Mechanosensitive extrusion of Enterovirus A71-infected cells from colonic organoids. 2023

Jasmine Moshiri, and Ailsa R Craven, and Sara B Mixon, and Manuel R Amieva, and Karla Kirkegaard
Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.

Enterovirus A71 causes severe disease upon systemic infection, sometimes leading to life-threatening neurological dysfunction. However, in most cases infection is asymptomatic and limited to the gastrointestinal tract, where virus is amplified for transmission. Picornaviruses have previously been shown to exit infected cells via either cell lysis or secretion of vesicles. Here we report that entire Enterovirus A71-infected cells are specifically extruded from the apical surface of differentiated human colon organoids, as observed by confocal microscopy. Differential sensitivity to chemical and peptide inhibitors demonstrated that extrusion of virus-infected cells is dependent on force sensing via mechanosensitive ion channels rather than apoptotic cell death. When isolated and used as inoculum, intact virus-containing extruded cells can initiate new infections. In contrast, when mechanical force sensing is inhibited, large amounts of free virus are released. Thus, extrusion of live, virus-infected cells from intact epithelial tissue is likely to benefit both the integrity of host tissues and the protected spread of this faecal-oral pathogen within and between hosts.

UI MeSH Term Description Entries
D004769 Enterovirus Infections Diseases caused by ENTEROVIRUS. Infections, Enterovirus,Enterovirus Infection,Infection, Enterovirus
D004770 Enterovirus A genus of the family PICORNAVIRIDAE whose members preferentially inhabit the intestinal tract of a variety of hosts. The genus contains many species. Newly described members of human enteroviruses are assigned continuous numbers with the species designated "human enterovirus". Coxsackie Viruses,Coxsackieviruses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000956 Antigens, Viral Substances elaborated by viruses that have antigenic activity. Viral Antigen,Viral Antigens,Antigen, Viral
D014779 Virus Replication The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle. Viral Replication,Replication, Viral,Replication, Virus,Replications, Viral,Replications, Virus,Viral Replications,Virus Replications
D029821 Enterovirus A, Human A species of ENTEROVIRUS infecting humans and containing 10 serotypes, mostly coxsackieviruses. EV-A71,Enterovirus 71, Human,Human Enterovirus 71,Human Enterovirus A

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