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

Research output: Contribution to JournalArticleAcademicpeer-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 languageEnglish
Pages (from-to)119-132
Number of pages14
JournalJournal of Biological Physics
Volume44
Issue number2
Early online date15 Dec 2017
DOIs
Publication statusPublished - Jun 2018

Fingerprint

adenoviruses
Human Adenoviruses
Protein Precursors
Capsid
mutations
Point Mutation
proteins
viruses
gene therapy
vaccines
Viruses
Active Immunotherapy
Proteins
Atomic Force Microscopy
crosslinking
nanoindentation
Life Cycle Stages
Genetic Therapy
therapy
deoxyribonucleic acid

Keywords

  • Adenovirus
  • Atomic force microscopy
  • Force spectroscopy
  • Mechanical properties
  • Nanoindentation
  • Protein VI

Cite this

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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.",
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A single point mutation in precursor protein VI doubles the mechanical strength of human adenovirus. / van Rosmalen, Mariska G.M.; Nemerow, Glen R.; Wuite, Gijs J.L.; Roos, Wouter H.

In: Journal of Biological Physics, Vol. 44, No. 2, 06.2018, p. 119-132.

Research output: Contribution to JournalArticleAcademicpeer-review

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