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

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

  • J Virol. 2023 Nov 27:e0133823. doi: 10.1128/jvi.01338-23.
Zhenzhen Wang # 1 Wenqi He # 1 Caili Li 1 Yuzhu Chen 1 Zi Li 1 Yubo Jiao 1 Jing Zhang 1 Junchao Shi 1 Gaili Wang 2 Jiyu Guan 1 Kui Zhao 1 Deguang Song 1 Feng Gao 1 Yungang Lan 1
Affiliations

Affiliations

  • 1 State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, Jilin, China.
  • 2 Jilin Academy of Animal Husbandry and Veterinary Medicine, Changchun, Jilin, China.
  • # Contributed equally.
Abstract

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.

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