A single point mutation in precursor protein VI doubles the mechanical strength of human adenovirus

Mariska G.M. van Rosmalen; Glen R. Nemerow; Gijs J.L. Wuite; Wouter H. Roos

doi:10.1007/s10867-017-9479-y

A single point mutation in precursor protein VI doubles the mechanical strength of human adenovirus

Mariska G.M. van Rosmalen, Glen R. Nemerow, Gijs J.L. Wuite^*, Wouter H. Roos

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Viruses are extensively studied as vectors for vaccine applications and gene therapies. For these applications, understanding the material properties of viruses is crucial for creating optimal functionality. Using atomic force microscopy (AFM) nanoindentation, we studied the mechanical properties of human adenovirus type 5 with the fiber of type 35 (Ad5F35) and compared it to viral capsids with a single point mutation in the protein VI precursor protein (pVI-S28C). Surprisingly, the pVI-S28C mutant turned out to be twice as stiff as the Ad5F35 capsids. We suggest that this major increase in strength is the result of the DNA crosslinking activity of precursor protein VII, as this protein was detected in the pVI-S28C mutant capsids. The infectivity was similar for both capsids, indicating that mutation did not affect the ability of protein VI to lyse the endosomal membrane. This study highlights that it is possible to increase the mechanical stability of a capsid even with a single point mutation while not affecting the viral life cycle. Such insight can help enable the development of more stable vectors for therapeutic applications.

Original language	English
Pages (from-to)	119-132
Number of pages	14
Journal	Journal of Biological Physics
Volume	44
Issue number	2
Early online date	15 Dec 2017
DOIs	https://doi.org/10.1007/s10867-017-9479-y
Publication status	Published - Jun 2018

Funding

Acknowledgements This work was funded by the Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO) through NWO Vidi (to W.H.R.) and Vici (to G.J.L.W.) grants, the Stichting voor Fundamenteel Onderzoek der Materie (FOM) through Projectruimte grants (to G.J.L.W. and W.H.R.) and by NIH R21AI112714 (to G.N. and W.H.R.). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Funders	Funder number
National Institutes of Health	R21AI112714
Stichting voor Fundamenteel Onderzoek der Materie
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Foundation for Fundamental Research on Matter

Keywords

Adenovirus
Atomic force microscopy
Force spectroscopy
Mechanical properties
Nanoindentation
Protein VI

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "A single point mutation in precursor protein VI doubles the mechanical strength of human adenovirus",

abstract = "Viruses are extensively studied as vectors for vaccine applications and gene therapies. For these applications, understanding the material properties of viruses is crucial for creating optimal functionality. Using atomic force microscopy (AFM) nanoindentation, we studied the mechanical properties of human adenovirus type 5 with the fiber of type 35 (Ad5F35) and compared it to viral capsids with a single point mutation in the protein VI precursor protein (pVI-S28C). Surprisingly, the pVI-S28C mutant turned out to be twice as stiff as the Ad5F35 capsids. We suggest that this major increase in strength is the result of the DNA crosslinking activity of precursor protein VII, as this protein was detected in the pVI-S28C mutant capsids. The infectivity was similar for both capsids, indicating that mutation did not affect the ability of protein VI to lyse the endosomal membrane. This study highlights that it is possible to increase the mechanical stability of a capsid even with a single point mutation while not affecting the viral life cycle. Such insight can help enable the development of more stable vectors for therapeutic applications.",

keywords = "Adenovirus, Atomic force microscopy, Force spectroscopy, Mechanical properties, Nanoindentation, Protein VI",

author = "{van Rosmalen}, {Mariska G.M.} and Nemerow, {Glen R.} and Wuite, {Gijs J.L.} and Roos, {Wouter H.}",

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AU - Roos, Wouter H.

PY - 2018/6

Y1 - 2018/6

N2 - Viruses are extensively studied as vectors for vaccine applications and gene therapies. For these applications, understanding the material properties of viruses is crucial for creating optimal functionality. Using atomic force microscopy (AFM) nanoindentation, we studied the mechanical properties of human adenovirus type 5 with the fiber of type 35 (Ad5F35) and compared it to viral capsids with a single point mutation in the protein VI precursor protein (pVI-S28C). Surprisingly, the pVI-S28C mutant turned out to be twice as stiff as the Ad5F35 capsids. We suggest that this major increase in strength is the result of the DNA crosslinking activity of precursor protein VII, as this protein was detected in the pVI-S28C mutant capsids. The infectivity was similar for both capsids, indicating that mutation did not affect the ability of protein VI to lyse the endosomal membrane. This study highlights that it is possible to increase the mechanical stability of a capsid even with a single point mutation while not affecting the viral life cycle. Such insight can help enable the development of more stable vectors for therapeutic applications.

AB - Viruses are extensively studied as vectors for vaccine applications and gene therapies. For these applications, understanding the material properties of viruses is crucial for creating optimal functionality. Using atomic force microscopy (AFM) nanoindentation, we studied the mechanical properties of human adenovirus type 5 with the fiber of type 35 (Ad5F35) and compared it to viral capsids with a single point mutation in the protein VI precursor protein (pVI-S28C). Surprisingly, the pVI-S28C mutant turned out to be twice as stiff as the Ad5F35 capsids. We suggest that this major increase in strength is the result of the DNA crosslinking activity of precursor protein VII, as this protein was detected in the pVI-S28C mutant capsids. The infectivity was similar for both capsids, indicating that mutation did not affect the ability of protein VI to lyse the endosomal membrane. This study highlights that it is possible to increase the mechanical stability of a capsid even with a single point mutation while not affecting the viral life cycle. Such insight can help enable the development of more stable vectors for therapeutic applications.

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A single point mutation in precursor protein VI doubles the mechanical strength of human adenovirus

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