Recently, Prof. Peng Guiqing's team, in collaboration with Prof. Xie Shengsong, identified mLST8, as a key host factor required for coronavirus replication. The research results were published in the international microbiology journal mBio entitled “mLST8 is essential for coronavirus replication and regulates its replication through the mTORC1 pathway
Coronaviruses can “use” and “hijack” host factors to regulate the intracellular environment during replication, so it is urgent to improve the understanding of virus-host interactions and to find targets for anti-coronaviral drugs. Coronaviruses invade the target cells of the host and build a “lair” (double membrane vesicles, DMVs) for efficient replication. In our previous study, we found that the host factor TMEM41B plays an important role in inducing the formation of double membrane vesicles (DMVs). However, the current metabolic pathways involved in coronavirus and the regulation of DMVs formation by key host factors are still not fully elucidated.
Our study identified a novel host factor, mLST8, that is essential for coronavirus replication. Knockout of mLST8 inhibited the mTORC1 signaling pathway, and it was verified that the mTORC1 but not the mTORC2 signaling pathway was essential for coronavirus replication. Further mechanistic studies revealed that reduced phosphorylation of ULK1, a factor downstream of mTORC1, promoted the activation of autophagy, which is responsible for antiviral replication in mLST8 KO cells. Transmission electron microscopy (TEM) indicated that both mLST8 KO and autophagy activator inhibited the formation of double membrane vesicles (DMVs) in early viral replication. It was also found that knockout of mLST8 and autophagy activator treatment also inhibited the replication of other coronaviruses (MHV, PDCoV), indicating a conserved relationship between autophagy activation and CoV replication. In summary, our work reveals that mLST8 is a novel host regulator of CoV replication, which provides new insights into the mechanism of CoV replication and can facilitate the development of broad-spectrum antiviral drugs.
The above work was carried out by Yanan Fu, a doctoral student of School of Animal Science and Technology,School of Animal Medicine, Huazhong Agricultural University, as the first author, and Prof. Guiqing Peng,Prof. Shengsong Xie, and Limeng Sun as the co-corresponding authors of the paper. The study was supported by the National Key Research and Development Program of China and the National Science Fund for Distinguished Young Scholars.
Link：https://doi.org/10.1128/mbio.00899-23
