Infection Biology Unit, German Primate Center, Göttingen, Germany.
Faculty of Biology and Psychology, University Göttingen, Göttingen, Germany.
Sci Rep. 2021 Oct 14;11(1):20477. doi: 10.1038/s41598-021-99691-1.
Influenza A virus (IAV) infection constitutes a significant health threat. Defective interfering particles (DIPs) can arise during IAV infection and inhibit spread of wild type (WT) IAV. DIPs harbor defective RNA segments, termed DI RNAs, that usually contain internal deletions and interfere with replication of WT viral RNA segments. Here, we asked whether DIPs harboring two instead of one DI RNA exert increased antiviral activity. For this, we focused on DI RNAs derived from segments 1 and 3, which encode the polymerase subunits PB2 and PA, respectively. We demonstrate the successful production of DIPs harboring deletions in segments 1 and/or 3, using cell lines that co-express PB2 and PA. Further, we demonstrate that DIPs harboring two instead of one DI RNA do not exhibit increased ability to inhibit replication of a WT RNA segment. Similarly, the presence of two DI RNAs did not augment the induction of the interferon-stimulated gene MxA and the inhibition of IAV infection. Collectively, our findings suggest that the presence of multiple DI RNAs derived from genomic segments encoding polymerase subunits might not result in increased antiviral activity.
甲型流感病毒（IAV）感染构成了重大的健康威胁。在 IAV 感染过程中可能会出现缺陷干扰颗粒（DIP），并抑制野生型（WT）IAV 的传播。DIP 携带有缺陷的 RNA 片段，称为 DI RNA，通常包含内部缺失，并干扰 WT 病毒 RNA 片段的复制。在这里，我们想知道是否存在两个而不是一个 DI RNA 的 DIP 会发挥出更强的抗病毒活性。为此，我们专注于来自片段 1 和 3 的 DI RNA，它们分别编码聚合酶亚基 PB2 和 PA。我们使用共表达 PB2 和 PA 的细胞系成功生产出携带 1 号和/或 3 号片段缺失的 DIP。此外，我们还证明，携带两个而不是一个 DI RNA 的 DIP 并不具有增强抑制 WT RNA 片段复制的能力。同样，两个 DI RNA 的存在也没有增强干扰素刺激基因 MxA 的诱导和 IAV 感染的抑制。总的来说，我们的研究结果表明，来自编码聚合酶亚基的基因组片段的多个 DI RNA 的存在可能不会导致抗病毒活性的增强。
