apobec3 KO mice did not augment FV infection. Moreover, RNaseL did not influence FV-specific IgG responses and recovery from viremia by 28 days post-infection. The results suggest that RNase L is not an evolutionarily-conserved host defense mechanism to counteract retroviruses in vivo.
核糖核酸酶 L（RNase L）是一种 I 型干扰素调节因子，能够在体外显著抑制逆转录病毒，并且可能激活细胞质感应途径来增强适应性免疫。然而，RNase L 的抗逆转录病毒活性仍有待在体内验证。我们研究了 RNaseL 在对抗 Friend 逆转录病毒（FV）感染方面的作用，与一种描述良好的限制因子 Apobec3 进行了比较。尽管明显诱导了寡聚腺苷酸合成酶 1（产生 RNase L 的激活剂），但 C57BL/6 野生型（WT）和 RNaseL 敲除（KO）小鼠表现出相似的急性 FV 感染水平。与 WT 小鼠相比，Apobec3 KO 小鼠的 FV 感染水平更高，但在 Apobec3 KO 小鼠中删除 RNaseL 并没有增加 FV 感染。此外，RNaseL 不影响 FV 特异性 IgG 反应和感染后 28 天从病毒血症中恢复。结果表明，RNase L 不是一种在体内抵抗逆转录病毒的进化保守的宿主防御机制。
