Understanding Adenovirus maturation: A nanomechanics approach

D. Denning, S. Bennett, T. Mullen, C. Moyer, G. J. Wuite, G. Nemerow, W. H. Roos

Research output: Contribution to JournalMeeting AbstractAcademic

Abstract

The ability of adenoviruses to infect a broad range of species and tissues has led to a widespread interest in their biological functioning. However, there remains a big gap in our understanding of their assembly and maturation pathways. Here, we present AFM (Atomic Force Microscopy) nanoindentation and fatigue studies1,2 of adenovirus capsids3 at different stages of maturation. Surprisingly, we find that the intermediate (no DNA) immature capsid is mechanically indistinguishable as compared with the mature (DNA filled), suggesting a major stabilizing role of the scaffold protein.3 However, these capsids have distinctly different disassembly pathways, as indicated by a mechanically-induced fatigue analysis. Additionally, we observed that mutation of the protease cleavage site of the precursor protein VI yields a maturation-intermediate capsid, G33A, which has reduced infectivity and releases half as many pentons as the WT capsid. The presented results strongly indicate that the reduced infectivity results from a reduction in protein VI exposure, partially inhibiting lysis of the endosome and leading to abortive infection.
Original languageEnglish
Article numberSupplement 1
Pages (from-to)S184-S184
Number of pages1
JournalEuropean Biophysics Journal
Volume46
Publication statusPublished - Jul 2017

Cite this

Denning, D., Bennett, S., Mullen, T., Moyer, C., Wuite, G. J., Nemerow, G., & Roos, W. H. (2017). Understanding Adenovirus maturation: A nanomechanics approach. European Biophysics Journal, 46, S184-S184. [Supplement 1].
Denning, D. ; Bennett, S. ; Mullen, T. ; Moyer, C. ; Wuite, G. J. ; Nemerow, G. ; Roos, W. H. / Understanding Adenovirus maturation: A nanomechanics approach. In: European Biophysics Journal. 2017 ; Vol. 46. pp. S184-S184.
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abstract = "The ability of adenoviruses to infect a broad range of species and tissues has led to a widespread interest in their biological functioning. However, there remains a big gap in our understanding of their assembly and maturation pathways. Here, we present AFM (Atomic Force Microscopy) nanoindentation and fatigue studies1,2 of adenovirus capsids3 at different stages of maturation. Surprisingly, we find that the intermediate (no DNA) immature capsid is mechanically indistinguishable as compared with the mature (DNA filled), suggesting a major stabilizing role of the scaffold protein.3 However, these capsids have distinctly different disassembly pathways, as indicated by a mechanically-induced fatigue analysis. Additionally, we observed that mutation of the protease cleavage site of the precursor protein VI yields a maturation-intermediate capsid, G33A, which has reduced infectivity and releases half as many pentons as the WT capsid. The presented results strongly indicate that the reduced infectivity results from a reduction in protein VI exposure, partially inhibiting lysis of the endosome and leading to abortive infection.",
author = "D. Denning and S. Bennett and T. Mullen and C. Moyer and Wuite, {G. J.} and G. Nemerow and Roos, {W. H.}",
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Denning, D, Bennett, S, Mullen, T, Moyer, C, Wuite, GJ, Nemerow, G & Roos, WH 2017, 'Understanding Adenovirus maturation: A nanomechanics approach' European Biophysics Journal, vol. 46, Supplement 1, pp. S184-S184.

Understanding Adenovirus maturation: A nanomechanics approach. / Denning, D.; Bennett, S.; Mullen, T.; Moyer, C.; Wuite, G. J.; Nemerow, G.; Roos, W. H.

In: European Biophysics Journal, Vol. 46, Supplement 1, 07.2017, p. S184-S184.

Research output: Contribution to JournalMeeting AbstractAcademic

TY - JOUR

T1 - Understanding Adenovirus maturation: A nanomechanics approach

AU - Denning, D.

AU - Bennett, S.

AU - Mullen, T.

AU - Moyer, C.

AU - Wuite, G. J.

AU - Nemerow, G.

AU - Roos, W. H.

PY - 2017/7

Y1 - 2017/7

N2 - The ability of adenoviruses to infect a broad range of species and tissues has led to a widespread interest in their biological functioning. However, there remains a big gap in our understanding of their assembly and maturation pathways. Here, we present AFM (Atomic Force Microscopy) nanoindentation and fatigue studies1,2 of adenovirus capsids3 at different stages of maturation. Surprisingly, we find that the intermediate (no DNA) immature capsid is mechanically indistinguishable as compared with the mature (DNA filled), suggesting a major stabilizing role of the scaffold protein.3 However, these capsids have distinctly different disassembly pathways, as indicated by a mechanically-induced fatigue analysis. Additionally, we observed that mutation of the protease cleavage site of the precursor protein VI yields a maturation-intermediate capsid, G33A, which has reduced infectivity and releases half as many pentons as the WT capsid. The presented results strongly indicate that the reduced infectivity results from a reduction in protein VI exposure, partially inhibiting lysis of the endosome and leading to abortive infection.

AB - The ability of adenoviruses to infect a broad range of species and tissues has led to a widespread interest in their biological functioning. However, there remains a big gap in our understanding of their assembly and maturation pathways. Here, we present AFM (Atomic Force Microscopy) nanoindentation and fatigue studies1,2 of adenovirus capsids3 at different stages of maturation. Surprisingly, we find that the intermediate (no DNA) immature capsid is mechanically indistinguishable as compared with the mature (DNA filled), suggesting a major stabilizing role of the scaffold protein.3 However, these capsids have distinctly different disassembly pathways, as indicated by a mechanically-induced fatigue analysis. Additionally, we observed that mutation of the protease cleavage site of the precursor protein VI yields a maturation-intermediate capsid, G33A, which has reduced infectivity and releases half as many pentons as the WT capsid. The presented results strongly indicate that the reduced infectivity results from a reduction in protein VI exposure, partially inhibiting lysis of the endosome and leading to abortive infection.

M3 - Meeting Abstract

VL - 46

SP - S184-S184

JO - European Biophysics Journal

JF - European Biophysics Journal

SN - 0175-7571

M1 - Supplement 1

ER -

Denning D, Bennett S, Mullen T, Moyer C, Wuite GJ, Nemerow G et al. Understanding Adenovirus maturation: A nanomechanics approach. European Biophysics Journal. 2017 Jul;46:S184-S184. Supplement 1.