Molecular Virology Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research (IISER), Bhopal, India.
Synod Hospital Durtlang, Aizawl, Mizoram, India.
Sci Adv. 2023 Sep 8;9(36):eadh9170. doi: 10.1126/sciadv.adh9170. Epub 2023 Sep 6.
The functional consequences of circular RNA (circRNA) expression on HIV-1 replication are largely unknown. Using a customized protocol involving direct RNA nanopore sequencing, here, we captured circRNAs from HIV-1-infected T cells and identified ciTRAN, a circRNA that modulates HIV-1 transcription. We found that HIV-1 infection induces ciTRAN expression in a Vpr-dependent manner and that ciTRAN interacts with SRSF1, a protein known to repress HIV-1 transcription. Our results suggest that HIV-1 hijacks ciTRAN to exclude serine/arginine-rich splicing factor 1 (SRSF1) from the viral transcriptional complex, thereby promoting efficient viral transcription. In addition, we demonstrate that an SRSF1-inspired mimic can inhibit viral transcription regardless of ciTRAN induction. The hijacking of a host circRNA thus represents a previously unknown facet of primate lentiviruses in overcoming transmission bottlenecks.
环状 RNA（circRNA）表达对 HIV-1 复制的功能后果在很大程度上是未知的。使用涉及直接 RNA 纳米孔测序的定制方案，我们从 HIV-1 感染的 T 细胞中捕获了 circRNAs，并鉴定了 ciTRAN，一种调节 HIV-1 转录的 circRNA。我们发现 HIV-1 感染以 Vpr 依赖性方式诱导 ciTRAN 的表达，并且 ciTRAN 与 SRSF1 相互作用，SRSF1 是一种已知抑制 HIV-1 转录的蛋白质。我们的结果表明，HIV-1 劫持 ciTRAN 将丝氨酸/精氨酸丰富的剪接因子 1（SRSF1）从病毒转录复合物中排除，从而促进有效的病毒转录。此外，我们证明无论 ciTRAN 诱导如何，SRSF1 模拟物都可以抑制病毒转录。因此，宿主 circRNA 的劫持代表了灵长类慢病毒克服传播瓶颈的一个以前未知的方面。
