Several DNA viruses have evolved antagonists to inhibit the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) DNA-sensing immune pathway. This includes DNA viral oncogenes that antagonize the cGAS-STING pathway by binding STING through the LxCxE motif. The 293T human cells are widely used in biology studies as they are highly transfectable. While parental 293 cells express high levels of STING, 293T cells lack STING and are unable to induce interferon antiviral responses to cytosolic DNA. Additionally, 293T cells express the SV40 polyomavirus large T antigen (LT) which enhances the replication of transfected DNA plasmids carrying the SV40 origin of replication. Since SV40 LT also encodes the LxCxE motif, the lack of STING expression in 293T cells is commonly assumed to be due to SV40 large T antigen. We find that SV40 LT does not alter exogenously expressed and endogenous levels of STING protein. We show that STING transcription is suppressed in 293T cells but is not driven by SV40. This study also revealed that SV40 LT does indeed inhibit cGAS-STING interferon induction, but through a mechanism distinct from other DNA virus oncogenes. Collectively, these results indicate that while SV40 LT can inhibit cGAS-STING interferon induction, it does so in an unanticipated manner.

中文翻译：

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SV40大T抗原对293T细胞中STING的丢失不负责，但可以抑制cGAS-STING干扰素的诱导。

几种DNA病毒已经进化出可以抑制环GMP-AMP合酶（cGAS）的干扰素基因刺激（STING）DNA感应免疫途径的拮抗剂。这包括通过通过LxCxE基序结合STING拮抗cGAS-STING途径的DNA病毒致癌基因。293T人类细胞具有高度转染性，因此被广泛用于生物学研究。亲本293细胞表达高水平的STING，而293T细胞缺乏STING，并且无法诱导对胞质DNA的干扰素抗病毒反应。另外，293T细胞表达SV40多瘤病毒大T抗原（LT），该抗原可增强带有SV40复制起点的转染DNA质粒的复制。由于SV40 LT也编码LxCxE基序，因此通常认为293T细胞中STING表达的缺乏是由于SV40大T抗原引起的。我们发现SV40 LT不会改变STING蛋白的外源表达和内源性水平。我们显示STING转录在293T细胞中受到抑制，但不受SV40驱动。这项研究还表明，SV40 LT确实确实抑制cGAS-STING干扰素的诱导，但是其机制不同于其他DNA病毒癌基因。总的来说，这些结果表明，尽管SV40 LT可以抑制cGAS-STING干扰素诱导，但它以意想不到的方式抑制了cGAS-STING干扰素的诱导。