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

被引：2

作者：

Jorfi, Samireh ^{[1
]}

Ansa-Addo, Ephraim Abrokwa ^{[1
,7
]}

Mariniello, Katia ^{[1
,8
]}

Warde, Purva ^{[2
]}

Senian, Ahmad Asyraf bin ^{[2
,9
]}

Stratton, Dan ^{[3
]}

Bax, Bridget E. ^{[4
]}

Levene, Michelle ^{[4
]}

Lange, Sigrun ^{[5
,6
]}

Inal, Jameel Malhador ^{[1
,2
]}

机构：

[1] London Metropolitan Univ, Cell Commun Dis Pathol, Sch Human Sci, London N7 8DB, England

[2] Univ Hertfordshire, Sch Life & Med Sci, Biosci Res Grp, Hatfield AL10 9EU, England

[3] Open Univ, Sch Life Hlth & Chem Sci, Milton Keynes MK7 6AA, England

[4] St Georges Univ London, Mol & Clin Sci Res Inst, London SW17 0RE, England

[5] Univ Westminster, Sch Life Sci, Tissue Architecture & Regenerat Res Grp, 116, New Cavendish St, London, England

[6] UCL, Sch Pharm, Brunswick Sq, London, England

[7] Ohio State Univ, Pelotonia Inst Immuno Oncol, Columbus, OH 43210 USA

[8] Queen Mary Univ London, William Harvey Res Inst, London, England

[9] Sarawak Gen Hosp, Clin Res Ctr, Kuching, Malaysia

来源：

JOURNAL OF GENERAL VIROLOGY | 2023年 / 104卷 / 09期

关键词：

coxsackievirus B1; extracellular vesicles; nonlytic transmission; RICE-DWARF-VIRUS; PROTEIN-KINASE-C; INDUCED APOPTOSIS; MICROVESICLES; MACROPINOCYTOSIS; ACTIVATION; B3; EXOSOMES; SPREAD; ENTRY;

D O I：

10.1099/jgv.0.001884

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页数：20