The role of lysosomes as intermediates in betacoronavirus PHEV egress from nerve cells

J Virol. 2023 Dec 21;97(12):e0133823. doi: 10.1128/jvi.01338-23. Epub 2023 Nov 27.


Betacoronaviruses, including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and mouse hepatitis virus (MHV), exploit the lysosomal exocytosis pathway for egress. However, whether all betacoronaviruses members use the same pathway to exit cells remains unknown. Here, we demonstrated that porcine hemagglutinating encephalomyelitis virus (PHEV) egress occurs by Arl8b-dependent lysosomal exocytosis, a cellular egress mechanism shared by SARS-CoV-2 and MHV. Notably, PHEV acidifies lysosomes and activates lysosomal degradative enzymes, while SARS-CoV-2 and MHV deacidify lysosomes and limit the activation of lysosomal degradative enzymes. In addition, PHEV release depends on V-ATPase-mediated lysosomal pH. Furthermore, this is the first study to evaluate βCoV using lysosome for spreading through the body, and we have found that lysosome played a critical role in PHEV neural transmission and brain damage caused by virus infection in the central nervous system. Taken together, different betacoronaviruses could disrupt lysosomal function differently to exit cells.

Keywords: CNS; PHEV; V-ATPase; betacoronaviruses; lysosome; virus egress.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Betacoronavirus 1* / metabolism
  • Coronavirus Infections* / pathology
  • Coronavirus Infections* / transmission
  • Coronavirus Infections* / virology
  • Exocytosis*
  • Hydrogen-Ion Concentration
  • Lysosomes* / enzymology
  • Lysosomes* / metabolism
  • Lysosomes* / virology
  • Mice
  • Murine hepatitis virus / metabolism
  • Neurons* / enzymology
  • Neurons* / metabolism
  • Neurons* / pathology
  • Neurons* / virology
  • SARS-CoV-2 / metabolism
  • Swine / virology
  • Vacuolar Proton-Translocating ATPases / metabolism


  • Vacuolar Proton-Translocating ATPases