Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Isotope Science Centre, The University of Tokyo, Tokyo, Japan.
Sci Rep. 2020 Nov 10;10(1):19406. doi: 10.1038/s41598-020-76450-2.
Long non-coding RNAs (lncRNAs) play vital roles in the pathogenesis of infectious diseases, but the role of lncRNAs in herpes simplex virus 1 (HSV-1) infection remains unknown. Using RNA sequencing analysis, we explored lncRNAs that were highly expressed in murine retinal photoreceptor cell-derived 661W cells infected with HSV-1. U90926 RNA (522 nucleotides) was the most upregulated lncRNA detected post HSV-1 infection. The level of U90926 RNA was continuously increased post HSV-1 infection, reaching a 100-fold increase at 24 h. Cellular fractionation showed that U90926 RNA was located in the nucleus post HSV-1 infection. Downregulation of U90926 expression by RNA interference markedly suppressed HSV-1 DNA replication (80% reduction at 12 h post infection) and HSV-1 proliferation (93% reduction at 12 h post infection) in 661W cells. The survival rates of U90926-knockdown cells were significantly increased compared to those of control cells (81% and 21%, respectively; p < 0.0001). Thus, lncRNA U90926 is crucial for HSV-1 proliferation in retinal photoreceptor cells and consequently leads to host cell death by promoting HSV-1 proliferation.
长链非编码 RNA（lncRNA）在传染病的发病机制中发挥着重要作用，但 lncRNA 在单纯疱疹病毒 1（HSV-1）感染中的作用尚不清楚。我们通过 RNA 测序分析，探讨了在感染 HSV-1 的鼠视网膜感光细胞衍生 661W 细胞中高度表达的 lncRNA。U90926 RNA（522 个核苷酸）是检测到的在 HSV-1 感染后上调最明显的 lncRNA。U90926 RNA 的水平在 HSV-1 感染后持续增加，在 24 小时达到 100 倍的增加。细胞分馏显示，U90926 RNA 在 HSV-1 感染后位于细胞核内。通过 RNA 干扰下调 U90926 的表达，明显抑制了 661W 细胞中的 HSV-1 DNA 复制（感染后 12 小时减少 80%）和 HSV-1 增殖（感染后 12 小时减少 93%）。与对照细胞相比，U90926 敲低细胞的存活率显著增加（分别为 81%和 21%；p<0.0001）。因此，lncRNA U90926 对视网膜感光细胞中 HSV-1 的增殖至关重要，并通过促进 HSV-1 的增殖导致宿主细胞死亡。
