Thavachelvam Karthiga, Gad Hans Henrik, Ibsen Mikkel Søes, Desprès Philippe, Hokland Marianne, Hartmann Rune, Kristiansen Helle
1 Department of Molecular Biology and Genetics, Centre for Structural Biology, Aarhus University , Aarhus, Denmark .
J Interferon Cytokine Res. 2015 May;35(5):359-66. doi: 10.1089/jir.2014.0140. Epub 2014 Dec 17.
The oligoadenylate synthetase (OAS) proteins are traditionally considered intracellular antiviral proteins that mediate antiviral activity through the synthesis of 2'-5'-linked oligoadenylates and subsequent activation of the endoribonuclease RNase L. However, we have recently demonstrated that exogenous recombinant OAS1 is taken up by cells and reduces viral replication both in cell culture and in vivo, independent of RNase L. These results demonstrate a novel paracrine antiviral activity of OAS working in parallel with the classical RNase L pathway. In this study, we investigate the uptake kinetics of recombinant porcine OAS1 and show that it is rapidly and efficiently internalized in a manner that can be blocked by heparin. Heparin, furthermore, abolishes the antiviral activity of OAS1, demonstrating the requirement of the intracellular localization of OAS1 to inhibit the virus. In addition, we demonstrate that exogenous OAS1 affects an early step of the viral replication cycle.
传统上认为寡腺苷酸合成酶（OAS）蛋白是细胞内抗病毒蛋白，其通过合成2'-5'-连接的寡腺苷酸并随后激活核糖核酸酶RNase L来介导抗病毒活性。然而，我们最近证明，外源性重组OAS1被细胞摄取，并在细胞培养和体内均降低病毒复制，这一过程独立于RNase L。这些结果证明了OAS具有一种与经典RNase L途径并行发挥作用的新型旁分泌抗病毒活性。在本研究中，我们研究了重组猪OAS1的摄取动力学，并表明它以一种可被肝素阻断的方式迅速且有效地内化。此外，肝素消除了OAS1的抗病毒活性，证明了OAS1细胞内定位对抑制病毒的必要性。此外，我们证明外源性OAS1影响病毒复制周期的早期步骤。
