School of Biology and Basic Medical Science, Soochow University, Suzhou, China.
Institute of Agricultural Biotechnology and Ecological Research, Soochow University, Suzhou, China.
Front Immunol. 2022 Mar 15;13:861007. doi: 10.3389/fimmu.2022.861007. eCollection 2022.
Circular DNAs derived from single-stranded RNA viruses play important roles in counteracting viral infection. However, whether double-stranded RNA viruses generate functional circular DNAs is still unknown. Using circDNA sequencing, divergent PCR, DNA hybridization and rolling circular amplification, we presently confirmed that in silkworm, cytoplasmic polyhedrosis virus (BmCPV), a double-stranded RNA virus belonging to cypovirus, is prone to produce a BmCPV-derived circular DNA termed as vcDNA-S7. We have also found that vcDNA-S7 formation is mediated by endogenous reverse transcriptase (RT), and the proliferation of BmCPV can be inhibited by vcDNA-S7 and . Moreover, we have discovered that the silkworm RNAi immune pathway is activated by vcDNA-S7, while viral small interfering RNAs (vsiRNAs) derived from transcribed RNA by vcDNA-S7 can be detected by small RNA deep sequencing. These results suggest that BmCPV-derived vcDNA-S7, mediated by RT, can serve as a template for the biogenesis of antiviral siRNAs, which may lead to the repression of BmCPV infection. To our knowledge, this is the first demonstration that a circular DNA, produced by double stranded RNA viruses, is capable of regulating virus infection.
环状 DNA 来源于单链 RNA 病毒，在抵抗病毒感染方面发挥着重要作用。然而，双链 RNA 病毒是否能产生有功能的环状 DNA 尚不清楚。通过环状 DNA 测序、分歧 PCR、DNA 杂交和滚环扩增，我们目前证实，在桑蚕中，细胞质多角体病毒（BmCPV），一种属于 cypovirus 的双链 RNA 病毒，容易产生一种被称为 vcDNA-S7 的 BmCPV 衍生的环状 DNA。我们还发现，vcDNA-S7 的形成是由内源性逆转录酶（RT）介导的，BmCPV 的增殖可以被 vcDNA-S7 和 抑制。此外，我们发现 vcDNA-S7 激活了家蚕的 RNAi 免疫途径，而由 vcDNA-S7 转录 RNA 产生的病毒小干扰 RNA（vsiRNA）可以通过小 RNA 深度测序检测到。这些结果表明，BmCPV 衍生的 vcDNA-S7 通过 RT 介导，可以作为抗病毒 siRNA 生物发生的模板，这可能导致 BmCPV 感染的抑制。据我们所知，这是首次证明双链 RNA 病毒产生的环状 DNA 能够调节病毒感染。
