Fusion of Large Polypeptides to Human Adenovirus Type 5 Capsid Protein IX Can Compromise Virion Stability and DNA Packaging Capacity.

Autor:	Poulin KL; Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada., McFall ER; Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.; Centre for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, Canada., Chan G; Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada., Provost NB; Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada., Christou C; Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada., Smith AC; Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada., Parks RJ; Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada rparks@ohri.ca.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.; Centre for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, Canada.; Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Jazyk:	angličtina
Zdroj:	Journal of virology [J Virol] 2020 Aug 17; Vol. 94 (17). Date of Electronic Publication: 2020 Aug 17 (Print Publication: 2020).
DOI:	10.1128/JVI.01112-20
Abstrakt:	The human adenovirus (HAdV) protein IX (pIX) is a minor component of the capsid that acts in part to stabilize the hexon-hexon interactions within the mature capsid. Virions lacking pIX have a reduced DNA packaging capacity and exhibit thermal instability. More recently, pIX has been developed as a platform for presentation of large polypeptides, such as fluorescent proteins or large targeting ligands, on the viral capsid. It is not known whether such modifications affect the natural ability of pIX to stabilize the HAdV virion. In this study, we show that addition of large polypeptides to pIX does not alter the natural stability of virions containing sub-wild-type-sized genomes. However, similar virions containing wild-type-sized genomes tend to genetically rearrange, likely due to selective pressure caused by virion instability as a result of compromised pIX function. IMPORTANCE Human adenovirus capsid protein IX (pIX) is involved in stabilizing the virion but has also been developed as a platform for presentation of various polypeptides on the surface of the virion. Whether such modifications affect the ability of pIX to stabilize the virion is unknown. We show that addition of large polypeptides to pIX can reduce both the DNA packaging capacity and the heat stability of the virion, which provides important guidance for the design of pIX-modified vectors. (Copyright © 2020 American Society for Microbiology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu