Biogenesis of JC polyomavirus associated extracellular vesicles.

JC polyomavirus biogenesis extracellular vesicles

Journal

Journal of extracellular biology
ISSN: 2768-2811
Titre abrégé: J Extracell Biol
Pays: United States
ID NLM: 9918382980506676

Informations de publication

Date de publication:
May 2022
Historique:
entrez: 23 1 2023
pubmed: 24 1 2023
medline: 24 1 2023
Statut: ppublish

Résumé

JC polyomavirus (JCPyV) is a small, non-enveloped virus that persists in the kidney in about half the adult population. In severely immune-compromised individuals JCPyV causes the neurodegenerative disease progressive multifocal leukoencephalopathy (PML) in the brain. JCPyV has been shown to infect cells by both direct and indirect mechanisms, the latter involving extracellular vesicle (EV) mediated infection. While direct mechanisms of infection are well studied indirect EV mediated mechanisms are poorly understood. Using a combination of chemical and genetic approaches we show that several overlapping intracellular pathways are responsible for the biogenesis of virus containing EV. Here we show that targeting neutral sphingomyelinase 2 (nSMase2) with the drug cambinol decreased the spread of JCPyV over several viral life cycles. Genetic depletion of nSMase2 by either shRNA or CRISPR/Cas9 reduced EV-mediated infection. Individual knockdown of seven ESCRT-related proteins including HGS, ALIX, TSG101, VPS25, VPS20, CHMP4A, and VPS4A did not significantly reduce JCPyV associated EV (JCPyV(+) EV) infectivity, whereas knockdown of the tetraspanins CD9 and CD81 or trafficking and/or secretory autophagy-related proteins RAB8A, RAB27A, and GRASP65 all significantly reduced the spread of JCPyV and decreased EV-mediated infection. These findings point to a role for exosomes and secretory autophagosomes in the biogenesis of JCPyV associated EVs with specific roles for nSMase2, CD9, CD81, RAB8A, RAB27A, and GRASP65 proteins.

Identifiants

pubmed: 36688929
doi: 10.1002/jex2.43
pmc: PMC9854252
mid: NIHMS1864813
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : NINDS NIH HHS
ID : R01 NS043097
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS116836
Pays : United States

Déclaration de conflit d'intérêts

CONFLICT OF INTEREST DISCLOSURE No conflicts of interest are declared by the authors.

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Auteurs

Jenna Morris-Love (J)

Graduate Program in Pathobiology, Brown University, Providence, RI, USA.
Department of Molecular biology, Cellular Biology, and Biochemistry, Brown University, Providence, RI, USA.

Bethany A O'Hara (BA)

Department of Molecular biology, Cellular Biology, and Biochemistry, Brown University, Providence, RI, USA.

Gretchen V Gee (GV)

Department of Molecular biology, Cellular Biology, and Biochemistry, Brown University, Providence, RI, USA.
MassBiologics, University of Massachusetts Medical School, Fall River, MA, USA.

Aisling S Dugan (AS)

Department of Biology, Assumption University, Worcester, MA, USA.
Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, USA.

Ryan S O'Rourke (RS)

Graduate Program in Pathobiology, Brown University, Providence, RI, USA.
Department of Molecular biology, Cellular Biology, and Biochemistry, Brown University, Providence, RI, USA.

Brandon E Armstead (BE)

Graduate Program in Pathobiology, Brown University, Providence, RI, USA.

Benedetta Assetta (B)

Department of Molecular biology, Cellular Biology, and Biochemistry, Brown University, Providence, RI, USA.

Sheila A Haley (SA)

Department of Molecular biology, Cellular Biology, and Biochemistry, Brown University, Providence, RI, USA.

Walter J Atwood (WJ)

Department of Molecular biology, Cellular Biology, and Biochemistry, Brown University, Providence, RI, USA.

Classifications MeSH