Mechanics of Viral Chromatin Reveals the Pressurization of Human Adenovirus.

TitleMechanics of Viral Chromatin Reveals the Pressurization of Human Adenovirus.
Publication TypeJournal Article
Year of Publication2015
AuthorsOrtega-Esteban, A, Condezo, GN, Pérez-Berná, AJ, Chillón, M, S Flint, J, Reguera, D, San Martín, C, de Pablo, PJ
JournalACS Nano
Volume9
Issue11
Pagination10826-33
Date Published2015 Nov 24
ISSN1936-086X
KeywordsAdenoviruses, Human, Capsid, Chromatin, Entropy, HEK293 Cells, HeLa Cells, Humans, Pressure, Spermidine, Virion
Abstract

<p>Tight confinement of naked genomes within some viruses results in high internal pressure that facilitates their translocation into the host. Adenovirus, however, encodes histone-like proteins that associate with its genome resulting in a confined DNA-protein condensate (core). Cleavage of these proteins during maturation decreases core condensation and primes the virion for proper uncoating via unidentified mechanisms. Here we open individual, mature and immature adenovirus cages to directly probe the mechanics of their chromatin-like cores. We find that immature cores are more rigid than the mature ones, unveiling a mechanical signature of their condensation level. Conversely, intact mature particles demonstrate more rigidity than immature or empty ones. DNA-condensing polyamines revert the mechanics of mature capsid and cores to near-immature values. The combination of these experiments reveals the pressurization of adenovirus particles induced by maturation. We estimate a pressure of ∼30 atm by continuous elasticity, which is corroborated by modeling the adenovirus mini-chromosome as a confined compact polymer. We propose this pressurization as a mechanism that facilitates initiating the stepwise disassembly of the mature particle, enabling its escape from the endosome and final genome release at the nuclear pore.</p>

DOI10.1021/acsnano.5b03417
Alternate JournalACS Nano
PubMed ID26491879