Adenoviruses enter their host cells by receptor-mediated endocytosis a
nd acid-activated penetration from endosomes into the cytosol and deli
ver their DNA genome into the nucleus. Our results show that incoming
adenovirus type 2 particles undergo a stepwise disassembly program nec
essary to allow progress of the virus in the entry pathway and release
of the genome into the nucleus. The fibers are released, the penton b
ase structures dissociated, the proteins connecting the DNA to the ins
ide surface of the capsid degraded or shed, and the capsid-stabilizing
minor proteins eliminated. The uncoating process starts immediately u
pon endocytic uptake with the loss of fibers and ends with the uptake
of dissociated hexon proteins and DNA into the nucleus.