Receptor Recognition and Double-Membrane Vesicle Formation Mechanism of Animal Coronaviruses

Viruses rely on host proteins to complete their life cycles. CRISPR/Cas9 library screening serves as an efficient approach to identify key host factors essential for viral propagation. Our research group has systematically investigated the formation mechanism of double-membrane vesicles (DMVs) during the replication of porcine enteric coronaviruses. A series of critical host factors, including TMEM41B, ALG6, mLST8, DYRK1A and CLTC, have been successively identified. Further studies reveal that these factors participate in DMV formation and modulate coronavirus replication by regulating endoplasmic reticulum membrane remodeling, endoplasmic reticulum stress and autophagy, the mTORC1-ULK1 signaling pathway, viral RNA synthesis, and the utilization of autophagosome precursor membranes, respectively. This work confirms a conserved competitive relationship between autophagy-related membrane trafficking and the biogenesis of viral replication vesicles. Relevant findings have been published in journals such as Advanced Science, Cell Reports, mBio and Journal of Virology.