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

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 language	English
Article number	001884
Journal	Journal of General Virology
Volume	104
Issue number	9
DOIs	https://doi.org/10.1099/jgv.0.001884
Publication status	Published - 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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Accepted_Version
© 2023 The Authors. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1099/jgv.0.001884
Accepted author manuscript, 2.19 MBLicence: CC BY

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Jorfi, S., Ansa-Addo, E. A., Mariniello, K., Warde, P., Bin Senian, A. A., Stratton, D., Bax, B. E., Levene, M., Lange, S., & Inal, J. M. (2023). A Coxsackievirus B1-mediated nonlytic Extracellular Vesicle-to-cell mechanism of virus transmission and its possible control through modulation of EV release. Journal of General Virology, 104(9), Article 001884. https://doi.org/10.1099/jgv.0.001884

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

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

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

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Jorfi, S, Ansa-Addo, EA, Mariniello, K, Warde, P, Bin Senian, AA, Stratton, D, Bax, BE, Levene, M, Lange, S & Inal, JM 2023, 'A Coxsackievirus B1-mediated nonlytic Extracellular Vesicle-to-cell mechanism of virus transmission and its possible control through modulation of EV release', Journal of General Virology, vol. 104, no. 9, 001884. https://doi.org/10.1099/jgv.0.001884

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T1 - A Coxsackievirus B1-mediated nonlytic Extracellular Vesicle-to-cell mechanism of virus transmission and its possible control through modulation of EV release

AU - Jorfi, Samireh

AU - Ansa-Addo, Ephraim Abrokwa

AU - Mariniello, Katia

AU - Warde, Purva

AU - Bin Senian, Ahmad Asyraf

AU - Stratton, Dan

AU - Bax, Bridget E

AU - Levene, Michelle

AU - Lange, Sigrun

AU - Inal, Jameel Malhador

PY - 2023/9/4

Y1 - 2023/9/4

N2 - 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.

AB - 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.

KW - Humans

KW - HeLa Cells

KW - Apoptosis

KW - Cell Death

KW - Extracellular Vesicles

KW - RNA, Small Interfering

KW - coxsackievirus B1

KW - extracellular vesicles

KW - nonlytic transmission

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U2 - 10.1099/jgv.0.001884

DO - 10.1099/jgv.0.001884

M3 - Article

C2 - 37665326

SN - 0022-1317

VL - 104

JO - Journal of General Virology

JF - Journal of General Virology

IS - 9

M1 - 001884

ER -

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

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Keywords

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