Sulfolobus islandicus Employs Orc1-2-Mediated DNA Damage Response in Defense against Infection by SSV2
Sulfolobus islandicus Employs Orc1-2-Mediated DNA Damage Response in Defense against Infection by SSV2
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DOI：
10.1128/jvi.01438-22
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发表时间：
2022-12-21
影响因子：
5.4
通讯作者：
Huang，Li
中科院分区：
文献类型：
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作者：
Wang，Shaoying;She，Qunxin;Huang，Li
所有生物体都进化出DNA损伤反应（DDR）策略来应对对其基因组完整性的威胁。在响应DNA损伤，硫化叶菌islandicus激活其DDR网络，其中Orc 1 -2，古细菌Orc 1/Cdc 6超家族蛋白质的直系同源物，起着中心调节作用。在这里，我们表明，预处理紫外线照射减少病毒基因组复制在S。islandicus感染了梭状病毒SSV 2。与紫外线或DNA损伤剂4-硝基喹啉-1-氧化物（NQO）处理一样，SSV 2感染促进了forc 1 - 2的表达，并显著提高了Orc 1 -2的细胞水平。紫外线照射对病毒DNA水平的抑制作用在感染的S. islandicusorc 1 - 2缺失突变株。另一方面，与亲本株相比，forc 1 - 2的过表达使病毒基因组DNA减少约102倍。此外，作为Orc 1 -2介导的DDR响应基因的同源重组修复（HRR）的一部分，细胞聚集和细胞间DNA转移上调，而细胞分裂的基因下调。然而，HRR途径在不存在UpsA（细胞间DNA转移所必需的皮利亚基）的情况下在宿主抑制SSV 2基因组复制中保持功能。与这一发现相一致，缺乏控制upsgenes表达的通用转录激活因子TFB 3，仅中度影响SSV 2基因组复制。我们的结果表明，感染S。重要提示嗜极端生物在恶劣的生境中茁壮成长，因此它们的基因组完整性常常面临着严峻的挑战。当这些生物体的基因组受损时，它们对病毒感染的反应仍不清楚。我们发现，嗜热古菌Sulfolobus islandicus变得更抑制病毒SSV 2的基因组复制后，预感染紫外线照射比没有预处理。另一方面，像用紫外线或其他DNA损伤剂处理一样，S。SSV 2感染islandicus后，可激活Orc 1 -2介导的DNA损伤反应，包括激活同源重组修复、细胞聚集和DNA输入以及抑制细胞分裂。紫外线照射预处理对SSV 2基因组复制的抑制作用在S. orc 1 -2缺失的islandicus突变体。我们的研究结果表明，DNA损伤反应是由S。islandicus作为防御病毒感染的策略。
All living organisms have evolved DNA damage response (DDR) strategies in coping with threats to the integrity of their genome. In response to DNA damage, Sulfolobus islandicus activates its DDR network in which Orc1-2, an ortholog of the archaeal Orc1/Cdc6 superfamily proteins, plays a central regulatory role. Here, we show that pretreatment with UV irradiation reduced virus genome replication in S. islandicus infected with the fusellovirus SSV2. Like treatment with UV or the DNA-damaging agent 4-nitroquinoline-1-oxide (NQO), infection with SSV2 facilitated the expression oforc1-2and significantly raised the cellular level of Orc1-2. The inhibitory effect of UV irradiation on the virus DNA level was no longer apparent in the infected culture of an S. islandicusorc1-2deletion mutant strain. On the other hand, the overexpression oforc1-2decreased virus genomic DNA by ~102-fold compared to that in the parent strain. Furthermore, as part of the Orc1-2-mediated DDR response genes for homologous recombination repair (HRR), cell aggregation and intercellular DNA transfer were upregulated, whereas genes for cell division were downregulated. However, the HRR pathway remained functional in host inhibition of SSV2 genome replication in the absence of UpsA, a subunit of pili essential for intercellular DNA transfer. In agreement with this finding, lack of the general transcriptional activator TFB3, which controls the expression of theupsgenes, only moderately affected SSV2 genome replication. Our results demonstrate that infection of S. islandicus by SSV2 triggers the host DDR pathway that, in return, suppresses virus genome replication.IMPORTANCEExtremophiles thrive in harsh habitats and thus often face a daunting challenge to the integrity of their genome. How these organisms respond to virus infection when their genome is damaged remains unclear. We found that the thermophilic archaeon Sulfolobus islandicus became more inhibitory to genome replication of the virus SSV2 after preinfection UV irradiation than without the pretreatment. On the other hand, like treatment with UV or other DNA-damaging agents, infection of S. islandicus by SSV2 triggers the activation of Orc1-2-mediated DNA damage response, including the activation of homologous recombination repair, cell aggregation and DNA import, and the repression of cell division. The inhibitory effect of pretreatment with UV irradiation on SSV2 genome replication was no longer observed in an S. islandicus mutant lacking Orc1-2. Our results suggest that DNA damage response is employed by S. islandicus as a strategy to defend against virus infection.