美国UPMC希尔曼癌症中心Saumendra N. Sarkar研究组发现，寡聚腺苷酸合成酶1 (OAS1)在驱动翻译关闭和保护干扰素(IFN)产生中显示双重抗病毒机制。2024年2月28日，国际知名学术期刊《免疫》发表了这一成果。

他们发现人类(而不是小鼠)OAS1通过RNase L的典型酶活性抑制SARS-CoV-2的复制。相比之下，小鼠和人类OAS1都通过不同于典型RNase L激活的机制来保护西尼罗河病毒感染。OAS1结合特异性mRNA的富AU元素(AREs)，包括IFNβ。这种结合导致IFNβ mRNA被隔离到膜区域，导致半衰期延长和持续翻译。因此，OAS1是一种ARE结合蛋白，具有两种抗病毒活性机制:驱动翻译抑制，但也具有保护IFN表达免受翻译关闭的更广泛的非规范功能。

据介绍，在对病毒感染的反应中，细胞如何平衡翻译关闭以限制病毒复制和诱导IFN等抗病毒成分尚不清楚。IFN诱导的OAS1的不同异构体如何促进这种抗病毒反应也需要进一步阐明。

附：英文原文

Title: Oligoadenylate synthetase 1 displays dual antiviral mechanisms in driving translational shutdown and protecting interferon production

Author: Munesh K. Harioudh, Joseph Perez, Zhenlu Chong, Sharmila Nair, Lomon So, Kevin D. McCormick, Arundhati Ghosh, Lulu Shao, Rashmi Srivastava, Frank Soveg, Thomas S. Ebert, Maninjay K. Atianand, Veit Hornung, Ram Savan, Michael S. Diamond, Saumendra N. Sarkar

Issue&Volume: 2024-02-28

Abstract: In response to viral infection, how cells balance translational shutdown to limitviral replication and the induction of antiviral components like interferons (IFNs)is not well understood. Moreover, how distinct isoforms of IFN-induced oligoadenylatesynthetase 1 (OAS1) contribute to this antiviral response also requires further elucidation.Here, we show that human, but not mouse, OAS1 inhibits SARS-CoV-2 replication throughits canonical enzyme activity via RNase L. In contrast, both mouse and human OAS1protect against West Nile virus infection by a mechanism distinct from canonical RNaseL activation. OAS1 binds AU-rich elements (AREs) of specific mRNAs, including IFNβ.This binding leads to the sequestration of IFNβ mRNA to the endomembrane regions,resulting in prolonged half-life and continued translation. Thus, OAS1 is an ARE-bindingprotein with two mechanisms of antiviral activity: driving inhibition of translationbut also a broader, non-canonical function of protecting IFN expression from translationalshutdown.

DOI: 10.1016/j.immuni.2024.02.002

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00077-3