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

doi:10.1099/jgv.0.001884

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

J Gen Virol. 2023 Sep;104(9). doi: 10.1099/jgv.0.001884.

Authors

Samireh Jorfi¹, Ephraim Abrokwa Ansa-Addo^{1

2}, Katia Mariniello^{1

3}, Purva Warde⁴, Ahmad Asyraf Bin Senian^{4

5}, Dan Stratton⁶, Bridget E Bax⁷, Michelle Levene⁷, Sigrun Lange^{8

9}, Jameel Malhador Inal^{1

4}

Affiliations

¹ Cell Communication in Disease Pathology, School of Human Sciences, London Metropolitan University, London N7 8DB, UK.
² Present address: Pelotonia Institute for Immuno-Oncology, The James, Ohio State University, Columbus, OH 43210, USA.
³ Present address: William Harvey Research Institute, Queen Mary, University of London, London, UK.
⁴ Biosciences Research Group, School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9EU, UK.
⁵ Present address: Clinical Research Centre, Sarawak General Hospital, Kuching, Malaysia.
⁶ School of Life, Health & Chemical Sciences, The Open University, Milton Keynes MK7 6AE, UK.
⁷ Molecular and Clinical Sciences Research Institute, St. George's, University of London, London SW17 0RE, UK.
⁸ Tissue Architecture and Regeneration Research Group, School of Life Sciences, University of Westminster, 116, New Cavendish St., London, UK.
⁹ University College London School of Pharmacy, Brunswick Sq., London, UK.

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 (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.

Keywords: coxsackievirus B1; extracellular vesicles; nonlytic transmission.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis*
Cell Death
Extracellular Vesicles*
HeLa Cells
Humans
RNA, Small Interfering

Substances

RNA, Small Interfering