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

Samireh Jorfi, Ephraim Abrokwa Ansa-Addo, Katia Mariniello, Purva Warde, Ahmad Asyraf Bin Senian, Dan Stratton, Bridget E Bax, Michelle Levene, Sigrun Lange, Jameel Malhador Inal

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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 (CVB1 i-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 CVB1 i-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 CVB1 i-mEVs; EV release may also prevent apoptosis of infected cells whilst spreading apoptosis to secondary sites of infection.
Original languageEnglish
JournalJournal of General Virology
Volume104
Issue number9
DOIs
Publication statusPublished - 4 Sept 2023

Keywords

  • Humans
  • HeLa Cells
  • Apoptosis
  • Cell Death
  • Extracellular Vesicles
  • RNA, Small Interfering
  • coxsackievirus B1
  • extracellular vesicles
  • nonlytic transmission

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