Mechanics of Viral Chromatin Reveals the Pressurization of Human Adenovirus.
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.
Alvaro
A
Ortega-Esteban
Department of Macromolecular Structures and NanoBioMedicine Initiative, Centro Nacional de Biotecnología (CNB-CIC) , Darwin 3, 28049 Madrid, Spain.
Gabriela N
GN
Condezo
Department of Macromolecular Structures and NanoBioMedicine Initiative, Centro Nacional de Biotecnología (CNB-CIC) , Darwin 3, 28049 Madrid, Spain.
Ana J
AJ
Pérez-Berná
Institut Català de Recerca i Estudis Avançats (ICREA), CBATEG-Department of Biochemistry and Molecular Biology, Universitat Autonoma Barcelona , Bellaterra Barcelona, 08010, Spain.
Miguel
M
Chillón
Department of Molecular Biology, Princeton University , Princeton, New Jersey 08544, United States.
S Jane
SJ
Flint
Departament de Física Fonamental, Facultat de Física, Universitat de Barcelona , Martí i Franqués 1, 08028 Barcelona, Spain.
David
D
Reguera
Department of Macromolecular Structures and NanoBioMedicine Initiative, Centro Nacional de Biotecnología (CNB-CIC) , Darwin 3, 28049 Madrid, Spain.
Carmen
C
San Martín
Pedro J
PJ
de Pablo
D000260:Adenoviruses, Human / Q000737:chemistry*; D002213:Capsid / Q000737:chemistry*; D002843:Chromatin / Q000737:chemistry*; D019277:Entropy; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D011312:Pressure; D013095:Spermidine / Q000494:pharmacology; D014771:Virion / Q000737:chemistry*
D002843:Chromatin; D013095:Spermidine
DNA compaction; DNA−protein condensate; atomic force microscopy; force curve; nanoindentation; physical virology; viral mini-chromosome; virus core; virus maturation