Publication

Maturation of adenovirus primes the protein nano-shell for successful endosomal escape

Denning, D., Bennett, S., Mullen, T., Moyer, C., Vorselen, D., Wuite, G. J. L., Nemerow, G. & Roos, W. H., 15-Feb-2019, In : Nanoscale.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Denning, D., Bennett, S., Mullen, T., Moyer, C., Vorselen, D., Wuite, G. J. L., ... Roos, W. H. (2019). Maturation of adenovirus primes the protein nano-shell for successful endosomal escape. Nanoscale. https://doi.org/10.1039/c8nr10182e

Author

Denning, D ; Bennett, S ; Mullen, T ; Moyer, C ; Vorselen, D ; Wuite, G J L ; Nemerow, G ; Roos, W H. / Maturation of adenovirus primes the protein nano-shell for successful endosomal escape. In: Nanoscale. 2019.

Harvard

Denning, D, Bennett, S, Mullen, T, Moyer, C, Vorselen, D, Wuite, GJL, Nemerow, G & Roos, WH 2019, 'Maturation of adenovirus primes the protein nano-shell for successful endosomal escape' Nanoscale. https://doi.org/10.1039/c8nr10182e

Standard

Maturation of adenovirus primes the protein nano-shell for successful endosomal escape. / Denning, D; Bennett, S; Mullen, T; Moyer, C; Vorselen, D; Wuite, G J L; Nemerow, G; Roos, W H.

In: Nanoscale, 15.02.2019.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Denning D, Bennett S, Mullen T, Moyer C, Vorselen D, Wuite GJL et al. Maturation of adenovirus primes the protein nano-shell for successful endosomal escape. Nanoscale. 2019 Feb 15. https://doi.org/10.1039/c8nr10182e


BibTeX

@article{f92c509c406c45bdbbe51b077bd74aa1,
title = "Maturation of adenovirus primes the protein nano-shell for successful endosomal escape",
abstract = "The ability of adenoviruses to infect a broad range of species has spurred a growing interest in nanomedicine to use adenovirus as a cargo delivery vehicle. While successful maturation of adenovirus and controlled disassembly are critical for efficient infection, the underlying mechanisms regulating these processes are not well understood. Here, we present Atomic Force Microscopy nanoindentation and fatigue studies of adenovirus capsids at different maturation stages to scrutinize their dynamic uncoating properties. Surprisingly, we find that the early intermediate immature (lacking DNA) capsid is mechanically indistinguishable in both break force and spring constant from the mature (containing DNA) capsid. However, mature and immature capsids do display distinct disassembly pathways, as revealed by our mechanically-induced fatigue analysis. The mature capsid first loses the pentons, followed by either long-term capsid stability or abrupt and complete disassembly. However, the immature capsid has a stable penton region and undergoes a stochastic disassembly mechanism, thought to be due to the absence of genomic pressure. Strikingly, the addition of the genome alone is not sufficient to achieve penton destabilization as indicated by the penton stability of the maturation-intermediate mutant, G33A. Full penton destabilization was achieved only when the genome was present in addition to the successful maturation-linked proteolytic cleavage of preprotein VI. Therefore these findings strongly indicate that maturation of adenovirus in concert with genomic pressure induces penton destabilization and thus, primes the capsid for controlled disassembly. This latter aspect is critical for efficient infection and successful cargo delivery.",
author = "D Denning and S Bennett and T Mullen and C Moyer and D Vorselen and Wuite, {G J L} and G Nemerow and Roos, {W H}",
year = "2019",
month = "2",
day = "15",
doi = "10.1039/c8nr10182e",
language = "English",
journal = "Nanoscale",
issn = "2040-3364",
publisher = "ROYAL SOC CHEMISTRY",

}

RIS

TY - JOUR

T1 - Maturation of adenovirus primes the protein nano-shell for successful endosomal escape

AU - Denning, D

AU - Bennett, S

AU - Mullen, T

AU - Moyer, C

AU - Vorselen, D

AU - Wuite, G J L

AU - Nemerow, G

AU - Roos, W H

PY - 2019/2/15

Y1 - 2019/2/15

N2 - The ability of adenoviruses to infect a broad range of species has spurred a growing interest in nanomedicine to use adenovirus as a cargo delivery vehicle. While successful maturation of adenovirus and controlled disassembly are critical for efficient infection, the underlying mechanisms regulating these processes are not well understood. Here, we present Atomic Force Microscopy nanoindentation and fatigue studies of adenovirus capsids at different maturation stages to scrutinize their dynamic uncoating properties. Surprisingly, we find that the early intermediate immature (lacking DNA) capsid is mechanically indistinguishable in both break force and spring constant from the mature (containing DNA) capsid. However, mature and immature capsids do display distinct disassembly pathways, as revealed by our mechanically-induced fatigue analysis. The mature capsid first loses the pentons, followed by either long-term capsid stability or abrupt and complete disassembly. However, the immature capsid has a stable penton region and undergoes a stochastic disassembly mechanism, thought to be due to the absence of genomic pressure. Strikingly, the addition of the genome alone is not sufficient to achieve penton destabilization as indicated by the penton stability of the maturation-intermediate mutant, G33A. Full penton destabilization was achieved only when the genome was present in addition to the successful maturation-linked proteolytic cleavage of preprotein VI. Therefore these findings strongly indicate that maturation of adenovirus in concert with genomic pressure induces penton destabilization and thus, primes the capsid for controlled disassembly. This latter aspect is critical for efficient infection and successful cargo delivery.

AB - The ability of adenoviruses to infect a broad range of species has spurred a growing interest in nanomedicine to use adenovirus as a cargo delivery vehicle. While successful maturation of adenovirus and controlled disassembly are critical for efficient infection, the underlying mechanisms regulating these processes are not well understood. Here, we present Atomic Force Microscopy nanoindentation and fatigue studies of adenovirus capsids at different maturation stages to scrutinize their dynamic uncoating properties. Surprisingly, we find that the early intermediate immature (lacking DNA) capsid is mechanically indistinguishable in both break force and spring constant from the mature (containing DNA) capsid. However, mature and immature capsids do display distinct disassembly pathways, as revealed by our mechanically-induced fatigue analysis. The mature capsid first loses the pentons, followed by either long-term capsid stability or abrupt and complete disassembly. However, the immature capsid has a stable penton region and undergoes a stochastic disassembly mechanism, thought to be due to the absence of genomic pressure. Strikingly, the addition of the genome alone is not sufficient to achieve penton destabilization as indicated by the penton stability of the maturation-intermediate mutant, G33A. Full penton destabilization was achieved only when the genome was present in addition to the successful maturation-linked proteolytic cleavage of preprotein VI. Therefore these findings strongly indicate that maturation of adenovirus in concert with genomic pressure induces penton destabilization and thus, primes the capsid for controlled disassembly. This latter aspect is critical for efficient infection and successful cargo delivery.

U2 - 10.1039/c8nr10182e

DO - 10.1039/c8nr10182e

M3 - Article

JO - Nanoscale

JF - Nanoscale

SN - 2040-3364

ER -

ID: 76582766