A Coxsackievirus B1-mediated nonlytic Extracellular Vesicle-to-cell mechanism of virus transmission and its possible control through modulation of EV release

Jorfi S 1 , Ansa-Addo EA 1 , Mariniello K 1 , Warde P 2 , Bin Senian AA 2 , Stratton D 3 Show all authors , Bax BE 4 , Levene M 4 , Lange S 5 , Inal JM 1

Affiliations 

  • 1 Cell Communication in Disease Pathology, School of Human Sciences, London Metropolitan University, London N7 8DB, UK
  • 2 Biosciences Research Group, School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9EU, UK
  • 3 School of Life, Health & Chemical Sciences, The Open University, Milton Keynes MK7 6AE, UK
  • 4 Molecular and Clinical Sciences Research Institute, St. George's, University of London, London SW17 0RE, UK
  • 5 Tissue Architecture and Regeneration Research Group, School of Life Sciences, University of Westminster, 116, New Cavendish St., London, UK
J Gen Virol, 2023 Sep;104(9).
PMID: 37665326 DOI: 10.1099/jgv.0.001884

Abstract

Like most non-enveloped viruses, CVB1 mainly uses cell lysis to spread. Details of a nonlytic virus transmission remain unclear. Extracellular Vesicles (EVs) transfer biomolecules between cells. We show that CVB1 entry into HeLa cells results in apoptosis and release of CVB1-induced 'medium-sized' EVs (CVB1i-mEVs). These mEVs (100-300 nm) harbour CVB1 as shown by immunoblotting with anti-CVB1-antibody; viral capsids were detected by transmission electron microscopy and RT-PCR revealed CVB1 RNA. The percentage of mEVs released from CVB1-infected HeLa cells harbouring virus was estimated from TEM at 34 %. Inhibition of CVB1i-mEV production, with calpeptin or siRNA knockdown of CAPNS1 in HeLa cells limited spread of CVB1 suggesting these vesicles disseminate CVB1 virions to new host cells by a nonlytic EV-to-cell mechanism. This was confirmed by detecting CVB1 virions inside HeLa cells after co-culture with CVB1i-mEVs; EV release may also prevent apoptosis of infected cells whilst spreading apoptosis to secondary sites of infection.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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