Читать книгу Principles of Virology - Jane Flint, S. Jane Flint - Страница 253

The capsids of many DNA-containing viruses are larger than 39 nm in diameter and cannot be imported into the nucleus from the cytoplasm. One mechanism for crossing the nuclear membrane comprises docking of a capsid onto the nuclear pore complex, followed by delivery of the viral DNA into the nucleus. Adenoviral and herpesviral DNAs are transported into the nucleus via this mechanism, albeit with different strategies. Herpes simplex virus capsids dock onto the nuclear pore, where they remain largely intact, and the nucleic acid is injected into the nucleus through a portal in the nucleocapsid (Fig. 5.26B). The DNA of some bacteriophages is packaged in virus particles at high pressure, which provides sufficient force to insert the viral DNA genome into the bacterial cell (Box 5.6). A similar mechanism may allow injection of herpesviral DNA. Herpesvirus capsids also dock onto the nuclear pore complex, and interaction with nucleoporins destabilizes a viral protein, pUL25, which locks the genome inside the capsid. This event drives the naked viral DNA, which is packaged in the nucleocapsid under very high pressure, to exit through the portal. Ordinarily, the charged, hydrophilic viral nucleic acid would have difficulty passing through the pore, but this mechanism overcomes the requirement for hydrophobic interactions with nucleoporins.

In contrast to herpesvirus particles, partially disassembled adenovirus capsids dock onto the nuclear pore complex by interaction with NUP214 (Fig. 5.26C and 5.27). Release of the viral genome requires capsid protein binding to kinesin-1, the motor protein that mediates transport on microtubules from the nucleus to the cell periphery. As the capsid is held on the nuclear pore, movement of kinesin-1 toward the plasma membrane is thought to pull the capsid apart (Fig. 5.27). The released protein VII-associated viral DNA is then imported into the nucleus, where viral transcription begins.

The 26-nm capsid of parvoviruses is small enough to fit through the nuclear pore (39 nm), and it has been assumed that these virus particles enter by this route. However, there is no experimental evidence that parvovirus capsids pass intact through the nuclear pore. Instead, virus particles bind to the nuclear pore complex, followed by disruption of the nuclear envelope and the nuclear lamina, leading to entry of virus particles (Fig. 5.26D). After release from the endoplasmic reticulum, the 45-nm capsid of simian virus 40 also docks onto the nuclear pore, initiating disruption of the nuclear envelope and lamina. Such nuclear disruption appears to require cell proteins that also participate in the increased nuclear permeability that takes place during mitosis, raising the possibility that nuclear entry of these viral genomes is a consequence of remodeling a cellular process.