MERS-CoV nsp1 regulates autophagic flux via mTOR signalling and dysfunctional lysosomes.
Yujie FengZhaoyi PanZhihui WangZhengyang LeiSongge YangHuajun ZhaoXueyao WangYating YuQiuju HanJian ZhangPublished in: Emerging microbes & infections (2022)
Autophagy, a cellular surveillance mechanism, plays an important role in combating invading pathogens. However, viruses have evolved various strategies to disrupt autophagy and even hijack it for replication and release. Here, we demonstrated that Middle East respiratory syndrome coronavirus (MERS-CoV) non-structural protein 1(nsp1) induces autophagy but inhibits autophagic activity. MERS-CoV nsp1 expression increased ROS and reduced ATP levels in cells, which activated AMPK and inhibited the mTOR signalling pathway, resulting in autophagy induction. Meanwhile, as an endonuclease, MERS-CoV nsp1 downregulated the mRNA of lysosome-related genes that were enriched in nsp1-located granules, which diminished lysosomal biogenesis and acidification, and inhibited autophagic flux. Importantly, MERS-CoV nsp1-induced autophagy can lead to cell death in vitro and in vivo . These findings clarify the mechanism by which MERS-CoV nsp1-mediated autophagy regulation, providing new insights for the prevention and treatment of the coronavirus.
Keyphrases
- respiratory syndrome coronavirus
- cell death
- sars cov
- cell cycle arrest
- coronavirus disease
- endoplasmic reticulum stress
- signaling pathway
- induced apoptosis
- oxidative stress
- cell proliferation
- dna repair
- public health
- long non coding rna
- small molecule
- smoking cessation
- antimicrobial resistance
- replacement therapy
- stress induced