Oligoadenylate synthetases-like (OASL) protein exerts various effects on DNA and RNA viruses by inhibiting cGAS-mediated IFN production and by enhancing RIG-I-mediated IFN induction, respectively. In this study, we aimed to examine the role of OASL in pseudorabies virus (PRV) proliferation and investigate the function of the PRV UL24 protein in cellular innate immunity. We found that OASL regulates PRV proliferation by enhancing RIG-I signaling. PRV infection decreased the expression of OASL at both the mRNA and protein levels in PK15 and HeLa cells. OASL expression suppressed the proliferation of PRV in a RIG-I-dependent manner and boosted RIG-I-mediated IFN expression as well as IFN-stimulated gene (ISG) induction. In contrast, knockdown of OASL enhanced PRV proliferation and reduced RIG-I signaling. However, the PRV UL24 protein was found to impair RIG-I signaling, thus inhibiting transcription of IFN and ISGs. In addition, the UL24 protein reduced RIG-I-induced expression of endogenous OASL in an IRF3-dependent manner, thereby antagonizing the OASL antiviral effect. Taken together, our findings characterize the role of OASL in PRV proliferation and provide new insights into the role of UL24 in PRV pathogenesis.

寡腺苷酸合成酶样 (OASL) 蛋白分别通过抑制 cGAS 介导的 IFN 产生和增强 RIG-I 介导的 IFN 诱导对 DNA 和 RNA 病毒产生各种影响。在这项研究中，我们旨在检查 OASL 在伪狂犬病毒 (PRV) 增殖中的作用，并研究 PRV UL24 蛋白在细胞先天免疫中的功能。我们发现 OASL 通过增强 RIG-I 信号传导来调节 PRV 增殖。PRV 感染降低了 OASL 在 PK15 和 HeLa 细胞中 mRNA 和蛋白质水平的表达。OASL 表达以依赖于 RIG-I 的方式抑制 PRV 的增殖，并增强了 RIG-I 介导的 IFN 表达以及 IFN 刺激基因 (ISG) 的诱导。相比之下，OASL 的敲低增强了 PRV 增殖并减少了 RIG-I 信号传导。然而，发现 PRV UL24 蛋白会损害 RIG-I 信号传导，从而抑制 IFN 和 ISG 的转录。此外，UL24蛋白以IRF3依赖性方式降低RIG-I诱导的内源性OASL的表达，从而拮抗OASL的抗病毒作用。总之，我们的研究结果描述了 OASL 在 PRV 增殖中的作用，并为 UL24 在 PRV 发病机制中的作用提供了新的见解。