Читать книгу Principles of Virology - Jane Flint, S. Jane Flint - Страница 245

Adenoviruses comprise a double-stranded DNA genome packaged in an icosahedral capsid (Chapter 4). Adenovirus uncoating is a sequential, multistep process that was determined using multiple techniques that include live-cell, atomic force, and cryo-electron microscopy and X-ray crystallography. Internalization of most adenovirus serotypes by receptor-mediated endocytosis requires attachment of viral fibers to an Ig-like cell surface receptor and binding of the penton base to a second cell receptor, an integrin (Fig. 5.5). Uncoating begins with this initial attachment; the interaction of two viral capsid proteins with two different receptors promotes the dissociation of the fiber from the capsid and disrupts its structure. Additionally, it has been proposed that the interaction with multiple integrin molecules might induce conformational changes to the penton base. Uncoating continues as the virus particle is transported via the endosomes from the cell surface toward the nuclear membrane (Fig. 5.21). Endosome acidification promotes the release of protein VI, which induces disruption of the endosomal membrane, thereby delivering the remainder of the particle into the cytoplasm. An N-terminal amphipathic α-helix of protein VI is probably responsible for disrupting the membrane in a pH-dependent manner. Like the fusion peptides of class I fusion proteins, this region of the protein is exposed following cleavage during particle maturation and appears to be masked in the native capsid by the hexon protein until capsid destabilization. The liberated subviral particle then docks onto the nuclear pore complex, where uncoating is completed (see “Nuclear Import of DNA Genomes” below).

Figure 5.20 Entry of Semliki Forest virus into cells. Semliki Forest virus enters cells by clathrin-dependent receptor-mediated endocytosis, and membrane fusion is catalyzed by acidification of late endosomes. Fusion results in the exposure of nucleocapsid to the cytoplasm. Cellular ribosomes bind and disassemble the capsid, rendering the viral RNA accessible to translation. Adapted from Marsh M, Helenius A. 1989. Adv Virus Res 36:107–151, 1989, with permission.