Institute of Virology Muenster (IVM), University Hospital Muenster (UKM), Muenster, Germany.
Section of Experimental Virology, Institute of Medical Microbiology, University Hospital Jena, Jena, Germany.
Cell Microbiol. 2021 Jun;23(6):e13323. doi: 10.1111/cmi.13323. Epub 2021 Mar 18.
Nonsense-mediated mRNA decay (NMD) was identified as a process to degrade flawed cellular messenger RNA (mRNA). Within the last decades it was also shown that NMD carries virus-restricting capacities and thus could be considered a part of the cellular antiviral system. As this was shown to affect primarily positive-sense single stranded RNA ((+)ssRNA) viruses there is only scarce knowledge if this also applies to negative-sense single stranded RNA ((-)ssRNA) viruses. Influenza A viruses (IAVs) harbour a segmented (-)ssRNA genome. During their replication IAVs produce numerous RNA transcripts and simultaneously impair cellular transcription and translation. The viral mRNAs hold several molecular patterns which can elicit NMD and in turn would lead to their degradation. This, in consequence, may mitigate viral propagation. Thus, we examined if a knockdown or a pharmacological inhibition of NMD key components may influence IAV replication. Additionally, we performed similar experiments with respiratory syncytial virus (RSV), another (-)ssRNA virus, but with a non-segmented genome. Although it seemed that a knockdown of up-frameshift protein 1 (UPF1), the central NMD factor, slightly increased viral mRNA and protein levels, no significant alteration of viral replication could be observed, implying that the NMD machinery may not have restricting capacities against (-)ssRNA viruses.
无意义介导的 mRNA 降解（NMD）被鉴定为一种降解有缺陷的细胞信使 RNA（mRNA）的过程。在过去的几十年中，也表明 NMD 具有限制病毒的能力，因此可以被认为是细胞抗病毒系统的一部分。由于这主要影响正单链 RNA（(+)ssRNA）病毒，因此对于负单链 RNA（(-)ssRNA）病毒是否也适用，知之甚少。甲型流感病毒（IAV）具有分段（-）ssRNA 基因组。在复制过程中，IAV 会产生大量 RNA 转录本，并同时损害细胞转录和翻译。病毒 mRNA 具有几种可以引发 NMD 的分子模式，进而导致它们的降解。这反过来可能会减轻病毒的传播。因此，我们研究了 NMD 关键成分的敲低或药理学抑制是否会影响 IAV 复制。此外，我们还对另一种（-）ssRNA 病毒呼吸道合胞病毒（RSV）进行了类似的实验，但它具有非分段基因组。尽管似乎中央 NMD 因子 UPF1 的敲低略微增加了病毒 mRNA 和蛋白水平，但没有观察到病毒复制的显著改变，这意味着 NMD 机制可能对（-）ssRNA 病毒没有限制能力。
