Chen Yu, Liu Yanqiu, Tan Keyi, Yang Ke, Zeng Zhifeng, Guo Yu, Zhang Piaoran, Han Wenyuan
National Key Laboratory of Agricultural Microbiology and College of Life Science and Technology, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China.
Nucleic Acids Res. 2025 Jun 20;53(12). doi: 10.1093/nar/gkaf576.
Bacteria and archaea use diverse defense systems to defeat their viruses, and in turn, viruses develop anti-defense strategies to overcome the host immunity. Catalytically inactive prokaryotic Argonaute proteins constitute a family of defense systems that kill infected cells to halt viral propagation, whereas how viruses escape the pAgo (prokaryotic Argonaute) immunity remains unknown. Here, we demonstrate that an archaeal chronic virus SMV1a can evade the immunity of Saccharolobus islandicus Argonaute (SiAgo) system through early progeny release. Prompt expression of virion proteins post-infection may facilitate the early progeny release. Further, we evolved SMV1a to overcome SiAgo immunity and identified that the insertion of a repeat element drives SMV1a resistance to the SiAgo immunity at the cost of inefficient progeny production in SiAgo-deficient cells. The inserted repeat is rapidly lost when the evolved SMV1a is replicated in SiAgo-deficient cells, and efficient progeny production can be restored. The data suggest that the reversible repeat insertion adapts SMV1a to hosts with different immune backgrounds. Together, our data provide new insights into the anti-defense mechanisms of an archaeal chronic virus.
细菌和古菌利用多种防御系统来抵御病毒，反过来，病毒也会发展出反防御策略来克服宿主免疫。催化失活的原核生物Argonaute蛋白构成了一类防御系统，可杀死受感染细胞以阻止病毒传播，然而病毒如何逃避pAgo（原核生物Argonaute）免疫仍不清楚。在此，我们证明一种古菌慢性病毒SMV1a可以通过早期子代释放来逃避冰岛嗜热栖热菌Argonaute（SiAgo）系统的免疫。感染后病毒粒子蛋白的快速表达可能有助于早期子代释放。此外，我们对SMV1a进行了进化以克服SiAgo免疫，并确定插入一个重复元件可使SMV1a对SiAgo免疫产生抗性，但代价是在缺乏SiAgo的细胞中产生子代的效率低下。当进化后的SMV1a在缺乏SiAgo的细胞中复制时，插入的重复序列会迅速丢失，并且可以恢复高效的子代产生。数据表明，可逆的重复序列插入使SMV1a能够适应具有不同免疫背景的宿主。总之，我们的数据为古菌慢性病毒的反防御机制提供了新的见解。
